1.

Hemostasis
2. Pengertian perdarahan sebagai kompliasi, kapan dapat dikatakan sebagai komplikasi
3. Macam-macam perdarahan
4. Pengertian antikoagulan, direct oral anti coagulant dan macam-macam
5. Heparin, bagaimana penggunaannya, bridging heparin
6. Atrial fibrilasi
7. Kapan dihentikan antikoagulan sebelum pencabutan dan kapan dimulai diminum lagi
8. Pemeriksaan apa saja yang diperlukan sebelum pencabutan pada pasien dengan direct
anti coagulant dan bridging heparin
Pembahasan:
1. cara penanganan perdarahan pada pasien dengan direct anticoagulant dan bridging
heparin
2. Obat dan cairan apa yang boleh dan tidak boleh digunakan
3. Pencegahan perdarahan saat tindakan pencabutan

Perdarahan
Perdarahan adalah keadaan darah keluar dari pembuluh darah. Perdarahan mungkin
merupakan komplikasi yang paling ditakuti, karena oleh dokter maupun pasiennya dianggap
mengancam kehidupan. Bermacam-macam tes laboratorium bisa mengkonfirmasikan masalah
untuk mengidentifikasi bagian khusus yang menyebabkan kegagalan mekanisme pembekuan
darah.(Pedersen,1996)
Menurut Archer (1961) penyebab perdarahan abnormal dapat terjadi secara mekanis dan
biokimiawi.

1. Perdarahan Mekanis
Perdarahan mekanis yaitu perdarahan yang berasal dari berbagai ukuran pembuluh darah
yang terluka yang tak dapat berhenti karena jendelan darah tidak dapat terbentuk atau
karena jendelan darah yang sudah terjadi pecah atau lepas dari ujung pembuluh yang
terbuka. Biasanya disebabkan karena ukuran pembuluh darah dan kecepatan darah (arteri
dan vena), atau karena jumlah pembuluh darah kecil dan trauma pasca operasi yang
dirterima oleh kapiler. Contohnya perdarahan pada ekstraksi gigi, insisi jaringan lunak.
(Mangunkusumo, 1997)
A. Perdarahan Primer
Pada penderita normal, setelah prosedur bedah dan penutupan luka dalam rongga
mulut selesai, perdarahan biasanya secara spontan akan behenti (perdarahan primer).
Bila pendarahan primer ini tidak berhenti 4-5 menit setelah akhir operasi atau
ekstraksi gigi, maka lakukanlah pemerikasaan control perdarahan sebelum pasien
pulang.
Merupakan komplikasi yang dapat mempengaruhi kesehatan pasien dengan serius,
terutama ketika berlanjut untuk beberapa jam. Kehilangan darah dapat menurunkan
kesehatan pasien sehingga memudahkan penderita terkena infeksi.
Di dalam rongga mulut perdarahan primer dapat berasal dari tulang maupun jaringan
lunak.
Perawatan local perdarahan primer
1) Perdarahan tulang
Cara menghentikannya :
 Mengambil instrument yang tumpul dan menekan tulang sekeliling ke dalam
titik perdarahan. Dengan cara ini arteri akan terhimpit tulang, lumen menjadi
sempit dan aliran darah menjadi tertahan sehingga ada kesempatan darah
menjendal
 Mengoleskan lilin-tulang (Bone-wax) kedalam lumen pembuluh darah
 Kapiler dalam tulang yang mengalami perdarahan oozing dapat berhenti baik
secara spontan maupun saat lapisan mukoperiosteal dijahit kembali diatas
prosesus alveolaris
 Bila perdarahan melimpah soket gigi ditekan dengan kain kasa selama 5-10
menit. Setelah itu kasa diambil lalu diganti dengan lembaran gel foam di
setiap lubang dalam soket gigi sebelum melakukan penjahitan jaringan
kembali pada posisi semula.
 Bila dalam operasi digunakan anestesi local yang dicampur dengan larutan
vasokonstriktor, maka harus diingat bahwa pengeluaran darah tidak akan
terlihat jelas dan soket harus diamati secara seksama untuk mencegah
pengeluaran darah bila kerja vasokonstriktor pengaruhnya telah berakhir.
 Untuk reposisi tulang yang mengalami fraktur tipe greenstick diusahakan
dengan menekan tulang dengan cara kompresi manual.
(Mangunkusumo, 1997)
2) Perdarahan jaringan lunak
Cara menghentikannya :
 Jahitan jaringan lunak digunakan untuk perdarahan kapiler.
Menggunakan tekanan. Bila perdarahan masih berlangsung, gunakan tekanan
dengan gulungan kain kasa pada daerah perdarahan dan pertahankan di
tempat itu dalam waktu 5-10 menit. Lalu bila perdarahan sudah berhenti
tambahkan gulungan kain kasa untuk memberi tekanan tambahan di tempat
 perdarahan tersebut. Rahang atas dan bawah saling dikatupakan kuat-kuat
dan keadaan itu dipertahankan dengan bantuan perban elastic yang dipasang
melingkari kepala dan mandibula untuk waktu beberapa jam.
(Mangunkusumo, 1997)
Penanganan awal apabila terjadi perdarahan arteri adalah dengan penekanan.
Penekanan diperoleh dari penekanan langsung dengan jari atau dengan kain
kasa.( Pedersen,1996 )
 Ligasi pembuluh darah. Pada perdarahan arteri jaringan lunak, pembuluh
darah harus dipegang dengan hemostat dan diikat dengan ikatan langsung
atau dengan penggunaan jahitan sirkumferensial sekeliling jaringan lunak.
Ligasi tidak dapat dilakukan untuk perdarahan karena luka tusuk pada
pembuluh darah. Perdarahan karena luka jenis ini dapat dihentikan dengan
bimanual ( satu tangan di dalam dan satu tangan diuar mulut )
Ligasi dapat dilakukan pada 3 tempat yaitu :
 Arteri lingualis pada triangulus Lesser
 Arteri karotis eksterna di leher antara cabang tiroideus superior dan
cabang lingualis
 Arteri karotis eksterna di leher daerah retromandibular sebelah lateral
ligamentum stilomandibular.
Pemilihan ligasi tergantung dari tempat terjadinya perdarahan tersebut.
(Mangunkusumo, 1997)
 Elektokoagulasi : didasarkan atas koagulasi darah dengan aplikasi panas
yang menghasilkan retraksi jaringan pada masa nekrosis.(Fragiskos,2007)

Fig. Clamping of a branch of the palatine artery Fig. Diagrammatic illustration showing steps
in a with a hemostat to controlthe hemorrhaging the ligation of the palatine artery after
severance.
a Severance of the vessel.
b Vessel clamped by a hemostat.
c Ligationwith a resorbable suture

B. Perdarahan Berulang ( Intermediate atau Recurrent )

 Adalah perdarahan yang terjadi dalam waktu 24 jam setelah operasi selesai. Penyebab
perdarahan berulang adalah :
a. Selama operasi berlangsung tekanan darah menurun karena penderita mengalami
keadaan semi syok. Ketika penderita kembali siuman, tekanan darah akan kembali
normal sehingga terjadi perdarahan lagi.
b. Ligasi terlepas
c. Penderita melepas bantalan yang digunakan untuk menekan perdarahan sehingga
tekanan darah menghancurkan jendelan darah yang sudah terjadi dan terjadi
perdarahan berulang.
(Mangunkusumo, 1997)

C. Perdarahan Sekunder
Adalah perdarahan yang terjadi setelah 24 jam. Perdarahan ini terjadi karena jendelan
darah yang yang telah terjadi hancur atau lepas karena suatu proses infeksi.
Perawatannya adalah :
 Bila jahitan mengendur saat masih terpengaruh anestesi local, daerah perdarahan
dijahit beranyaman.
 Daerah perdarahan ditekan dengan kain kasa atau menggunakan bahan cetak
(compound) yang sebelumnya dilunakkan lebih dulu. Kemudian penderita
diintruksikan untuk menggigitnya dengan maksud mendapat cetakan daerah
perdarahan. Tunggu sampai cetakan compound mengeras dan sedikit demi sedikit
bagian yang lebih dikurangi. Bagian cetakan yang masih kasar dihaluskan
kemudian cetakan siap digunakan pada penderita dengan menggigitnya sampai
perdarahan dapat diatasi.
 Pada daerah perdarahan diaplikasikan langsung dengan larutan vasokonstriktor,
misalnya epinefrin. Epinefrin diteteskan pada spon yang dapat menyempitkan
lumen pembuluh darah sehingga darah mempunyai kesempatan untuk menjendal.
 Aplikasi bahan secara local untuk mempercepat penjendalan darah misalnya
thrombin, fibrogen local, thromboplastin local. Caranya bahan diteteskan pada
spon lalu diletakkan diatas daerah perdarahan atau dimasukkan ke dalam soket
gigi.
(Mangunkusumo, 1997)
 Fig. Packing of the alveolus with hemostatic
materials: gelatin sponge, collagen, etc.

D. Perdarahan akibat trauma instrumentasi

Perdarahan ini berasal dari kesalahan instrumentasi saat operasi termasuk eksodonsia
gigi seperti :
a. Gerakan manipulasi ekstraksi gigi yang secara tidak sadar menyebabkan engsel
forsep menjepit bibir.
b. Ekstraksi gigi molar mandibula posterior dimana mulut forsep menjepit jaringan
lunak di sebelah lingual.
c. Separasi jaringan mukosa gingival yang tidak sempurna dari gigi yang akan
diekstraksi.
d. Tergelincirnya elevator sehingga melukai daerah jaringan lunak dan membentuk
luka yang dalam dan perdarahan yang parah.
e. Perdarahan pada kasus odontektomi molar mandibula ketiga.
(Mangunkusumo, 1997)
2. Perdarahan biokimiawi
Perdarahan biokimiawi adalah abnormalitas elemen darah atau sistem vaskular
yang menghambat pembentukan jendelan darah dan organisasi darah normal. Perdarahan
biokimiawi ditemui pada hemophilia, gangguan hepar, dan kelainan darah, hipertensi,
dan infeksi jaringan seperti pada pyorrhoe alveolaris. (Mangunkusumo, 1997)
Perdarahan biokimiawi adalah perdarahan yang disebabkan karena satu atau lebih
factor penjendalan darah yang normal tidak ada. ( Archer, 1961 )

Perdarahan biokimiawi dapat :

 Bersifat bawaan sejak lahir ( genetically condition disorder )
 Didapat setelah lahir ( acquired ) yaitu sebagai akibat dari penyakit yang diderita
atau melalui sebab penggunaan obat-obatan yang mengganggu pembentukan
elemen yang berguna untuk penjendalan darah.
Substansi yang berperan dalam penjendalan darah antara lain :
 a. factor platelet yang berasal dari disintegrasi platelet.
b. Anti Hemofilik Globulin ( AHG )
c. Plasma Thromboplastin Complement ( PTC ), kekurangan factor ini akan
menimbulkan Christmas disease yang secara klinis dan genetis gejala yang
ditimbulkan hampir sama dengan hemophilia ,klasik.
d. Plasma Thrombopastin Anteccedent ( PTA ), kekurangan factor ini akan
menimbulkan gejala yang mirip dengan hemofili. Dapat terjadi pada laki-laki
maupun perempuan.
e. Hageman Faktor ( HF ), tanpa HF akan terjadi hambatan pembentukan
thromboplastin secara klinis tidak disertai dengan gejala defek hemofili.
f. Thromboplastin, dibentuk dari interaksi factor-faktor 1 sampai 5 bersama
dengan kalsium.
g. Prothrombin, merupakan suatu protein kompleks yang disintesa di dalam hati
dan proses pembentukannya membutuhkan vitamin K.
h. Factor V ( Proaccelerin ), factor ini berfungsi untuk membantu mengubah
prothrombin menjadi thrombin. Tanpa factor ini akan menimbulkan penyakit
parahemofilia.
i. Factor VII ( Proconvertin ), factor ini juga berperan untuk membantu
mengubah prothrombin menjadi thrombin. Factor VII akan berkurang bila
diberi obat-obatan anti koagulan.
j. Kalsium, penting dalam pembentukan thromboplastin dan thrombin.
k. Thrombin, dibentuk oleh prothrombin + thromboplastin + factor V + factor
VII
l. Fibrinogen, disintesis di dalam hati
m. Fibrinolisin, merupakan suatu substansi yang diaktifkan dari profibrinolisin
yang menyebabkan lisisnya jendelan darah. Fibrinolisis naik pada keadaan
patologis tertentu ( pada prostatic carcinoma, myelositik leukemia, luka bakar
parah, dan syok ).
(Mangunkusumo, 1997)
Perawatan dan kontrol perdarahan ekstraksi gigi
Bourgoyne ( 1949 ) menyatakan ada 2 masalah yang harus diatasi, yaitu :
1. Perdarahan pada jaringan lunak selama dan sesudah ekstraksi gigi
Bila perdarahan terjadi pada pembuluh darah arteri yang besar, sebaiknya melakukan
ligature arteri. Bila tipe perdarahan hanya oozing kapiler maka hemostasis dapat
dilakukan dengan menekankan kain kasa yang telah dibasahi adrenalin dengan
perbandingan 1:1000 pada luka. Selama operasi hemostasis dilakukan dengan
menekankan kain kasa kering / hangat pada pembuluh darah. Pertolongan pertama pada
perdarahan di daerah muka dapat dilakukan dengan member tekanan dengan perban
diatas daerah yang berdarah, yang biasanya dilakukan pada titik-titik tekanan dari
pembuluh darah yang terkena.
 2. Perawatan perdarahan pasca ekstraksi gigi dengan menggunaakan asam tannic dan
adrenalin klorida
Bila terjadi komplikasi laserasi gingival maka dilakukan jahitan terlebih dahulu tapi soket
jangan sampai tertutup sama sekali. Jangan sekali-sekali memasukkan pack ke dalam
soket gigi, karena bila pack telah penuh darah akan memyebabkan gingival sobek
kembali. Kain kasa dibasahi dengan 10% asam tannic, mekanisme kerja sama dengan
penggunaan adrenalin klorida 1:1000.

DAFTAR PUSTAKA

Archer, W. Harry, 1961, Oral Surgery, 3rd edition, W.B. Saunders Co., Philadelphia
Bourgoyne, J.R., 1949, Surgery of The Mouth and Jaws, Dental Items of Interest Publishing Co.,
Brooklyn New York
Andreasen, J.O., Andrease F.M., Andersson, L., 2007, Textbook and colour Atlas of Traumatic
Injuries to The Teeth, 4th edition, Blackwell Publishing Ltd., Oxford

Fagiskos, F.D., 2007, Oral Surgery, Springer, Berlin

Mangunkusumo, Haryono, 1997, Eksodonsia dan Komplikasinya, laboratorium Bedah Mulut FK

UGM, Yogyakarta

Pedersen, Gordon W., 1996, Buku Ajar Praktis Bedah Mulut, EGC, Jakarta

Wray, D., et al, 2003, Textbook of General and Oral Surgery, Churchill Livingstone, London

A. Macam-macam perdarahan dan penanganannya

PERDARAHAN MEKANIS

1. Perdarahan primer
Pada penderita normal, setelah prosedur bedah dan penutupan luka dalam rongga mulut
selesai, perdarahan biasanya secara spontan akan berhenti. Bila perdarahn primer ini tidak
berhenti 4-5menit setelah akhir operasi atau ekstraksi gigi, sebelum penderita
dipulangkan lakukan control perdarahan. Di dalam rongga mulut, perdarahan primer ini
dapat berasal dari tulang maupun jaringan lunak.

(Archer,1975)
PERAWATAN LOKAL PERDARAHAN PRIMER

a. Perdarahan tulang. Cara menghentikannya:

 Mengambil instrument yang tumpul dan melindas tulang sekeliling ke dalam
titik perdarahan. Dengan cara ini arteri akan terhimpit tulang, lumen menjadi
sempit, dan aliran darah menjadi tertahan, sehingga ada kesempatan darah
menjendal.
 Mengoleskan lilin-tulang (bone-wax) ke dalam lumen pembuluh darah.
 Kapiler dalam tulang yang mengalami perdarahan oozing dapat berhenti baik
secara spontan maupun saat lapisan mukoperiosteal dijahit kembali di atas
processus alveolaris.
 Bila perdarahan melimpah, soket gigi ditekan dengan kain kasa selama 5-
10menit. Setelah itu kain kasa diambil lalu diganti dengan lembaran gel foam
di setiap lubang dalam soket gigi sebelum melakukan penjahitan jaringan
kembali pada posisi semula.
 Bila dalam operasi digunakan anestesi local yang dicampur dengan larutan
vasokonstriktor (epinefrin), maka harus diingat bahwa pancaran darah tidak
akan terlihat jelas dan soket harus diamati secara seksama untuk mencegah
pancaran darah bila kerja vasokonstriktor pengaruhnya telah berakhir.
 Untuk reposisi tulang yang mengalami fraktur tulang tipe greenstick ini,
usahakan dengan menekan tulang melalui cara kompresi manual.
b. Perdarahan jaringan lunak
Cara menghentikannya:

 Jahitan jaringan lunak. Perdarahan kapiler jaringan lunak pada saat operasi
baik dihentikan dengan jahitan.
 Tekanan. Bila perdarahan masih berlangsung, gunakan tekanan gulungan kain
kasa pada daerah perdarahan dan pertahankan pada tempat itu untuk waktu 5-
10menit. Lalu bila perdarahan sudah berhenti, tambahan gulungan kain kasa
diperlukan untuk memberi tekanan tambahan di tempat perdarahan tersebut.
Rahang atas dan rahang bawah dikatupkan kuat-kuat dan keadaan itu
 dipertahankan dengan bantuan perban elastic yang dipasang melingkari kepala
dan mandibula untuk waktu beberapa jam.
 Ligasi pembuluh darah. Pada perdarahan arteri jaringan lunak, pembuluh
darah harus dipegang dengan hemostat dan diikat, dapat dengan ikatan
langsung atau dengan penggunaan jahitan sirkumferensial sekeliling jaringan
lunak. Menurut Archer (1975), ligasi dapat dilakukan pada 3 tempat yaitu
pada :
1) Arteri lingualis pada triangulus Lasser
2) Arteri karotis eksterna pada leher antara cabang a. thyroideus superior dan
A. lingualis.
3) Arteri karotis eksterna di daerah retromandibular sebelah lateral
ligamentum stylomandibula.
(Archer, 1975)

2. Perdarahan berulang (intermediet/recurrent)

Perdarahan berulang adalah perdarahan yang terjadi dalam waktu 24 jam setelah operasi.
Penyebab perdarahan berulang:

a. Saat operasi berlangsung tekanan darah pasien kemungkinan turun karena semi-
shock, lalu tekanan darah kembali normal seiring dengan masa penyembuhan pasien,
kemudian terjadi perdarahan yang disebut recurrent hemorrhage.
b. Ligasi terlepas
c. Penderita melepas bantalan yang digunakan untuk menekan perdarahan saat tidur
sehingga tekanan darah menghancurkan jendalan darah yang sudah terjadi dan tidak
telindungi spon penghenti perdarahan.
(Archer, 1975)

3. Perdarahan sekunder
Perdarahan sekunder adalah perdarahan yang terjadi setelah 24 jam.

Penyebabnya karena jendalan darah yang telah terjadi hancur atau lepas karena suatu
proses infeksi.

PERAWATAN PERDARAHAN SEKUNDER

 Dapat digunakan salah satu atau kombinasi dari beberapa cara di bawah ini:

a) Bila jahitan mengendor, di bawah anestesi lokal, daerah perdarahn dijahit beranyam.
b) Daerah perdarahan ditekan dengan kain kasa atau menggunakan bahan cetak
(compound) yang sebelumnya dilunakkan lebih dahulu lalu digunakan, daerah
perdarahan diblok dengan bahan itu. Kemudian penderita diinstruksikan untuk
menggigitnya dengan maksud mendapat cetakan daerah perdarahan. Tunggu sampai
cetakan compound mengeras dan sedikit demi sedikit bagian yang berlebih dikurangi.
Bagian cetakan yang masih kasar dihaluskan. Cetakan siap digunakan pendeerita
dengan menggigitnya sampai perdarahan dapat diatasi.
c) Pada daerah perdarahan diaplikasi langsung dengan larutan vasokonstriktor (misalnya
epinefrin). Epinefrin diteteskan pada spons yang berpengaruh menyempitkan lumen
pembuluh darah sehingga darah mempunyai kesempatan untuk menjendal.
d) Aplikasi bahan secara lokal dengan maksud untuk mempercepat penjendalan darah
(misalnya thrombin, fibrogen lokal, thromboplastin lokal). Cara : bahan diteteskan
pada spons lalu diletakkan di atas daerah perdarahan atau dimasukkan ke dalam soket
gigi.
(Mangunkusumo,1997)

PERDARAHAN BIOKIMIAWI

Perdarahan biokimiawi adalah perdarahan yang disebabkan karena tidak adanya satu atau
lebih faktor penjendalan darah yang normal (Archer,1975).

Perdarahan ini dapat bersifat:

a. Bawaan semenjak lahir (genetically condition disorders)

b. Didapat setelah lahir (Acquired), yaitu sebagai akibat dari penyakit yang diderita atau
melalui sebab penggunaan obat-obatan yang mengganggu pembentukan elemen yang
berguna untuk penjendalan darah.
(Archer,1975)
 Sebagian besar substansi yang terlibat dalam mekanisme penjendalan darah adalah
protein kompleks.

Substansi yang sudah dikenal sebagai faktor yang ikut dalam penjendalan darah yaitu:

1) Faktor platelet, yang berasal dari disintegrasi platelet.

2) Anti-hemophilic globulin (AHG), tanpa AHG akan menimbulkan hemofili yang sudah
lama dikenal yang secara genetis “sex-linked” dibawa oleh wanita tetapi hanya dapat
terjadi pada laki-laki.
3) Plasma thromboplastin component (PTC), tanpa PTC akan menimbulkan “Chrismast
disease” yaitu secara klinis dan genetis hamper sama dengan gejala-gejala yang
ditimbulkan oleh hemofili yang klasik.
4) Plasma thromboplastin antecedent (PTA), tanpa PTA akan menimbulkan gejala-gejala
yang hamper sama dengan hemofili tetapi dapat terjadi baik pada laki-laki maupun
perempuan.
5) Faktor Hageman (HF), tanpa adanya HF maka pembentukan thromboplastin terhalangi.
6) Thromboplastin, dibentuk oleh interaksi faktor I-V bersama dengan kalsium.
7) Prothrombin, adalah suatu suatu protein yang disintesa di dalam hati.
8) Faktor V (Proaccelerin), membantu dalam perubahan prothrombin menjadi thrombin.
9) Faktor VII (Proconvertin), juga membantu dalam perubahan prothrombin menjadi
thrombin.
10) Kalsium, sangat penting untuk pembentukan thromboplastin dan thrombin.
11) Thrombin, dibentuk oleh prothrombin + thromboplastin + faktor V + faktor VII.
12) Fibrinogen, merupakan protein lain yang disintesa dalam hati.
13) Fibrinolisin, adalah suatu substansi yang diaktifkan dari profibrinolisin yang
menyebabkan lisis jendalan darah.
(Mangunkusumo,1997)

Perdarahan akibat trauma instrumentasi

Perdarahan ini berasal dari kesalahan instrumentasi saat dilakukan eksodonsi gigi, dapat
terjadi karena :
 a. Saat melakukan gerakan manipulasi ekstraksi gigi, secara tidak sadar engsel forcep
menjepit bibir.
b. Saat ekstrasi gigi molar mandibula posterior terkadang mulut forcep menjepit jaringan
lunak di sebelah lingual yang menjadi bagian dari jaringan dasar mulut.
c. Separasi jaringan mukosa ginggivadari gigi yang akan diekstrasi terkadang dilakukan
tidak sempurna, sehingga ekstrasi gigi yang dilakukan akan berakibat laserasi
jaringan mukosa dan akan terjadi perdarahan.
d. Elevator saat digunakan dapat tergelincir dan melukaii daerah jaringan lunak dan
membentuk luka yang dalam dan perdarahan yang parah
(Mangunkusumo,1997)

Archer, H.W., 1975, Oral and Maxillofacial Surgery, Volume One, 5th edition, W. B. Saunders
Company, Philadelphia.

Archer, H.W., 1975, Oral and Maxillofacial Surgery, Volume Two, 5th edition, W. B. Saunders
Company, Philadelphia.

Fragiskos, F.D., 2007, Oral Surgery, Springer, New York.

Gans, J. B., 1972, Atlas of Oral Surgery, Mosby Company, Missouri.

Mangunkusumo, H., 1997, Eksodonsia dan Komplikasinya, FKG UGM, Yogyakarta.

Pedersen, G. W., 1996, Buku Ajar Praktis Bedah Mulut, EGC, Jakarta.

Wray D., et al, 2003, Textbook of General and Oral Surgery, Churchill Livingstone, Edinburgh.

ANTIKOAGULAN
Pengertian
Antikoagulan adalah adalah zat yang mencegah penggumpalan darah dengan cara mengikat
kalsium atau dengan menghambat pembentukan trombin yang diperlukan untuk mengkonversi
fibrinogen menjadi fibrin dalam proses pembekuan.
1. Warfarin (Coumadin)
Warfarin beraksi pada hati menghambat vitamin K untuk sintesis factor VII, IX, X dan II
(protrombin). Vitamin K dapat diadministrasikan sebagai antidotum perdarahan, namun
sintesis factor pengganti memerlukan 24-72 jam (Kudsi, 2012). Hemorarge yang parah
memerlukan transfusi. Warfarin kontraindikasi pada pasien yang hamil karena dapat
melewati dinding plasenta yang menyebabkan hemorarge fetal atau intrauterine yang
berhubungan dengan malformasi fetal. Warfarin digunakan untuk mengurangi resiko
tromboembolisme, termasuk stroke atau transient ischemic attacks (Becker, 2013).
2. Heparin
Antikoagulan ini tidak merubah fungsi hati dalam sistesis factor pembekuan darah.
Heparin merupakan asam mukopolisacharida yang bekerja dengan cara menghentikan
factor Xa sehingga menghambat pembentukan trombin dari prothrombin sehingga
menghentikan pembentukan fibrin dari fibrinogen sehingga cara kerjanya berdaya seperti
antitombin dan antitromboplastin. Heparin dapat diadministrasikan secara subkutan atau
intravena. Efek samping dari antikoagulan ini selain hemorarge adalah trombositopenia.
Hal ini berhubungan dengan reaksi immune-mediated dimana antibody terbentuk untuk
mencegah pembentukan kompleks yang terbentuk oleh heparin dan produk platelet
disebut factor platelet. (Becker, 2013)
Mekanisme kerja heparin yaitu dengan berikatan dengan antitrombin III, inhibitor
protease yang berkompleks dengan faktor penggumpalan darah yang aktif yaitu
faktor II, IX, X, dan XI.
 Mengubah cara pembentukan AT III
 Memapar sisi aktif AT III
 Mempercepat pembentukan kompleks AT III-protease
 Melepaskan heparin, faktor penggumpalan yang aktif berikatan dengan AT
III
 Indikasi penggunaan heparin
1. Mencegah pembentukan thrombus (thromboprophylaxis selama pembedahan)
2. Mencegah thrombus yang berkepanjangan
3. Mencegah thrombosis pada sirkulasi ekstracorporeal (missal pada hemodialisa)
4. Perawatan angina
A textbook of clinical pharmacology and therapeutics

Kudsi Z, 2012, Management of Bleeding Disorders in the Dental Practice: Managing

Patients on Anticoagulants. Dent Update 39:358-363
Becker DE, 2013, Antithrombotic Drgus: Pharmacology and Implications for Dental
Practice, Anesth Prog 60:72-80

3. Dabigatran
Menghambat aktivitas IIa.
Indikasi penggunaan dabigatran adalah fibrilasi atrium, yaitu mencegah pembentukan
thrombin karena irama jantung yang tidak teratur.
4. Rivaroxaban
Menghambat aktivitas Xa
5. Apixaban
Apixaban merupakan inhibitor faktot Xa yang berfungsi menghambat pembentikan
thrombus pada pasien dengan atrial fibrilasis
6. Enoxaparin
Menghambat aktivitas Xa dan IIa.
Merupakan propilaksis pada kelainan tromboemboli pada vena, pencegahan thrombosis
sirkulasi ekstracorporeal selama hemodialisa, serta perawatan thrombosis vena.
7. Dalteparin
Menghambat aktivitas Xa dan IIa
Dalteparin merupakan indikasi untuk deep vein thrombosis (DVT) dan menvegah
komplikasi pembuluh darah pada penderita angina.antikoagulan ini memiliki efek
samping berupa efek hematologis (hemorarge dan trombositopenia).
8. Fondaparinux
 Menghambat aktivitas Xa.
Fondaparinux merupakan pentasakarida sintetis yang mengikat dan menghambat factor
Xa. Fondaparinux efektif dalam mencegah tromboembilisme vena dan embolisme
pulmonary. Pada sindrom coronary akut, fondaparinux dapat mengurangi efek iskemik.
Fondaprinux dapat diadministrasikan secara injeksi subkutan
9. Bivalirudin
Menghambat aktivitas IIa
10. Hirudin
Hirudin merupakan antikoagulan yang dapat disintesis dalam teknologi DNA
rekombinan. Hirudin merupakan penghambat langsung thrombin dan lebih spesifik
daripada heparin. Hirudin dapat menghambat clot-associated thrombin dan tidak
tergantug pada antitrombin III.

MANAJEMEN PERIOPERATIF PADA PASIEN DENGAN TERAPI

ANTIKOAGULAN DAN ANTIPLATELET

A. Manajemen Perioperatif Pasien dengan Terapi Antikoagulan

American College of Chest Physicians (ACCP) merekomendasikan guideline untuk
manajemen antikoagulan pasien dalam kategori risiko berdasarkan indikasi dan lama pemakaian
termasuk adanya katup jantung buatan, riwayat fibrilasi atrium, atau riwayat tromboemboli vena
(VTE) (Jaffer, 2009).
 Bridging anticoagulation (bridge therapy) merupakan pemberian sementara unfractioned
heparin secara intravena (IV UFH) atau low-molecular weight heparin (LMWH) sebelum
tindakan bedah. ACCP merekomendasikan pasien berdasarkan risiko terjadinya tromboemboli.

 Risiko tinggi – bridging antikoagulasi dengan LMWH subkutan atau IV UFH dengan
dosis terapetik
 Risiko sedang – bridging antikoagulasi dengan LMWH subkutan atau IV UFH dosis
terapetik, atau LMWH subkutan dosis rendah
 Risiko rendah – bridging antikoagulasi dengan LMWH subkutan dosis rendah atau
tanpa bridging
(Jaffer, 2009)

Sebelum dilakukan bridging therapy, perlu diidentifikasi apakah pasien membutuhkan

bridging therapy sebelum melakukan operasi/ bedah tertentu (Jaffer, 2009).
 (Jaffer, 2009)

Menurut Jaffer (2009), protokol terapi bridging antikoagulan adalah sebagai berikut.

Preoperasi

- Warfarin dihentikan 5 hari sebelum pembedahan (menghentikan 4 dosis) jika INR

preoperasi berkisar antara 2-3, atau 6 hari sebelum pembedahan (menghentikan 5 dosis)
jika INR preoperasi berkisar antara 3-4,5.
- Untuk bridge therapy, LMWH yang digunakan adalah enoxaparin 1 mg/kg BB atau
dalteparin 100 IU/kg BB melalui subkutan setiap 12 jam. LMWH mulai diberikan 36 jam
setelah diberikan dosis terakhir warfarin.
- Dosis terakhir LMWH diberikan sekitar 24 jam sebelum pembedahan
Pascaoperasi
- Untuk bedah minor, LMWH mulai diberikan kembali dengan dosis penuh sekitar 24 jam
pascaoperasi. Untuk bedah mayor dan untuk pasien dengan risiko perdarahan tinggi,
digunakan dosis profilaktik pada 2 hari pertama pascaoperasi.
- Warfarin diberikan kembali 1 hari pascaoperasi.
- INR dan prothrombin time diperiksa setiap hari sampai mencapai angka terapetik.
- LMWH dihentikan jika INR sudah berkisar antara 2-3 selama 2 hari berturut-turut.

(Kraai et al., 2009)

Secara umum, terapi warfarin dihentikan sebelum melakukan berbagai prosedur

pembedahan, termasuk bedah minor. Akan tetapi menurut Jaffer (2009), beberapa prosedur aman
dilakukan tanpa penghentian pemberian warfarin jangka panjang.

International normalized ratio (INR) merupakan nilai yang menunjukkan efektivitas

penggunaan terapi antikoagulan pada pasien secara akurat. INR dihitung dari perbandingan
antara prothrombin time (PT) pasien dengan PT kontrol yang dipangkatkan dengan International
sensitivity index value (ISI). Pasien dengan sistem koagulasi normal memiliki INR 1,0 (Hirsh
dan Poller, 1994). Idealnya INR diukur 24 jam sebelum dilakukan tindakan, akan tetapi pada
pasien yang memiliki INR stabil, pengukuran INR 72 jam sebelum prosedur masih dapat
diterima. Pada pasien dengan terapi antikoagulan, biasanya INR berkisar antara 2,0-4,0
tergantung alasan penggunaan antikoagulan (Dinkova et al., 2013). Nilai INR yang optimal
untuk prosedur bedah dental adalah 2,5 karena angka tersebut menunjukkan risiko minimal
terjadinya tromboemboli dan hemoragi. Akan tetapi prosedur bedah dental minor aman
dilakukan pada INR 2,0-4,0, disertai dengan kontrol perdarahan Pasien dengan INR lebih dari
4,0 sebaiknya tidak dilakukan tindakan bedah sampai dilakukan kontrol terapi antikoagulannya
(Pototski dan Amenabar, 2007).

Prosedur Dental dan Manajemen Antikoagulan

Menurut Madan (2005), prosedur bedah minor dental seperti pencabutan sederhana sampai
tiga gigi, bedah gingiva, prosedur mahkota-jaket, scaling supragingiva, dan pencabutan gigi
dengan pembedahan dapat dilakukan tanpa mengubah dosis medikasi baik antikoagulan maupun
antiplatelet. Jika akan dilakukan pencabutan lebih dari tiga gigi maka pencabutan dilakukan pada
beberapa kali kunjungan dan pada setiap kunjungan dilakukan pencabutan 2-3 gigi dalam satu
kuadran.

Bleeding risk Types of Procedures Recommendations

Low risk  Crown and bridge procedures  Do not interupt warfarin
 Multiple simple extractions therapy
 Periodontal exams, x-ray  Use local measures to
 Regional and local injections prevent or control bleeding
anesthetics  Consider other dental
 Restorations options if concerned: Limit
 Standard root canal 2-3 teeth (non-impacted,
 Sub-gingival scaling with inflamed bony or soft tissue)
gums estractions per dental
 Supra-gingival scaling, root planing, appointment
endodontics  Restrict scaling to one
 Surgical removal of teeth quadrant per visit and re-
assess
Moderate risk  Alveoloplasties  Same as above
 Apicoectomy (root removal)  Use extra caution
 Alveolar surgery (bone removal)
 Dental implants
 Full mouth extractions
High risk  Extensive surgery  Consider patient’s risk for
 Tori removal thromboembolic event. If
 Vestibuloplasty low, then may consider
 Free gingival graft adjusting warfarin dose
 Block bone graft  If risk of
thromboembolism is high,
then discuss with dentist
 and PCP. May consider
adjusting warfarin dose.

B. Manajemen Perioperatif Pasien dengan Terapi Antiplatelet

Pasien yang diberikan terapi antiplatelet adalah pasien dengan coronary stent yang apabila
terapi dihentikan dapat meningkatkan risiko terjadinya trombosis. Risiko trombosis pada pasien
dengan stent meningkat terutama pada periode pascaoperasi, terlebih jika pembedahan dilakukan
segera setelah pemasangan stent (Jaffer, 2009).
Manajemen perioperatif yang optimal pada pasien dengan stent arteri koroner bergantung
pada beberapa faktor, di antaranya tipe stent, lama implantasi stent, lokasi setiap stent pada
sirkulasi koroner, komplikasi revaskularisasi, riwayat trombosis stent, obat antiplatelet yang
digunakan, dan lain-lain (Jaffer, 2009). Menurut Lecompte dan Hardy (2006), risiko perdarahan
pada setiap individu berbeda-beda. Tidak terdapat les laboratorium yang dapat menentukan
risiko perdarahan pada setiap individu, akan tetapi risiko perdarahan perioperasi meningkat
ketika digunakan 2 atau lebih kombinasi obat antiplatelet, seperti pada dual therapy aspirin dan
clopidogrel. Penghentian terapi antiplatelet secara tiba-tiba dan menyebabkan “rebound effect”
yang ditandai dengan inflamasi protrombotik, peningkatan adhesi dan agregasi platelet, serta
aktivitas tromboksan A2 yang berlebih. Pembedahan disertai peningkatan protrombotik dan
inflamasi yang disertai dengan drug-eluting stent endotelial yang tidak sempurna dapat
menyebabkan trombosis stent, infark myokardial, bahkan kematian (Newsome et al., 2008).
United States Food and Drug Administration merekomendasikan terapi dual antiplatelet
dilanjutkan minimal 3 bulan setelah pemasangan sirolimus-eluting stent dan minimal 6 bulan
setelah pemasangan pactitaxel-eluting stent. Meskipun demikian, setidaknya terapi diberikan
selama 1 tahun. Berikut ini adalah rekomendasi dari berbagai sumber mengenai penatalaksanaan
pasien dengan stent:
- Setelah pemasangan bare metal stent, prosedur ringan dan non-urgent harus ditunda
minimal 1 bulan, berdasarkan rekomendasi ACC/AHA joint advisory (Grines et al.,
2007) atau minimal 6 minggu, berdasarkan guideline ACC/AHA (Fleisher et al., 2007).
Data terbaru merekomendasikan optimal penundaan adalah 3 bulan (Nuttall et al.,
2008).
 - Pada pasien dengan jangka waktu pemasangan stent < 6 minggu yang membutuhkan
pembedahan segera, terapi dual antiplatelet harus dilanjutkan pada periode perioperasi
(Douketis et al., 2008).
- Setelah pemasangan drug-eluting stent, prosedur ringan dan non-urgent harus ditunda
minimal 12 bulan (Grines et al., 2007).
- Pada pasien dengan drug-eluting stent yang membutuhkan pembedahan yang tidak
boleh ditunda, terapi antiplatelet harus dilanjutkan tanpa dihentikan jika jangka waktu
pemasangan < 6 bulan. Jika sudah lebih dari 6 bulan sebelum urgent surgery maka
aspirin dilanjutkan tanpa dihentikan (≥ 81 mg/ hari) dan clopidogrel dilanjutkan sampai
5 hari sebelum pembedahan dan dilanjutkan segera setelah pembedahan (pada loading
dose 300 mg diikuti 75 mg/hari).

Penatalaksanaan Perdarahan Pascaoperasi

Terapi antiplatelet maupun antikoagulan yang dilanjutkan selama prosedur dental dapat
meningkatkan risiko perdarahan postoperasi, akan tetapi dengan menghentikan terapi tersebut
tidak menjamin tidak ada risiko perdarahan serius (Wahl, 2000). Menurut Scully dan Wolff
(2002), prosedur dental harus dilakukan pada pagi hari untuk mempersiapkan apabila terjadi
perdarahan secara tiba-tiba. Anestesi lokal yang mengandung vasokonstriktor diberikan dengan
teknik infiltrasi atau intraligamen. Blok nervus regional sebaiknya dihindari. Setelah prosedur
pencabutan perlu dilakukan dressing dengan absorbable dressing seperti oxycellulose (Surgicel),
collagen sponge (Haemocollagen) atau resorbable gelatin sponge (Spongostan) pada soket gigi
kemudian dilakukan suturing dengan benang absorbable. Seiring dengan dilakukan penutupan
soket, perlu juga dilakukan penekanan area bekas pencabutan dengan tampon yang digigit
selama 15-30 menit. Trauma yang ditimbulkan diusahakan seminimal mungkin.

Menurut Mandal dan Missouris (2005), pemberian obat antiperdarahan seperti asam
tranexamat dilaporkan oleh WHO menyebabkan deep vein thrombosis, pulmonary emboli,
cerebral emboli, dan arterial trombosis. Dalam penelitiannya Mandal dan Missouris
menyimpulkan bahwa pemberian asam tranexamat pada pasien dengan coronary artery disease
dapat mengendapkan trombosis arteri koroner dan memicu terjadinya infark miokardial.
 British Committee for Standards in Haematology merekomendasikan bahwa pasien yang
mengonsumsi warfarin tidak boleh diresepkan analgesik golongan NSAID nonselektif setelah
menjalani perawatan bedah mulut. Obat-obatan tersebut akan menghambat agregasi platelet dan
menyebabkan perdarahan gastrointestinal dan ulkus dan/ perforasi lambung (Dinkova et al.,
2013).

Dinkova A., Kirova D., Delev D., 2013, Management of Patients on Anticoagulant Therapy
Undergoing Dental Surgical Procedures, Review Article, Journal of IMAB, 19(4): 324.

Douketis J.D., Berger P.B., Dunn A.S., 2008, The perioperative management of antithrombotic
therapy: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines (8th Edition), Chest, 133(suppl 6):299S–339S.

Fleisher L.A., Beckman J.A., Brown K.A., 2007, ACC/AHA 2007 guidelines on perioperative
cardiovascular evaluation and care for noncardiac surgery: a report of the American
College of Cardiology/American Heart Association Task Force on Practice Guidelines
[published correction appears in J Am Coll Cardiol 2008; 52:794–797]. J Am Coll
Cardiol; 50:1707–1732.

Grines C.L., Bonow R.O., Casey D.E. Jr, 2007, Prevention of premature discontinuation of dual
antiplatelet therapy in patients with coronary artery stents: a science advisory from the
American Heart Association, American College of Cardiology, Society for
Cardiovascular Angiography and Interventions, American College of Surgeons, and
American Dental Association, with representation from the American College of
Physicians, Circulation, 115:813–818.

Hirsh J., Poller L., 1994, The International Normalized Ratio: A Guide to Understanding and
Correcting Its Problem, Arch Intern Med, 154, 282-288.

Jaffer A.K., 2009, Perioperative management of warfarin and antiplatelet therapy, Cleveland
Clinic Journal of Medicine, 76(4), S37-S44.
Kraai E.P., Lopes R.D., Alexander J.H., 2009, Perioperative management of anticoagulation:
guidelines translated for the clinician, J Thromb Thrombolysis, 28: 16-22.

Lecompte T., Hardy J.F., 2006, Antiplatelet agents and perioperative bleeding, Can J Anaesth,
53 (suppl 6), S103-S112.

Madan G.A., Madan S.G., Madan G., Madan A.D., 2005, Minor oral surgery without stopping
daily low-dose aspirin therapy: a study of 51 patients, J Oral Maxillofac Surg, 63, 1262-
1265.

Newsome L.T., Weller R.S., Gerancher J.C., Kutcher M.A., Royster R.L., 2008, Coronary artery
stents: II. Perioperative considerations and management, Anesth Analg, 107: 570-590.

Nuttall G.A., Brown M.J., Stombaugh J.W., 2008, Time and cardiac risk of surgery after bare
metal stent percutaneous coronary intervention, Anesthesiology, 109:588–595.

Pototski M., Amenabar J.M., 2007, Dental Management of Patients Reveiving Anticoagulation
or Antiplatelet Treatment, Journal of Oral Science, 49(4): 253-258.

Wahl M.J., 2000, Myths of Dental Surgery in Patients Receiving Aticoagulant Therapy, J Am
Dent Assoc, 131, 77-81.

MANAJEMEN PERIOPERATIF PADA PASIEN DENGAN TERAPI

ANTIKOAGULAN DAN ANTIPLATELET

A. Manajemen Perioperatif Pasien dengan Terapi Antikoagulan

American College of Chest Physicians (ACCP) merekomendasikan guideline untuk
manajemen antikoagulan pasien dalam kategori risiko berdasarkan indikasi dan lama pemakaian
termasuk adanya katup jantung buatan, riwayat fibrilasi atrium, atau riwayat tromboemboli vena
(VTE) (Jaffer, 2009).

Bridging anticoagulation (bridge therapy) merupakan pemberian sementara unfractioned

heparin secara intravena (IV UFH) atau low-molecular weight heparin (LMWH) sebelum
tindakan bedah. ACCP merekomendasikan pasien berdasarkan risiko terjadinya tromboemboli.

 Risiko tinggi – bridging antikoagulasi dengan LMWH subkutan atau IV UFH dengan
dosis terapetik
 Risiko sedang – bridging antikoagulasi dengan LMWH subkutan atau IV UFH dosis
terapetik, atau LMWH subkutan dosis rendah
 Risiko rendah – bridging antikoagulasi dengan LMWH subkutan dosis rendah atau
tanpa bridging
(Jaffer, 2009)

Sebelum dilakukan bridging therapy, perlu diidentifikasi apakah pasien membutuhkan

bridging therapy sebelum melakukan operasi/ bedah tertentu (Jaffer, 2009).
 (Jaffer, 2009)

Menurut Jaffer (2009), protokol terapi bridging antikoagulan adalah sebagai berikut.

Preoperasi

- Warfarin dihentikan 5 hari sebelum pembedahan (menghentikan 4 dosis) jika INR

preoperasi berkisar antara 2-3, atau 6 hari sebelum pembedahan (menghentikan 5 dosis)
jika INR preoperasi berkisar antara 3-4,5.
- Untuk bridge therapy, LMWH yang digunakan adalah enoxaparin 1 mg/kg BB atau
dalteparin 100 IU/kg BB melalui subkutan setiap 12 jam. LMWH mulai diberikan 36 jam
setelah diberikan dosis terakhir warfarin.
- Dosis terakhir LMWH diberikan sekitar 24 jam sebelum pembedahan
Pascaoperasi
- Untuk bedah minor, LMWH mulai diberikan kembali dengan dosis penuh sekitar 24 jam
pascaoperasi. Untuk bedah mayor dan untuk pasien dengan risiko perdarahan tinggi,
digunakan dosis profilaktik pada 2 hari pertama pascaoperasi.
- Warfarin diberikan kembali 1 hari pascaoperasi.
- INR dan prothrombin time diperiksa setiap hari sampai mencapai angka terapetik.
- LMWH dihentikan jika INR sudah berkisar antara 2-3 selama 2 hari berturut-turut.

(Kraai et al., 2009)

Secara umum, terapi warfarin dihentikan sebelum melakukan berbagai prosedur

pembedahan, termasuk bedah minor. Akan tetapi menurut Jaffer (2009), beberapa prosedur aman
dilakukan tanpa penghentian pemberian warfarin jangka panjang.

International normalized ratio (INR) merupakan nilai yang menunjukkan efektivitas

penggunaan terapi antikoagulan pada pasien secara akurat. INR dihitung dari perbandingan
antara prothrombin time (PT) pasien dengan PT kontrol yang dipangkatkan dengan International
sensitivity index value (ISI). Pasien dengan sistem koagulasi normal memiliki INR 1,0 (Hirsh
dan Poller, 1994). Idealnya INR diukur 24 jam sebelum dilakukan tindakan, akan tetapi pada
pasien yang memiliki INR stabil, pengukuran INR 72 jam sebelum prosedur masih dapat
diterima. Pada pasien dengan terapi antikoagulan, biasanya INR berkisar antara 2,0-4,0
tergantung alasan penggunaan antikoagulan (Dinkova et al., 2013). Nilai INR yang optimal
untuk prosedur bedah dental adalah 2,5 karena angka tersebut menunjukkan risiko minimal
terjadinya tromboemboli dan hemoragi. Akan tetapi prosedur bedah dental minor aman
dilakukan pada INR 2,0-4,0, disertai dengan kontrol perdarahan Pasien dengan INR lebih dari
4,0 sebaiknya tidak dilakukan tindakan bedah sampai dilakukan kontrol terapi antikoagulannya
(Pototski dan Amenabar, 2007).

Prosedur Dental dan Manajemen Antikoagulan

Menurut Madan (2005), prosedur bedah minor dental seperti pencabutan sederhana sampai
tiga gigi, bedah gingiva, prosedur mahkota-jaket, scaling supragingiva, dan pencabutan gigi
dengan pembedahan dapat dilakukan tanpa mengubah dosis medikasi baik antikoagulan maupun
antiplatelet. Jika akan dilakukan pencabutan lebih dari tiga gigi maka pencabutan dilakukan pada
beberapa kali kunjungan dan pada setiap kunjungan dilakukan pencabutan 2-3 gigi dalam satu
kuadran.

Bleeding risk Types of Procedures Recommendations

Low risk  Crown and bridge procedures  Do not interupt warfarin
 Multiple simple extractions therapy
 Periodontal exams, x-ray  Use local measures to
 Regional and local injections prevent or control bleeding
anesthetics  Consider other dental
 Restorations options if concerned: Limit
 Standard root canal 2-3 teeth (non-impacted,
 Sub-gingival scaling with inflamed bony or soft tissue)
gums estractions per dental
 Supra-gingival scaling, root planing, appointment
endodontics  Restrict scaling to one
 Surgical removal of teeth quadrant per visit and re-
assess
Moderate risk  Alveoloplasties  Same as above
 Apicoectomy (root removal)  Use extra caution
 Alveolar surgery (bone removal)
 Dental implants
 Full mouth extractions
High risk  Extensive surgery  Consider patient’s risk for
 Tori removal thromboembolic event. If
 Vestibuloplasty low, then may consider
 Free gingival graft adjusting warfarin dose
 Block bone graft  If risk of
thromboembolism is high,
then discuss with dentist
 and PCP. May consider
adjusting warfarin dose.

B. Manajemen Perioperatif Pasien dengan Terapi Antiplatelet

Pasien yang diberikan terapi antiplatelet adalah pasien dengan coronary stent yang apabila
terapi dihentikan dapat meningkatkan risiko terjadinya trombosis. Risiko trombosis pada pasien
dengan stent meningkat terutama pada periode pascaoperasi, terlebih jika pembedahan dilakukan
segera setelah pemasangan stent (Jaffer, 2009).
Manajemen perioperatif yang optimal pada pasien dengan stent arteri koroner bergantung
pada beberapa faktor, di antaranya tipe stent, lama implantasi stent, lokasi setiap stent pada
sirkulasi koroner, komplikasi revaskularisasi, riwayat trombosis stent, obat antiplatelet yang
digunakan, dan lain-lain (Jaffer, 2009). Menurut Lecompte dan Hardy (2006), risiko perdarahan
pada setiap individu berbeda-beda. Tidak terdapat les laboratorium yang dapat menentukan
risiko perdarahan pada setiap individu, akan tetapi risiko perdarahan perioperasi meningkat
ketika digunakan 2 atau lebih kombinasi obat antiplatelet, seperti pada dual therapy aspirin dan
clopidogrel. Penghentian terapi antiplatelet secara tiba-tiba dan menyebabkan “rebound effect”
yang ditandai dengan inflamasi protrombotik, peningkatan adhesi dan agregasi platelet, serta
aktivitas tromboksan A2 yang berlebih. Pembedahan disertai peningkatan protrombotik dan
inflamasi yang disertai dengan drug-eluting stent endotelial yang tidak sempurna dapat
menyebabkan trombosis stent, infark myokardial, bahkan kematian (Newsome et al., 2008).
United States Food and Drug Administration merekomendasikan terapi dual antiplatelet
dilanjutkan minimal 3 bulan setelah pemasangan sirolimus-eluting stent dan minimal 6 bulan
setelah pemasangan pactitaxel-eluting stent. Meskipun demikian, setidaknya terapi diberikan
selama 1 tahun. Berikut ini adalah rekomendasi dari berbagai sumber mengenai penatalaksanaan
pasien dengan stent:
- Setelah pemasangan bare metal stent, prosedur ringan dan non-urgent harus ditunda
minimal 1 bulan, berdasarkan rekomendasi ACC/AHA joint advisory (Grines et al.,
2007) atau minimal 6 minggu, berdasarkan guideline ACC/AHA (Fleisher et al., 2007).
Data terbaru merekomendasikan optimal penundaan adalah 3 bulan (Nuttall et al.,
2008).
 - Pada pasien dengan jangka waktu pemasangan stent < 6 minggu yang membutuhkan
pembedahan segera, terapi dual antiplatelet harus dilanjutkan pada periode perioperasi
(Douketis et al., 2008).
- Setelah pemasangan drug-eluting stent, prosedur ringan dan non-urgent harus ditunda
minimal 12 bulan (Grines et al., 2007).
- Pada pasien dengan drug-eluting stent yang membutuhkan pembedahan yang tidak
boleh ditunda, terapi antiplatelet harus dilanjutkan tanpa dihentikan jika jangka waktu
pemasangan < 6 bulan. Jika sudah lebih dari 6 bulan sebelum urgent surgery maka
aspirin dilanjutkan tanpa dihentikan (≥ 81 mg/ hari) dan clopidogrel dilanjutkan sampai
5 hari sebelum pembedahan dan dilanjutkan segera setelah pembedahan (pada loading
dose 300 mg diikuti 75 mg/hari).

Penatalaksanaan Perdarahan Pascaoperasi

Terapi antiplatelet maupun antikoagulan yang dilanjutkan selama prosedur dental dapat
meningkatkan risiko perdarahan postoperasi, akan tetapi dengan menghentikan terapi tersebut
tidak menjamin tidak ada risiko perdarahan serius (Wahl, 2000). Menurut Scully dan Wolff
(2002), prosedur dental harus dilakukan pada pagi hari untuk mempersiapkan apabila terjadi
perdarahan secara tiba-tiba. Anestesi lokal yang mengandung vasokonstriktor diberikan dengan
teknik infiltrasi atau intraligamen. Blok nervus regional sebaiknya dihindari. Setelah prosedur
pencabutan perlu dilakukan dressing dengan absorbable dressing seperti oxycellulose (Surgicel),
collagen sponge (Haemocollagen) atau resorbable gelatin sponge (Spongostan) pada soket gigi
kemudian dilakukan suturing dengan benang absorbable. Seiring dengan dilakukan penutupan
soket, perlu juga dilakukan penekanan area bekas pencabutan dengan tampon yang digigit
selama 15-30 menit. Trauma yang ditimbulkan diusahakan seminimal mungkin.

Menurut Mandal dan Missouris (2005), pemberian obat antiperdarahan seperti asam
tranexamat dilaporkan oleh WHO menyebabkan deep vein thrombosis, pulmonary emboli,
cerebral emboli, dan arterial trombosis. Dalam penelitiannya Mandal dan Missouris
menyimpulkan bahwa pemberian asam tranexamat pada pasien dengan coronary artery disease
dapat mengendapkan trombosis arteri koroner dan memicu terjadinya infark miokardial.
 British Committee for Standards in Haematology merekomendasikan bahwa pasien yang
mengonsumsi warfarin tidak boleh diresepkan analgesik golongan NSAID nonselektif setelah
menjalani perawatan bedah mulut. Obat-obatan tersebut akan menghambat agregasi platelet dan
menyebabkan perdarahan gastrointestinal dan ulkus dan/ perforasi lambung (Dinkova et al.,
2013).

Dinkova A., Kirova D., Delev D., 2013, Management of Patients on Anticoagulant Therapy
Undergoing Dental Surgical Procedures, Review Article, Journal of IMAB, 19(4): 324.

Douketis J.D., Berger P.B., Dunn A.S., 2008, The perioperative management of antithrombotic
therapy: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines (8th Edition), Chest, 133(suppl 6):299S–339S.

Fleisher L.A., Beckman J.A., Brown K.A., 2007, ACC/AHA 2007 guidelines on perioperative
cardiovascular evaluation and care for noncardiac surgery: a report of the American
College of Cardiology/American Heart Association Task Force on Practice Guidelines
[published correction appears in J Am Coll Cardiol 2008; 52:794–797]. J Am Coll
Cardiol; 50:1707–1732.

Grines C.L., Bonow R.O., Casey D.E. Jr, 2007, Prevention of premature discontinuation of dual
antiplatelet therapy in patients with coronary artery stents: a science advisory from the
American Heart Association, American College of Cardiology, Society for
Cardiovascular Angiography and Interventions, American College of Surgeons, and
American Dental Association, with representation from the American College of
Physicians, Circulation, 115:813–818.

Hirsh J., Poller L., 1994, The International Normalized Ratio: A Guide to Understanding and
Correcting Its Problem, Arch Intern Med, 154, 282-288.

Jaffer A.K., 2009, Perioperative management of warfarin and antiplatelet therapy, Cleveland
Clinic Journal of Medicine, 76(4), S37-S44.
Kraai E.P., Lopes R.D., Alexander J.H., 2009, Perioperative management of anticoagulation:
guidelines translated for the clinician, J Thromb Thrombolysis, 28: 16-22.

Lecompte T., Hardy J.F., 2006, Antiplatelet agents and perioperative bleeding, Can J Anaesth,
53 (suppl 6), S103-S112.

Madan G.A., Madan S.G., Madan G., Madan A.D., 2005, Minor oral surgery without stopping
daily low-dose aspirin therapy: a study of 51 patients, J Oral Maxillofac Surg, 63, 1262-
1265.

Newsome L.T., Weller R.S., Gerancher J.C., Kutcher M.A., Royster R.L., 2008, Coronary artery
stents: II. Perioperative considerations and management, Anesth Analg, 107: 570-590.

Nuttall G.A., Brown M.J., Stombaugh J.W., 2008, Time and cardiac risk of surgery after bare
metal stent percutaneous coronary intervention, Anesthesiology, 109:588–595.

Pototski M., Amenabar J.M., 2007, Dental Management of Patients Reveiving Anticoagulation
or Antiplatelet Treatment, Journal of Oral Science, 49(4): 253-258.

Wahl M.J., 2000, Myths of Dental Surgery in Patients Receiving Aticoagulant Therapy, J Am
Dent Assoc, 131, 77-81.
Perioperative management of patients receiving anticoagulants
Authors:
James D Douketis, MD, FRCPC, FACP, FCCP
Gregory YH Lip, MD, FRCPE, FESC, FACC
Section Editor:
Lawrence LK Leung, MD
Deputy Editor:
Jennifer S Tirnauer, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Mar 2022. | This topic last updated: Mar 11, 2022.
Please read the Disclaimer at the end of this page.

INTRODUCTION The management of anticoagulation in patients undergoing surgical

procedures is challenging, since interrupting anticoagulation for a procedure transiently increases

the risk of thromboembolism. At the same time, surgery and invasive procedures have associated
bleeding risks that are increased by the anticoagulant(s) administered for thromboembolism
prevention. If the patient bleeds from the procedure, their anticoagulant may need to be
discontinued for a longer period, resulting in a longer period of increased thromboembolic risk.
A balance between reducing the risk of thromboembolism and preventing excessive bleeding
must be reached for each patient.
Other clinical issues are anticoagulant specific. For those taking a vitamin K antagonist, it takes
several days until the anticoagulant effect is reduced and then re-established perioperatively; the
risks and benefits of "bridging" with a shorter acting agent, such as heparin, during this time are
unclear. The direct oral anticoagulants (DOACs; dabigatran, factor Xa inhibitors
[rivaroxaban, apixaban, edoxaban]) have shorter half-lives, making them easier to discontinue
and resume rapidly.

Our approach to managing ongoing anticoagulation in patients undergoing surgery or an invasive

procedure is discussed here. Additional details regarding the use of specific anticoagulants and
antiplatelet agents are presented separately.

●Vitamin K antagonists – (See "Warfarin and other VKAs: Dosing and adverse effects".)
●Heparins – (See "Heparin and LMW heparin: Dosing and adverse effects".)
●Direct thrombin inhibitors and direct factor Xa inhibitors – (See "Direct oral
anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse
effects".)
●Antiplatelet agents – (See "Perioperative medication management", section on
'Medications affecting hemostasis'.)
Specific recommendations for individuals with prosthetic heart valves are discussed separately.
(See "Antithrombotic therapy for prosthetic heart valves: Management of bleeding and invasive
procedures".)
Perioperative venous thromboembolism prevention in patients not receiving ongoing
anticoagulation is also discussed separately. (See "Prevention of venous thromboembolic disease
in adult nonorthopedic surgical patients" and "Prevention of venous thromboembolism in adult
orthopedic surgical patients".)

OVERVIEW OF OUR APPROACH

General approach — Interruption of anticoagulation temporarily increases thromboembolic

risk, and continuing anticoagulation increases the risk of bleeding associated with invasive
procedures; both of these outcomes can increase mortality rates [1-6]. Our approach to
perioperative management of anticoagulation takes into account and balances these risks, along
with specific features of the anticoagulant the patient is taking [7].

Much of our approach is based on expert opinion; thrombotic and bleeding risks may vary
depending on individual circumstances, and data from randomized trials or well-designed
observational studies are not available to guide practice in many settings. In addition, the best
surrogate for complete resolution of anticoagulant effect is not always known or available for the
newer direct oral anticoagulants (DOACs). Thus, this approach should be used as clinical
guidance and should not substitute for clinician judgment in decisions about perioperative
anticoagulant management for individual patients.

Our approach to decision-making is outlined as follows; this is presented in an interactive format

on the Thrombosis Canada website:
 ●Estimate thromboembolic risk – The higher the thromboembolic risk, the greater the
importance of minimizing the interval without anticoagulation (table 1). We estimate
thromboembolic risk for patients with atrial fibrillation based on age and comorbidities.
For those with a recent deep vein thrombosis (DVT) or pulmonary embolism (PE), we
estimate the risk based on the interval since diagnosis.
If thromboembolic risk is transiently increased (eg, recent stroke, recent PE), we prefer to
delay surgery until the risk returns to baseline, if possible. (See 'Estimating
thromboembolic risk' below.)
For patients with more than one condition that predisposes to thromboembolism, the
condition with the highest thromboembolic risk takes precedence.
●Estimate bleeding risk – A higher bleeding risk confers a greater need for perioperative
hemostasis and hence a longer period of anticoagulant interruption. Bleeding risk is
dominated by the type and urgency of surgery; some patient comorbidities also contribute.
Procedures with a low bleeding risk (eg, dental extractions, minor skin surgery) often can
be performed without interruption of anticoagulation. (See 'Estimating procedural bleeding
risk' below and 'Deciding whether to interrupt anticoagulation' below.)
●Determine the timing of anticoagulant interruption – The timing of anticoagulant
interruption depends on the specific agent the patient is receiving. Warfarin requires earlier
discontinuation than the DOACs (dabigatran, rivaroxaban, apixaban, edoxaban).
Additional considerations may be required in individuals with reduced kidney and/or liver
function. (See 'Timing of anticoagulant interruption' below.)
●Determine whether to use bridging anticoagulation – For most patients, we do not use
bridging anticoagulation (use of a short-acting parenteral agent to reduce the interval
without anticoagulation), because it increases bleeding risk without reducing the rate of
thromboembolism. However, some patients on warfarin with an especially high
thromboembolic risk (eg, mechanical heart valve, recent stroke) may benefit from
bridging. (See 'Bridging anticoagulation' below.)
Example cases — The following examples illustrate our decision-making process using this
approach in general terms; management of every case must be individualized based on the
judgment of the treating clinicians:
●A 76-year-old female with nonvalvular atrial fibrillation, hypertension, and prior stroke
three months ago, receiving warfarin, requires elective hip replacement with neuraxial
anesthesia; kidney function is normal, and weight is 75 kg. This patient has a very high
thromboembolic risk (table 1) and a high bleeding risk (table 2).
•Omit warfarin for five days before the procedure (last dose on preoperative day minus
6).
•Preoperative bridging with therapeutic-dose low molecular weight (LMW) heparin
(eg, dalteparin, 100 units/kg [7500 units] subcutaneously twice daily) starting on
preoperative day minus 3, with last dose on the morning of day minus 1.
•Resume warfarin within 24 hours after surgery (usual dose).
•Postoperative low-dose LMW heparin for venous thromboembolism (VTE)
prevention (eg, dalteparin, 5000 units subcutaneously once daily) within 24 hours after
surgery until postoperative bridging is started.
•Postoperative bridging on postoperative day 2 or 3, when hemostasis is secured
(eg, dalteparin, 100 units/kg [7500 units] subcutaneously twice daily); continue for at
least four to five days, until the international normalized ratio (INR) is therapeutic.
 ●A 70-year-old male with nonvalvular atrial fibrillation, diabetes, and hypertension
(CHA2DS2-VASc score = 3) receiving dabigatran who requires a colon resection for
cancer; kidney function is normal. This patient has a moderate thrombotic risk (table 1)
and a high bleeding risk (table 2).
•Omit dabigatran for two days before the procedure (last dose of dabigatran on day
minus 3).
•No bridging.
•Resume dabigatran on postoperative day 2 or 3, when patient is able to take
medication by mouth.
•Use prophylactic-dose LMW heparin for VTE prophylaxis for the first two to three
postoperative days.
●A 55-year-old male with an unprovoked DVT four months ago, receiving apixaban 5 mg
twice daily, who requires a colonoscopy because of a personal history of premalignant
colorectal polyps; kidney function is normal. This patient has a high thrombotic risk (table
1) and a low bleeding risk (table 2).
•Omit apixaban for one day before the procedure (last dose of apixaban on day minus
2).
•No bridging.
•Resume apixaban the day after the procedure, after at least 24 hours have elapsed and
when hemostasis is secured. If the patient requires polyp removal, delay resumption of
apixaban for one to two more days.
●A 68-year-old female with nonvalvular atrial fibrillation, hypertension, and congestive
heart failure (CHA2DS2-VASc score = 4), receiving rivaroxaban 15 mg daily in the
morning, requires a dental cleaning and two dental extractions; creatinine clearance (CrCl)
is 35 mL/min. This patient has a moderate thrombotic risk (table 1) and a low bleeding risk
(table 2).
•Omit rivaroxaban on the day of the procedure.
•Use oral tranexamic acid mouthwash just before the procedure and two to three times
that day after the procedure.
•Resume rivaroxaban the day after the procedure, after at least 24 hours have elapsed
(assuming the dental extractions were uneventful).

ESTIMATING THROMBOEMBOLIC RISK The major factors that increase

thromboembolic risk are atrial fibrillation, prosthetic heart valves, and recent venous or arterial
thromboembolism (eg, within the preceding three months).
Atrial fibrillation — Atrial fibrillation accounts for the highest percentage of patients for whom
perioperative anticoagulation questions arise. Patients with atrial fibrillation are a heterogeneous
group; risk can be further classified according to clinical variables such as age, hypertension,
congestive heart failure, diabetes, prior stroke, and other vascular disease (table 1) [2,8]. The
CHA2DS2-VASc score (table 3) (calculator 1), which incorporates these variables, is discussed in
detail separately, but use of risk scores has not been prospectively validated in the perioperative
setting.
The magnitude of this issue was illustrated in three large trials: RE-LY (Randomized Evaluation
of Long-Term Anticoagulant Therapy), ROCKET AF (Rivaroxaban Once daily, oral direct
factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke
and Embolism Trial in Atrial Fibrillation), and ARISTOTLE (Apixaban for Reduction in Stroke
and Other Thromboembolic Events in Atrial Fibrillation) [9-11]. In these trials, a total of 15,000
to 20,000 patients were randomly assigned to warfarin versus one of the direct oral
anticoagulants (dabigatran, rivaroxaban, or apixaban, respectively). Surgical or other invasive
procedures were required in one-fourth of patients in RE-LY and one-third of patients in
ROCKET AF and ARISTOTLE.
●RE-LY (dabigatran versus warfarin) – Of the 4591 patients who underwent elective
procedures in RE-LY, the perioperative thromboembolic risk was 1.2 percent, based on a
composite endpoint of stroke, cardiovascular death, and pulmonary embolus (PE) [9].
There were no differences in thromboembolic risk with dabigatran versus warfarin, or with
the high versus the low dabigatran dose. However, urgent surgery was associated with a
higher risk of ischemic stroke or systemic embolism than elective surgery (warfarin: 1.8
versus 0.4 percent; dabigatran 150 mg twice daily: 1.4 versus 0.4 percent; dabigatran 110
mg twice daily: 2.8 versus 0.3 percent).
●ROCKET AF (rivaroxaban versus warfarin) – Of the 4692 anticoagulant interruptions in
this trial, 40 percent were for surgery or invasive procedures [11]. The thromboembolic
risk during anticoagulant interruption was similar for rivaroxaban and warfarin (0.3 and
0.4 percent).
●ARISTOTLE (apixaban versus warfarin) – During 9260 procedures performed on
patients in the ARISTOTLE trial, the perioperative thromboembolic risk was 0.57 percent
for warfarin and 0.35 percent for apixaban [10].
Bleeding risk in these trials and registries are presented below. (See 'Overview of whether to
interrupt' below.)
Prosthetic heart valve — The risks of thromboembolism and perioperative management of
patients with prosthetic heart valves are discussed separately. (See "Antithrombotic therapy for
prosthetic heart valves: Management of bleeding and invasive procedures", section on
'Management of antithrombotic therapy for invasive procedures' and "Diagnosis of mechanical
prosthetic valve thrombosis or obstruction".)
Recent thromboembolism — Thromboembolic risk is greater in the immediate period
following a thromboembolic event and declines over time. Individuals with a recent
thromboembolic event (eg, within the previous three months) are likely to benefit from delaying
surgery, if possible. There are no high-quality data to determine when risk declines to baseline. If
emergency surgery is required (eg, acute cholecystectomy), bridging anticoagulation may be
used to reduce the interval without an anticoagulant. (See 'Bridging anticoagulation' below.)
Venous — The perioperative risk of venous thromboembolism (VTE) is greatest in individuals
with an event (eg, deep vein thrombosis [DVT], PE) within the prior three months and those with
a history of VTE associated with a high-risk inherited thrombophilia (table 1). However, many
patients with VTE do not require thrombophilia testing, and we do not perform this testing
specifically to evaluate perioperative thrombotic risk in patients who otherwise do not warrant
screening. Appropriate use of thrombophilia screening is discussed separately. (See "Clinical
presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the
lower extremity".)

Individuals with cancer have a moderate risk, and those with a thromboembolic event more than
one year ago have a low risk of VTE complications.
Thus, patients who require surgery within the first three months following an episode of VTE are
likely to benefit from delaying elective surgery, even if the delay is only for a few weeks. This
approach is supported by data showing that the recurrence risk for individuals with a recent VTE
is highest within the initial three to four weeks and diminishes over the following two months
[12-14]. Without anticoagulation, the early risk of recurrent VTE was approximately 50 percent;
treatment with warfarin for one month reduced this risk to 8 to 10 percent, and after three months
of warfarin therapy the risk declined to 4 to 5 percent [14-16].
Arterial — The risk of recurrent arterial embolism from any cardiac source is approximately 0.5
percent per day in the first month after an acute event [17]. Thus, patients with a recent arterial
embolism are likely to benefit from delaying elective surgery, if such a delay is possible.
The vast majority of cases are due to atrial fibrillation; other less common cardiac sources
include paradoxical embolism, nonbacterial thrombotic endocarditis in a patient with
malignancy, dilated or poorly contractile left ventricle, or left ventricular aneurysm [18-20].

ESTIMATING PROCEDURAL BLEEDING RISK The risk of bleeding is dominated

by the type of surgery or procedure. Comorbidities (eg, older age, reduced kidney function) and
medications that affect hemostasis (eg, aspirin) may also contribute [3,21,22].
As a general guideline, we divide procedures into high and low bleeding risk (two-day risk of
major bleeding 2 to 4 percent or 0 to 2 percent, respectively); examples of high bleeding risk
procedures include coronary artery bypass surgery, kidney biopsy, and any procedure lasting >45
minutes; low bleeding risk procedures include cholecystectomy, carpal tunnel repair, and
abdominal hysterectomy (table 2) [2]. These categories do not substitute for clinical judgment or
consultation between the surgeon and other treating clinicians. Neuraxial, intracranial, and
cardiac procedures are especially concerning because the location of potential bleeding increases
the risk of serious complications. (See "Neuraxial anesthesia/analgesia techniques in the patient
receiving anticoagulant or antiplatelet medication".)
Major bleeding is generally defined as bleeding that is fatal, involves a critical anatomic site (eg,
intracranial, pericardial), requires surgery to correct, lowers the hemoglobin by ≥2 g/dL, or
requires transfusion of ≥2 units packed red cells; however, there is heterogeneity in definitions
used by different clinicians [23].

The risks of some specific types of procedures are also discussed in detail separately in the
following topic reviews, along with management issues specific to those procedures:

●Neuraxial anesthesia – (See "Neuraxial anesthesia/analgesia techniques in the patient

receiving anticoagulant or antiplatelet medication".)
●Gastrointestinal procedures – (See "Management of anticoagulants in patients
undergoing endoscopic procedures", section on 'Elective procedures'.)
●Percutaneous coronary intervention (eg, angioplasty, atherectomy, stenting) –
(See "Periprocedural management of antithrombotic therapy in patients receiving long-
term oral anticoagulation and undergoing percutaneous coronary intervention", section on
'Elective patients' and "Coronary artery disease patients requiring combined anticoagulant
and antiplatelet therapy", section on 'Prevention'.)
●Ophthalmologic procedures – (See "Diabetic retinopathy: Prevention and treatment",
section on 'Patients taking antiplatelet or anticoagulant medication' and "Age-related
 macular degeneration: Treatment and prevention", section on 'Safety in patients taking
anticoagulants or antiplatelet drugs' and "Cataract in adults", section on 'Management of
antithrombotic agents'.)
Dental and cutaneous procedures are generally associated with a low risk of bleeding.
(See 'Settings in which continuing the anticoagulant may be preferable' below.)
Patient factors can also contribute to bleeding risk; these patient-related risks can be quantified
using bleeding risk scores. An example is the HAS-BLED score (calculator 2), which was used
in the BNK Online Bridging Registry (BORDER), an observational registry that assessed
perioperative outcomes in outpatients undergoing invasive cardiac procedures (cardiac
catheterization, pacemaker implantation, cardiac surgery) [24]. The HAS-BLED score assigns
one point each for hypertension, abnormal kidney or liver function (two points for
both), stroke, bleeding tendency, labile INRs, elderly age, and antiplatelet drugs or alcohol (table
4).
Nearly all of the patients in the BORDER study were receiving a vitamin K antagonist, which
was interrupted for the procedure and replaced with a bridging agent, usually a low molecular
weight (LMW) heparin. There were 35 clinically relevant bleeding episodes during 1000
procedures (3.5 percent). A HAS-BLED bleeding risk score ≥3 was the most predictive variable
for bleeding (hazard ration [HR] 11.8, 95% CI 5.6-24.9) [24].

DECIDING WHETHER TO INTERRUPT ANTICOAGULATION

Overview of whether to interrupt — Once the thromboembolic and bleeding risks have been
estimated, a decision can be made about whether the anticoagulant should be interrupted or
continued. Data comparing the relative benefits of continuing anticoagulation versus interrupting
an anticoagulant are limited, and decisions that balance thromboembolic and bleeding risks must
be made on a case-by-case basis. No scoring system can substitute for clinical judgment in this
decision making.
Our approach is illustrated in the algorithm (algorithm 1) and summarized as follows:
●In general, the anticoagulant must be discontinued if the surgical bleeding risk is high.
Those at very high or high thromboembolic risk should limit the period without
anticoagulation to the shortest possible interval; in some cases, this involves the use of a
bridging agent. (See 'Settings requiring anticoagulant interruption' below.)
●In contrast, individuals undergoing selected low bleeding risk surgery often can continue
their anticoagulant; in certain cases, continuation of the anticoagulant may be preferable.
(See 'Settings in which continuing the anticoagulant may be preferable' below.)

Practices to reduce bleeding and thromboembolic risks should be employed regardless of

whether the patient's anticoagulant is interrupted or continued. Examples include the following:

●Agents that interfere with platelet function (nonsteroidal antiinflammatory drugs

[NSAIDs], aspirin) should be avoided for routine analgesia unless the benefit outweighs
the increased risk of bleeding; routine perioperative use of aspirin should be avoided due
to an increased risk of bleeding and lack of benefit. By contrast, if these agents are
administered for a separate indication (eg, recent stroke, acute coronary syndromes,
implanted coronary stent), they can (and generally should) be continued [25].
Perioperative aspirin use is discussed in detail separately. (See "Perioperative medication
 management", section on 'Medications affecting hemostasis' and "Periprocedural
management of antithrombotic therapy in patients receiving long-term oral anticoagulation
and undergoing percutaneous coronary intervention".)
●For those not receiving an anticoagulant in the immediate postoperative period,
thromboprophylaxis to reduce the risk of venous thromboembolism (VTE) should be used
when appropriate. (See "Prevention of venous thromboembolic disease in adult
nonorthopedic surgical patients".)
Settings requiring anticoagulant interruption — Individuals undergoing surgery with a high
risk of bleeding will require interruption of their usual anticoagulant perioperatively, putting
them at higher risk of thromboembolic complications related to their underlying condition.
●If the very high risk of thromboembolism is transient (eg, ischemic stroke within the
previous three months), attempts should be made to delay elective surgery, if possible,
until the thromboembolic risk has returned to baseline.
It may also be advisable to delay elective surgery in a patient with atrial fibrillation who
has had inadequate anticoagulation in the preceding month. This is based on the
observation that among patients with nonvalvular atrial fibrillation, over 85 percent of
thrombi resolve after four weeks of warfarin therapy [26].
●Individuals with a temporarily very high or high thromboembolic risk in whom surgery
cannot be delayed (eg, potentially curative cancer surgery in a patient who just had an
acute VTE) should limit the interval without an anticoagulant to minimize the risk of VTE
recurrence. This generally involves stopping the usual anticoagulant as close to surgery as
possible, restarting it as soon as possible, and, for those on warfarin, using a bridging agent
before and/or after surgery while the usual anticoagulant is not therapeutic. A temporary
inferior vena cava (IVC) filter may also be appropriate in selected individuals.
(See 'Timing of anticoagulant interruption' below and 'Bridging anticoagulation' below
and 'Temporary IVC filters' below.)
●For individuals with a chronically elevated thromboembolic risk who are
receiving warfarin, we often use bridging anticoagulation to minimize the period when
anticoagulation is not being used. (See 'Limited indications for bridging' below.)
●Individuals with a moderate thromboembolic risk generally can interrupt their
anticoagulant for surgery without bridging. The bleeding risk from bridging may outweigh
any potential benefit, especially in those with low-risk nonvalvular atrial fibrillation
[27,28].
Temporary IVC filters — Placement of a temporary inferior vena cava (IVC) filter is indicated
in patients with a very recent (within the prior three to four weeks) acute VTE who require
interruption of anticoagulation for a surgery or major procedure in which it is anticipated that
therapeutic-dose anticoagulation will need to be delayed for more than 12 hours postoperatively.
As an example, most patients who require surgery using general or neuraxial anesthesia that
must be performed within three to four weeks of an acute VTE would require placement of an
IVC filter. Further information about the placement of IVC filters is presented separately.
(See "Placement of vena cava filters and their complications".)

In contrast, patients who require temporary interruption of anticoagulation for a minor procedure
such as central venous catheter placement, which may be performed with omission of one dose
of an anticoagulant, would not require an IVC filter. Individuals with a VTE more than four
weeks prior to the intended surgery do not require placement of an IVC filter, and other clinical
situations such as prior perioperative VTE or high-risk thrombophilia are not routine indications
for perioperative placement of an IVC filter.

Settings in which continuing the anticoagulant may be preferable — For individuals

undergoing selected surgery that confers a low risk of bleeding (eg, cataract extraction) it may be
preferable for them to continue their anticoagulant, depending on patient factors and the
judgment of the treating clinician. Continuing the anticoagulant likely reduces the risk of
thromboembolism, and in some settings (eg, cardiac implantable electronic device) it actually
reduces the risk of bleeding as well. For those receiving warfarin or another vitamin K
antagonist, it is important to confirm that the international normalized ratio (INR) is not above
the therapeutic range at the time of the procedure.
●Dental procedures – Dental procedures are generally considered to confer a low risk of
bleeding, and anticoagulation can be continued in most patients during these procedures.
The evidence for the safety of continuing anticoagulation comes from patients
receiving warfarin with an INR in the therapeutic range [29-35]. In the ARISTOTLE trial,
which included patients anticoagulated with warfarin versus apixaban for atrial fibrillation,
perioperative bleeding rates were approximately 1 percent in patients undergoing dental
and other low bleeding risk procedures. Bleeding can be further reduced with the use of
topical hemostatic agents (eg, tranexamic acid mouthwash, used three to four times daily
for one to two days) [8,34,36-39].
An exception is multiple tooth extractions, which we consider high bleeding risk.
(See 'Settings requiring anticoagulant interruption' above.)
●Cutaneous procedures – Cutaneous procedures (eg, skin biopsy, tumor excision) are
also generally considered to confer a low risk of bleeding; the potential for local control
measures further reduces concerns about bleeding risk.
●Selected cardiac procedures – For certain cardiac procedures, there is evidence that
continuing anticoagulation is safe (and in some cases associated with better outcomes)
compared with stopping and restarting the anticoagulant.
•Cardiac implantable devices – We agree with a position document from the
European Heart Rhythm Association (EHRA) that states the majority of patients
undergoing implantation of a cardiac electronic device (pacemaker, cardioverter-
defibrillator) should continue their anticoagulant perioperatively [40]. This is based on
data from the BRUISE CONTROL trial, which randomly assigned patients
on warfarin undergoing implantation of a cardiac implantable electronic device to
continuation of warfarin or heparin bridging, as well as other smaller trials [41]. This
trial found a lower risk of bleeding in patients who continued warfarin. Potential
explanations for the increased bleeding in the heparin-bridging arm include initiation
of post-procedure bridging too early (eg, within 24 hours after the procedure) or better
identification of surgical bleeding sites that could be addressed during the procedure in
patients receiving continued warfarin.
An exception is a patient with a low risk of thromboembolic events, in
whom warfarin may be discontinued, or a patient receiving a direct oral anticoagulant
(DOAC), for whom temporary discontinuation is likely to be appropriate; bridging
anticoagulation is not recommended in such individuals [40]. In an analysis of 611
patients from the RE-LY trial (dabigatran versus warfarin in atrial fibrillation) who
underwent implantable device surgery, pocket hematomas occurred at a similar
frequency in those who had interruption of dabigatran and those who had interruption
 of warfarin without bridging [42]. It is not clear whether uninterrupted dabigatran
would be associated with lower risks of bleeding and/or thrombosis. (See "Cardiac
implantable electronic devices: Periprocedural complications".)
•Endovascular procedures and catheter ablation – Endovascular procedures include
a variety of venous and arterial interventions, such as angioplasty, catheter ablation,
and atherectomy. In a meta-analysis of randomized trials involving over 20,000
patients undergoing these procedures, uninterrupted warfarin therapy was associated
with equivalent or lower rates of complications compared with interruption of warfarin
[43]. As an example, a benefit of warfarin continuation rather than discontinuation
with bridging was reported in the COMPARE trial, which randomly assigned patients
with atrial fibrillation undergoing catheter ablation to continued warfarin or
discontinuation of warfarin with bridging [44]. In this trial, patients randomized to
continue warfarin had a lower risk of stroke and less bleeding.
We also agree with the EHRA position document statement that all patients
undergoing catheter ablation for atrial fibrillation should receive full anticoagulation
with heparin in addition to continuing their oral anticoagulant [40].
If a decision is made to discontinue the anticoagulant (eg, patient with impaired kidney function),
bridging is reserved for those with a high to very high thromboembolic risk and not used for
those with a moderate thromboembolic risk. (See 'Limited indications for bridging' below.)

TIMING OF ANTICOAGULANT INTERRUPTION If a decision has been made to

interrupt the anticoagulant for surgery with high or moderate bleeding risk, the agent should be
stopped in sufficient time to allow anticoagulation to resolve. For some agents such as warfarin,
laboratory testing is a reliable indicator that the anticoagulant effect has resolved after
discontinuation; for direct oral anticoagulants (DOACs), well-validated and easily accessible
testing is not always available. Data to guide the timing of anticoagulant interruption are
evolving, especially for DOACs, and much of our practice is based on expert opinion and
observational studies as we await results from ongoing trials [45].
●Validated approaches have been developed to guide the timing of DOAC interruption.
(See 'DOAC interruptions (overview)' below.)
●If a moderate or high bleeding risk surgery is required urgently or immediately, reversal
of the anticoagulant may also be required. (See 'Urgent/emergency invasive
procedure' below.)
●Risks of bleeding with neuraxial anesthesia and risks of thrombosis in patients with
prosthetic heart valves are especially concerning; these issues are discussed in detail
separately. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving
anticoagulant or antiplatelet medication" and "Antithrombotic therapy for mechanical heart
valves".)
Typical durations of anticoagulant interruption are illustrated by the RE-LY trial, which
randomly assigned individuals with nonvalvular atrial fibrillation to warfarin or dabigatran for
prevention of thromboembolism [9]. In this trial, nearly half of patients treated with dabigatran
had surgery within 48 hours of stopping the drug, whereas only approximately 1 in 10 patients
treated with warfarin had surgery within 48 hours of drug discontinuation. The incidence of
thromboembolism was low (<1 percent), and bleeding rates were similar for those receiving
warfarin or either dabigatran dose. Similar findings were reported in the PAUSE study, which
focused on individuals with atrial fibrillation receiving a DOAC. (See 'Atrial fibrillation' above
and 'DOAC interruptions (overview)' below.)
Warfarin interruption — Warfarin blocks a vitamin K-dependent step in clotting factor
production; it impairs coagulation by interfering with the functions of factors II (prothrombin),
VII, IX, and X. Resolution of warfarin effect is determined by measurement of the prothrombin
time (PT), which is standardized across institutions using an international normalized ratio
(INR).
●Discontinuation – If warfarin discontinuation is appropriate, we typically omit warfarin
for five days before elective surgery (ie, the last dose of warfarin is given on day minus 6)
and, when possible, check the PT/INR on the day before surgery [8,14,46,47]. If the INR
is >1.5, we administer a low dose of oral vitamin K (eg, 1 to 2 mg) to hasten normalization
of the PT/INR and recheck the INR the following day. We proceed with surgery when the
INR is ≤1.4. An INR in the normal range is especially important in patients undergoing
surgery associated with a high bleeding risk (eg, intracranial, spinal, urologic) or if
neuraxial anesthesia is to be used. (See 'Estimating procedural bleeding risk' above
and 'Neuraxial anesthesia' below.)
This timing of warfarin discontinuation is based on the biologic half-life of warfarin (36 to
42 hours) and the observed time for the PT/INR to return to normal after stopping warfarin
(two to three days for the INR to fall to below 2; four to six days to normalize) [46].
Normalization of the INR may take longer in patients receiving higher-intensity
anticoagulation (INR 2.5 to 3.5) and in older individuals [48]. Half-lives of other vitamin
K antagonists also differ (eg, 8 to 11 hours for acenocoumarol; approximately four to six
days for phenprocoumon [49]; approximately three days for fluindione). (See "Warfarin
and other VKAs: Dosing and adverse effects", section on 'Warfarin administration'.)
For a procedure that requires more rapid normalization of the INR, additional interventions
may be needed to actively reverse the anticoagulant. (See 'Urgent/emergency invasive
procedure' below.)
This discontinuation schedule will produce a period of several days with subtherapeutic
anticoagulation. As an example, it is estimated that if warfarin is withheld for five days
before surgery and is restarted as soon as possible afterwards, patients would have a
subtherapeutic INR for approximately eight days (four days before and four days after
surgery) [14]. Thus, for patients at very high or high thromboembolic risk, bridging may
be appropriate.
●Use of bridging preoperatively – We generally reserve bridging for individuals
considered at very high or high risk of thromboembolism (eg, recent [within the prior three
months] stroke, mechanical heart valve, CHA2DS2-VASc score of 7 or 8 (table 3)
(calculator 1), CHADS2 score of 5 or 6) if they require interruption of warfarin. In these
cases, the bridging agent (eg, therapeutic-dose subcutaneous low molecular weight [LMW]
heparin) is started three days before surgery. (See 'Bridging anticoagulation' below.)
A bridging agent may also be appropriate if there is a prolonged period during which the
patient cannot take oral medications (eg, postoperative ileus) and in patients who have had
a thromboembolic event during a prior episode of perioperative anticoagulant interruption.
This practice is based on expert opinion and has not been formally evaluated in a clinical
trial.
●Restarting warfarin and postoperative bridging – We resume warfarin 12 to 24 hours
after surgery, typically the evening of the day of surgery or the evening of the day after
 surgery, assuming there were no unexpected surgical issues that would increase bleeding
risk and the patient is taking adequate oral fluids [8]. We use the same dose the patient was
receiving preoperatively.
After warfarin is restarted in the perioperative setting, it takes 5 to 10 days to attain a full
anticoagulant effect as measured by an INR above 2. Thus, we generally treat individuals
at very high risk and some individuals with a high risk of thromboembolism with a heparin
bridging agent during this period. (See 'Bridging anticoagulation' below.)
DOAC interruptions (overview) — Individuals who interrupt therapy with a direct oral
anticoagulant (DOAC) will have a shorter period without anticoagulation than those who
interrupt therapy with warfarin, due to the rapid resolution of anticoagulant effect when a DOAC
is discontinued preoperatively and the rapid resumption of effect when a DOAC is restarted
postoperatively.
The PAUSE (Perioperative Anticoagulation Use for Surgery Evaluation) study, which
prospectively evaluated outcomes in 3007 individuals who were taking a DOAC for atrial
fibrillation and underwent an elective surgery or procedure and followed a simple, standardized
management approach for interruption of their anticoagulant [50]. There was no preoperative
coagulation testing and no heparin bridging.

Rates of thromboembolic and hemorrhagic complications associated with this management were
low (major bleeding in <2 percent; ischemic stroke in <0.5 percent), thereby supporting the
safety of this approach. In addition, there was approximately 94 percent adherence to the
preoperative and postoperative DOAC interruption and resumption protocols, thereby supporting
the generalizability of this approach.

The PAUSE approach is illustrated in the figure (figure 1) and summarized as follows:
●Low/moderate bleed risk – For low/moderate bleeding risk surgery, omit the DOAC
one day before and resume one day (approximately 24 hours) after the procedure, provided
hemostasis is secure. The total duration of interruption is two days.
●High bleed risk – For high bleeding risk surgery, omit the DOAC two days before and
resume two days (approximately 48 hours) after the procedure, provided hemostasis is
secure. The total duration of interruption is four days. Waiting an additional one day
before resumption may be appropriate in some cases.
●Impaired kidney function – For individuals with impaired kidney function (creatinine
clearance [CrCl] <30 to 50 mL/min) who are taking dabigatran, there is an additional one
day interruption before low/moderate bleeding risk procedures and an additional two days
interruption before high bleeding risk procedures. Direct factor Xa inhibitors
(apixaban, edoxaban, rivaroxaban) do not require adjustments for kidney function.
Using this approach, residual DOAC levels (not required in routine practice) were in a low range
(<50 ng/mL) in most patients overall, and in 99 percent of patients having a high bleeding risk
surgery [50]. This approach is outlined in more detail in the following sections.
The population in the PAUSE study was exclusively individuals with atrial fibrillation. The
perioperative management from PAUSE can also be applied to patients who are receiving
DOAC therapy for venous thromboembolism (VTE) and require treatment interruption for an
elective procedure (algorithm 1). For individuals in whom the VTE was >30 days prior,
management can be followed in the same manner as individuals with atrial fibrillation. For those
who had a recent VTE (within the prior 30 days), perioperative management should be
individualized and may include placement of a temporary inferior vena cava (IVC) filter or
shorter periods of DOAC interruption. (See 'Temporary IVC filters' above.)
Dabigatran — Dabigatran is a direct thrombin inhibitor; it reversibly blocks the enzymatic
function of thrombin in converting fibrinogen to fibrin.
●Discontinuation – Dabigatran can be omitted for one day before a low/moderate
bleeding risk surgical procedure and for two days before a high bleeding risk procedure, in
individuals with normal or mildly impaired kidney function (CrCl >50 mL/min) (figure 1).
For those with impaired kidney function (CrCl 30 to 50 mL/min), dabigatran can be
omitted for two days before a low/moderate bleeding risk procedure and four days before a
high bleeding risk procedure.
As an example, in a patient on dabigatran with a CrCl >50 mL/min undergoing a high
bleeding risk procedure, the patient will skip four doses of dabigatran (no drug on surgical
day minus 2 and day minus 1) and no drug on the day of surgery (table 5). In dabigatran-
treated patients with a CrCl 30 to 50 mL/min undergoing a high bleeding risk procedure
such as neuraxial anesthesia, a longer interval for interruption is required. (See 'Neuraxial
anesthesia' below.)
The last preoperative day on which dabigatran is administered can be more closely
estimated based on the elimination half-life of dabigatran, which varies according to
kidney function (eg, 12 to 14 hours in patients with normal kidney function) [2,51-54]. A
protocol incorporating bleeding risk and CrCl was tested in a prospective cohort of 541
dabigatran-treated patients undergoing surgery and was associated with low rates of
bleeding and thrombotic complications [54].
Routine coagulation tests have not been validated for ensuring that dabigatran effect has
resolved. A normal or near-normal activated partial thromboplastin time (aPTT) may be
used in selected patients to evaluate whether dabigatran has been adequately cleared from
the circulation prior to surgery (eg, patients at high risk of surgical bleeding) (table 6).
Importantly, the reliability of aPTT testing may depend on the specific assay used; if
available, a diluted plasma thrombin time may be preferable [52,55,56]. (See "Direct oral
anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse
effects", section on 'Dabigatran' and "Clinical use of coagulation tests".)
●Use of bridging – In general, the rapid offset and onset of dabigatran activity makes
bridging anticoagulation unnecessary. We reserve bridging anticoagulation for selected
individuals who are at very high risk for postoperative thromboembolism and require
extended interruption of dabigatran. Examples include postoperative bridging in patients
who are unable to take oral medications postoperatively due to intestinal ileus from
gastrointestinal surgery. (See 'Bridging anticoagulation' below.)
●Restarting dabigatran – Dabigatran should be resumed postoperatively when hemostasis
has been achieved, at the same dose the patient was receiving preoperatively. In general,
dabigatran can be restarted one day (approximately 24 hours) after a low/moderate
bleeding risk surgery/procedure and two days (approximately 48 hours) after a high
bleeding risk surgery/procedure. Since dabigatran has a rapid onset of action, with peak
effects occurring two to three hours after intake, caution should be used in patients who
have had major surgery or other procedures associated with a high bleeding risk. In cases
where the resumption of dabigatran is delayed for two to three days and there is concern
about patients being exposed to an increased risk for VTE, we usually administer a low-
dose LMW heparin regimen (eg, enoxaparin 40 mg daily) until the DOAC is resumed.
If this schedule is used, most patients will omit dabigatran for two total days for a low/moderate
bleeding risk procedure and four total days for a high bleeding risk procedure. An additional one
to two days of dabigatran interruption is done in patients with moderately impaired kidney
function (CrCl 30 to 50 mL/min).
Rivaroxaban — Rivaroxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic
function of factor Xa in converting prothrombin to thrombin.
●Discontinuation – Rivaroxaban can be omitted for one day in patients who are having a
low/moderate bleeding risk surgical procedure and for two days before a high bleeding
risk procedure (figure 1). Thus, for low/moderate bleeding risk procedures, the patient will
omit one dose of rivaroxaban on the one day before the procedure; for high bleeding risk
procedures, the patient will omit two doses of rivaroxaban on the two days before the
procedure. These intervals are based on an elimination half-life of 7 to 11 hours and apply
to individuals with normal kidney function or mildly impaired kidney function (CrCl >50
mL/min), who are likely to be receiving the 20 mg once daily dose; and to those with
moderately reduced kidney function (CrCl 30 to 50 mL/min), who are likely to be
receiving the 15 mg once daily dose.
Longer intervals for interruption may be required for situations in which the bleeding risk
is very high, such as neuraxial anesthesia. (See 'Neuraxial anesthesia' below.)
Rivaroxaban interacts with dual inhibitors of CYP-3A4 and P-glycoprotein (eg,
systemic ketoconazole, ritonavir); dose adjustment or substitution of heparin may be
appropriate if these dual CYP-3A4 and P-glycoprotein inhibitors are used perioperatively.
Interactions with drugs that inhibit only one of these enzymes do not seem to alter
rivaroxaban anticoagulant effect.
Routine coagulation tests have not been validated for ensuring that
the rivaroxaban anticoagulant effect has resolved. A normal or near-normal anti-factor Xa
activity level may be used in selected patients to evaluate whether rivaroxaban has been
adequately cleared from the circulation prior to surgery (eg, patients at high risk of
surgical bleeding) (table 6) [2]. The reliability of anti-factor Xa activity testing may
depend on the specific assay used, and clinicians are advised to speak with their clinical
laboratory to determine whether this assay is available at their institution and whether it
has been validated for direct factor Xa inhibitors.
●Use of bridging – In general, the rapid offset and onset of rivaroxaban makes bridging
anticoagulation unnecessary. In rare cases bridging may be required, such as the use of
postoperative bridging in individuals who have a very high thromboembolic risk and are
unable to take oral medications postoperatively due to intestinal ileus from gastrointestinal
surgery. (See 'Bridging anticoagulation' below.)
●Restarting rivaroxaban – Rivaroxaban can be resumed postoperatively when hemostasis
has been achieved, at the same dose the patient was receiving preoperatively. In general,
rivaroxaban can be restarted one day after a low/moderate bleeding risk procedure and two
days after a high bleeding risk procedure. Since rivaroxaban has a rapid onset of action,
caution should be used in patients who have had major surgery or other procedures
associated with a high bleeding risk. We generally restart rivaroxaban one day after low
bleeding risk surgery and two to three days after high bleeding risk surgery. In cases where
the resumption of rivaroxaban is delayed for two to three days and there is concern about
patients being exposed to an increased risk for VTE, we usually administer a low-dose
LMW heparin regimen (eg, enoxaparin 40 mg daily) until the DOAC is resumed.
If this schedule is used, most patients will omit rivaroxaban for two total days for a low/moderate
bleeding risk procedure and four total days for a high bleeding risk procedure. Adjustments are
not made routinely for patients with moderately impaired kidney function (CrCl 30 to 50
mL/min).
Apixaban — Apixaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic function
of factor Xa in converting prothrombin to thrombin.
●Discontinuation – Apixaban can be omitted for one day before a low/moderate bleeding
risk procedure and for two days before a high bleeding risk procedure (figure 1). Thus, for
low/moderate bleeding risk procedures, the patient will omit two dose of apixaban on the
one day before the procedure; for high bleeding risk procedures, the patient will omit four
doses of apixaban on the two days before the procedure. These intervals are based on an
apixaban elimination half-life of 8 to 12 hours. These intervals apply to individuals with
normal kidney function or mildly impaired kidney function (CrCl >50 mL/min), who are
likely to be receiving the 5 mg twice daily dose; and to those with moderate to severe
kidney insufficiency (CrCl 30 to 50 mL/min), who are likely to be receiving the 2.5 mg
twice daily dose.
Longer intervals for interruption may be required for situations in which the bleeding risk
is very high, such as neuraxial anesthesia. (See 'Neuraxial anesthesia' below.)
Routine coagulation tests have not been validated for ensuring that apixaban effect has
resolved. A normal or near-normal anti-factor Xa activity level may be used in selected
patients to evaluate whether apixaban has been adequately cleared from the circulation
prior to surgery (eg, patients at high risk of surgical bleeding) (table 6). The reliability of
anti-factor Xa activity testing may depend on the specific assay used, and clinicians are
advised to speak with their clinical laboratory to determine whether this assay is available
at their institution and whether it has been validated for direct factor Xa inhibitors.
●Use of bridging – In general, the rapid offset and onset of apixaban makes bridging
anticoagulation unnecessary. In rare cases, bridging may be required, such as the use of
postoperative bridging in individuals who have a very high thromboembolic risk and are
unable to take oral medications postoperatively due to intestinal ileus from gastrointestinal
surgery. (See 'Bridging anticoagulation' below.)
●Restarting apixaban – Apixaban can be resumed postoperatively when hemostasis has
been achieved, at the same dose the patient was receiving preoperatively. In general,
apixaban can be restarted one day after a low/moderate bleeding risk procedure and two
days after a high bleeding risk procedure. Since apixaban has a rapid onset of action,
caution should be used in patients who have had major surgery or other procedures
associated with a high bleeding risk. We generally restart apixaban one day after
low/moderate bleeding risk surgery and two days after a high bleeding risk surgery. In
cases where the resumption of apixaban is delayed for two to three days and there is
concern about patients being exposed to an increased risk for VTE, we usually administer
a low-dose LMW heparin regimen (eg, enoxaparin 40 mg daily) until the DOAC is
resumed.
If this schedule is used, most patients will omit apixaban for two total days for a low/moderate
bleeding risk procedure and four total days for a high bleeding risk procedure. Adjustments are
not made routinely for patients with moderately impaired kidney function (CrCl 30 to 50
mL/min).
Edoxaban — Edoxaban is a direct factor Xa inhibitor; it reversibly blocks the enzymatic
function of factor Xa in converting prothrombin to thrombin.
●Discontinuation – Edoxaban can be omitted for one day before a low/moderate bleeding
risk procedure and for two days before a high bleeding risk procedure (figure 1). Thus, for
low/moderate bleeding risk procedures, the patient will omit one dose of edoxaban on the
one day before the procedure; for high bleeding risk procedures, the patient will omit two
doses of edoxaban on the two days before the procedure. These intervals are based on an
edoxaban elimination half-life of 10 to 14 hours. These intervals apply to individuals with
normal kidney function or mildly impaired kidney function(CrCl >50 mL/min) and those
with moderately impaired kidney function (CrCl 30 to 50 mL/min), who are likely to be
receiving the 60 mg once daily or the 30 mg once daily doses, respectively.
Longer intervals for interruption may be considered for those undergoing major surgery,
neuraxial anesthesia or manipulation, or other situations in which complete hemostatic
function may be required. (See 'Neuraxial anesthesia' below.)
Routine coagulation tests have not been validated for ensuring that edoxaban effect has
resolved. A normal or near-normal anti-factor Xa activity level may be used in selected
patients to evaluate whether edoxaban has been adequately cleared from the circulation
prior to surgery (eg, patients at high risk of surgical bleeding) (table 6). The reliability of
anti-factor Xa activity testing may depend on the specific assay used, and clinicians are
advised to speak with their clinical laboratory to determine whether this assay is available
at their institution and whether it has been validated for direct factor Xa inhibitors.
●Use of bridging – In general, the rapid offset and onset of edoxaban makes bridging
anticoagulation unnecessary. In rare cases, bridging may be required, such as the use of
postoperative bridging in individuals who have a very high thromboembolic risk and are
unable to take oral medications postoperatively due to intestinal ileus from gastrointestinal
surgery. (See 'Bridging anticoagulation' below.)
●Restarting edoxaban – Edoxaban can be resumed postoperatively when hemostasis has
been achieved, at the same dose the patient was receiving preoperatively. In general,
edoxaban can be restarted one day after a low/moderate bleeding risk procedure and two
days after a high bleeding risk procedure. Since edoxaban has a rapid onset of action,
caution should be used in patients who have had major surgery or other procedures
associated with a high bleeding risk. We generally restart edoxaban one day after low
bleeding risk surgery and two to three days after high bleeding risk surgery. In cases where
the resumption of edoxaban is delayed for two to three days and there is concern about
patients being exposed to an increased risk for VTE, we usually administer a low-dose
LMW heparin regimen (eg, enoxaparin 40 mg daily) until the DOAC is resumed.
If this schedule is used, most patients will omit edoxaban for two total days for a low/moderate
bleeding risk procedure and four total days for a high bleeding risk procedure.

BRIDGING ANTICOAGULATION Bridging anticoagulation involves the

administration of a short-acting anticoagulant, typically a low molecular weight (LMW) heparin,

during the interruption of a longer-acting agent, typically warfarin.
Limited indications for bridging — The intent of bridging is to minimize the time the patient is
not anticoagulated, thereby minimizing the risk for perioperative thromboembolism. However,
this needs to be balanced with the importance of mitigating the risk of postoperative bleeding.
Accumulating evidence suggests that in the vast majority of patients, bridging does not provide a
benefit in lowering thromboembolic risk, whereas most data show a consistent increase in
bleeding risk. Our approach to the use of bridging is depicted in the algorithm (algorithm 1) and
summarized as follows:
●Avoid bridging in individuals who have low thromboembolic risk with anticoagulant
interruption [57]:
•Individuals receiving a direct oral anticoagulant (DOAC), unless they have a high
thromboembolic risk and a prolonged period during which they cannot take the DOAC
postoperatively (eg, due to intestinal ileus)
•Routine prophylactic anticoagulation in atrial fibrillation
•Secondary prophylaxis following venous thromboembolism (VTE) (more than three
months prior)
●Bridging may be appropriate during warfarin discontinuation in the following individuals
[1,57]:
•Mechanical mitral valve; mechanical aortic valve with additional stroke risk factors
(see "Antithrombotic therapy for prosthetic heart valves: Management of bleeding and
invasive procedures", section on 'Our approach')
•Embolic stroke within the previous three months or very high stroke risk (eg,
CHADS2 score of 5 or 6)
•VTE within the previous three months (except those with a calf deep vein thrombosis
(DVT) and no evidence of DVT on repeat ultrasound, who may not require bridging)
•Possibly in selected individuals with recent coronary stenting (eg, within the previous
three months) (see "Periprocedural management of antithrombotic therapy in patients
receiving long-term oral anticoagulation and undergoing percutaneous coronary
intervention")
•Previous thromboembolism during interruption of chronic anticoagulation (based on
presumed increased risk; not addressed in clinical trials)
Individuals with valvular atrial fibrillation (or associated with mitral valvular heart disease) have
not been included in large trials, and there may be cases in which the clinician who best knows
the patient may have greater concerns about thrombosis and may decide that bridging is
appropriate. We feel more strongly about avoiding bridging the lower the patient's baseline
thromboembolic risk (eg, lower CHADS2 or CHA2DS2-VASc score (table 3)) and the higher the
risk of bleeding.
Evidence to support the limited use of bridging to selected individuals with very high
thromboembolic risk comes from several meta-analyses. As an example, a 2020 meta-analysis
that included six randomized trials and 12 cohort studies found that bridging was associated with
an increased risk of bleeding (relative risk [RR] 2.83; 95% CI 2.00-4.01) with no statistical
reduction in thromboembolic risk (RR 1.26; 95% CI 0.61-2.58) [58].

Supporting evidence for the practice of avoiding bridging in most individuals with atrial
fibrillation includes the following:

●In the BRIDGE trial (Bridging Anticoagulation in Patients who Require Temporary
Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery), which
randomly assigned 1884 patients with atrial fibrillation who required interruption of
warfarin for an invasive procedure to receive bridging anticoagulation with the LMW
heparin dalteparin versus placebo, the incidence of arterial thromboembolic events 30 days
 after the procedure was similar in those who received dalteparin or placebo (0.3 versus 0.4
percent) [59]. The incidence of major bleeding (a secondary outcome) was higher in those
who received dalteparin (3.2 versus 1.3 percent), although none of the bleeds were fatal.
Patients were excluded from the trial if they had a mechanical heart valve or a recent
(within previous 12 weeks) stroke, embolism, or transient ischemic attack.
●Bridging versus no bridging did not affect major outcomes in patients who required a
major procedure during participation in large anticoagulation trials for atrial fibrillation,
including the RE-LY (warfarin versus dabigatran), ROCKET-AF (warfarin
versus rivaroxaban), and ARISTOTLE (warfarin versus apixaban) trials [9-11]. In the RE-
LY trial, patients receiving warfarin had more thromboembolic events associated with
bridging than with non-use of bridging (1.8 versus 0.3 percent); patients who received
bridging also had a higher risk of major bleeding (warfarin: 6.8 percent with bridging, 1.6
percent without; dabigatran: 6.5 percent with bridging, 1.8 percent without) [60].
●Additional real world data come from the ORBIT-AF and Dresden registries. ORBIT-AF
(Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) is a community-
based registry of outpatients with atrial fibrillation receiving any oral anticoagulant; in this
study, 2200 of 7372 individuals (30 percent) had interruption of anticoagulation for a
procedure [61]. Bridging was used in 24 percent of these interruptions, especially in
patients with a history of stroke or a mechanical heart valve and/or receiving warfarin;
bleeding events were more common in individuals who received bridging compared with
those who did not receive bridging (5 versus 1.3 percent). A composite endpoint that
included major bleeding, myocardial infarction, stroke, systemic embolism,
hospitalization, or death within 30 days was also higher in those who received bridging (13
versus 6.3 percent). In the Dresden NOAC registry, over 800 patients who were
receiving dabigatran, rivaroxaban, or apixaban for any indication and underwent an
invasive procedure had similar rates of major cardiovascular events if they received
bridging, no bridging, or no anticoagulant discontinuation [62]. Bridging was not an
independent risk factor for major bleeding; however, individuals undergoing major
procedures were more likely to receive bridging and to have major bleeding.

Supporting evidence for the practice of avoiding bridging in other groups includes the following:

●VTE – In a systematic review from 2019 that evaluated patients who were receiving
a vitamin K antagonist to treat venous thromboembolism (VTE; 28 cohort studies that
included nearly 7000 procedures), the pooled incidence of recurrent VTE was similar with
and without bridging [63]. The risk of bleeding was generally higher when bridging was
used.
●Any indication for anticoagulation – In a large systematic review and meta-analysis
involving 34 studies (33 observational and one randomized) in patients receiving a vitamin
K antagonist for any indication who were undergoing elective surgery or procedures. there
was no significant difference in the rate of thromboembolism in patients who received
bridging compared with patients who did not (odds ratio [OR] 0.80; 95% CI 0.42-1.54)
[64]. Bridging was associated with a threefold increase in major bleeding compared with
no bridging (OR 3.60; 95% CI 1.52-8.50); full-dose heparin was associated with an
increase in overall bleeding compared with lower heparin doses (OR 2.28; 95% CI 1.27-
4.08). (See 'Heparin product and dose' below.)
A potential role for bridging in reducing the risk of "rebound hypercoagulability" has also been
proposed; however, this premise is not supported by data from the BRIDGE trial discussed
above [59].
Heparin product and dose — Typically, LMW heparins are used for bridging, as they have
similar efficacy compared with unfractionated heparin, are more convenient to use, and generally
do not require monitoring. Intravenous unfractionated heparin is less costly and can be reversed
more rapidly than subcutaneous LMW heparin; it may be a reasonable alternative in some
individuals.
●We prefer LMW heparin for bridging anticoagulation in individuals with a very high risk
of arterial thromboembolism (eg, rheumatic heart disease, atrial fibrillation with recent
embolic stroke, high-risk mechanical heart valve) and those with a moderate risk of
thromboembolism (eg, active cancer) [27,28,65].
Perioperative anticoagulation management in individuals with prosthetic heart valves is
discussed in detail separately. (See "Antithrombotic therapy for prosthetic heart valves:
Management of bleeding and invasive procedures", section on 'Management of
antithrombotic therapy for invasive procedures'.)
●For individuals with impaired kidney function and/or those requiring hemodialysis,
intravenous or subcutaneous unfractionated heparin can be used more easily because
dosing is unaffected by kidney function [66]. (See "Heparin and LMW heparin: Dosing
and adverse effects", section on 'LMW heparin standard dosing'.)

There are no data on using the direct oral anticoagulants (DOACs) as bridging agents. We do not
use any of the DOACs for bridging.

Heparins can be dosed at prophylactic doses, therapeutic doses, or doses intermediate between
the two. The term "therapeutic dose" refers to doses typically used for treatment of
thromboembolic disease, despite the fact that in this case it is being used prophylactically (to
prevent thromboembolism). There are no clinical trial data or practice standards to guide dosing,
and clinical judgment is required to determine the appropriate dose for each patient [64,67,68].
●Therapeutic dosing – Therapeutic dosing (also called "full dose") is appropriate for
bridging anticoagulation for individuals with a potential arterial thromboembolic source
(eg, atrial fibrillation, mechanical heart valve) or VTE within the preceding month.
Typical regimens include enoxaparin, 1 mg/kg subcutaneously twice daily or dalteparin,
100 units/kg subcutaneously twice daily.
●Intermediate dosing – Intermediate-dose anticoagulation may be appropriate for
individuals with atrial fibrillation or VTE within the preceding month when bridging is
needed but concerns about bleeding are greater. Typical regimens include enoxaparin, 40
mg twice daily, or dalteparin, 5000 units subcutaneously twice daily.
●Prophylactic dosing – Prophylactic-dose anticoagulation (also called "low dose")
generally is not used for bridging in patients with atrial fibrillation, because there is no
evidence that prophylactic-dose heparin prevents stroke in this setting. This dose level may
be reasonable in patients who have had a VTE event within the preceding 3 to 12 months.
Typical prophylactic regimens include enoxaparin, 40 mg once daily, or dalteparin, 5000
units subcutaneously once daily.
The use of prophylactic-dose heparin for postoperative VTE prevention in patients not
receiving ongoing anticoagulation is discussed separately. (See "Prevention of venous
thromboembolic disease in adult nonorthopedic surgical patients".)
Additional details regarding heparin products, including dose adjustments for obesity and
impaired kidney function, are provided separately. (See "Heparin and LMW heparin: Dosing and
adverse effects".)
Timing of bridging — Once a decision to use bridging has been made, the next decision is
whether to use bridging before the procedure, after the procedure, or both (table 7). Sample
bridging protocols are provided on the Thrombosis Canada website.
●Atrial fibrillation – As noted above, we suggest not using bridging for most patients
with atrial fibrillation. (See 'Limited indications for bridging' above.)
However, for individuals for whom bridging is used due to a very high risk of
thromboembolism, we use bridging both preoperatively and postoperatively
[14]. Warfarin is usually resumed 12 to 24 hours after surgery, typically the evening of the
day of surgery or the evening of the day after surgery, as long as adequate hemostasis has
been achieved. (See 'Warfarin interruption' above.)
●Venous thromboembolism
•First three months – For individuals within the first three months after an acute
episode of VTE, we use bridging both preoperatively and postoperatively, typically
with therapeutic-dose LMW heparin (eg, enoxaparin 1 mg/kg twice daily) [14]. This
practice is based on the high incidence of recurrence without anticoagulation. While
postoperative intravenous heparin doubles the rate of bleeding, there is a net reduction
in serious morbidity in such patients because the risk of postoperative recurrent VTE is
high. (See 'Preoperative timing of bridging' below and 'Postoperative timing of
bridging' below.)
In selected patients in whom surgery cannot be delayed beyond the first month after
the diagnosis of an acute VTE, it may be appropriate to use a temporary inferior vena
cava (IVC) filter, especially if bridging anticoagulation cannot be used postoperatively
due to high bleeding risk. (See "Overview of the treatment of lower extremity deep
vein thrombosis (DVT)", section on 'Patients with contraindications to
anticoagulation' and "Treatment, prognosis, and follow-up of acute pulmonary
embolism in adults", section on 'Inferior vena cava filters'.)
•Greater than three months – For individuals greater than three months after an acute
episode of VTE, we generally use postoperative bridging, typically with a low-dose
LMW heparin regimen (eg, enoxaparin 40 mg daily), but not preoperative bridging
[69]. For patients who are undergoing a minor procedure or day surgery, bridging is
probably not justified. This practice is based on the significantly reduced risk of VTE
recurrence after the first month [70,71]. (See 'Postoperative timing of bridging' below.)
Preoperative timing of bridging — We generally initiate heparin bridging three days before a
planned procedure (ie, two days after stopping warfarin), when the prothrombin
time/international normalized ratio (PT/INR) has started to drop below the therapeutic range.
●LMW heparin – We discontinue low molecular weight (LMW) heparin 24 hours before
the planned surgery or procedure, based on a biologic half-life of most subcutaneous
LMW heparins of approximately three to five hours [8,65,72]. If a twice-daily LMW
heparin regimen is given, the evening dose the night before surgery is omitted, whereas if
a once-daily regimen is given (eg, dalteparin 200 international units/kg), one-half of the
total daily dose is given on the morning of the day before surgery. This ensures that no
significant residual anticoagulant will be present at the time of surgery, based on studies
that have shown a residual anticoagulant effect at 24 hours after stopping therapeutic-dose
 LMW heparin, and it is consistent with the 2012 American College of Chest Physicians
(ACCP) Guidelines [8,12,73,74].
●Unfractionated heparin – For therapeutic-dose unfractionated heparin, we continue the
intravenous infusion until four to five hours before the procedure, based on the biologic
half-life of intravenous unfractionated heparin of approximately 45 minutes [8,72,73]. If
subcutaneous unfractionated heparin is used, typically with a dose of approximately 250
international units/kg twice daily, the last dose can be given the evening before the
procedure.
Postoperative timing of bridging — Postoperative resumption of unfractionated heparin and
LMW heparin is similar, based on the onset of anticoagulation at approximately one hour after
administration for both forms of heparin, and peak anticoagulant activity at approximately three
to five hours.
●The resumption of bridging, especially when given as a therapeutic-dose regimen, should
be delayed until there is adequate hemostasis based on a clinical assessment of the wound
site, drainage fluid amount, and expected postoperative bleeding; coupled, where
appropriate, with hemoglobin levels [75]. This assessment will vary depending on the
surgery type and individual patient considerations, and it may be difficult for surgery
where ongoing bleeding is not readily apparent (eg, cardiac, intracranial).
●A slight delay in resumption of postoperative anticoagulation is preferable to premature
initiation of postoperative bridging that results in bleeding, which ultimately will lengthen
the period without an anticoagulant and thus increase thromboembolic risk.
●For those undergoing major surgery or those with a high bleeding risk procedure,
therapeutic-dose unfractionated heparin or LMW heparin should be delayed for 48 to 72
hours after hemostasis has been secured [8].
●For most minor procedures associated with a low bleeding risk in which bridging is used
(eg, laparoscopic hernia repair), therapeutic-dose unfractionated heparin or LMW heparin
can usually be resumed 24 hours after the procedure.
Resumption of bridging anticoagulation too early, especially the use of therapeutic-dose heparin
within 24 hours after surgery, is associated with a two- to fourfold increased risk for major
bleeding compared with no bridging or prophylactic-dose heparin. The increased bleeding risk
was demonstrated in the Prospective peri-operative enoxaparin cohort trial (PROSPECT), which
evaluated bleeding risk in a cohort of 260 patients undergoing major surgery whose treating
clinicians used bridging anticoagulation [76]. In this trial, nine patients had major postoperative
bleeding (3.5 percent), most on postoperative day 0, and 19 (7.3 percent) had minor bleeding.
Postoperatively, warfarin is generally resumed on the same postoperative day as the heparin.
Heparin can be discontinued when the INR reaches the therapeutic range for individuals at
moderate thromboembolism risk.
Individuals with heparin-induced thrombocytopenia — Heparin-induced thrombocytopenia
(HIT) is a potentially life-threatening condition in which heparin-induced antibodies to platelets
can cause thrombocytopenia and/or venous or arterial thrombosis. (See "Clinical presentation
and diagnosis of heparin-induced thrombocytopenia".)
Patients with HIT should not receive any heparin (eg, they should not receive heparin
flushes, unfractionated heparin, or LMW heparin). Nonheparin anticoagulants that can be used in
patients with HIT are discussed separately. (See "Management of heparin-induced
thrombocytopenia", section on 'Anticoagulation'.)
 URGENT/EMERGENCY INVASIVE PROCEDURE Reversal of the patient's usual

anticoagulant may be required for more urgent or emergency surgery or procedures or to treat
perioperative bleeding. Agents with a potential prothrombotic effect (eg, prothrombin complex
concentrates [PCCs], plasma products, immediate reversal agents) should be reserved for the
treatment of severe, life-threatening bleeding or anticipated severe bleeding (eg, intracranial
hemorrhage, emergency major surgery with elevated prothrombin time/international normalized
ratio [PT/INR]). Agent-specific strategies include the following:
●Warfarin – For individuals who require reversal of warfarin or other vitamin K
antagonists, the appropriate reversal strategy is determined by the degree of
anticoagulation (eg, PT/INR, clinical bleeding), urgency of the procedure, and degree of
bleeding risk (table 8).
•If semi-urgent reversal of warfarin is required (eg, within one to two days), warfarin
should be withheld and vitamin K administered (eg, 2.5 to 5 mg of oral or intravenous
vitamin K). (See "Management of warfarin-associated bleeding or supratherapeutic
INR", section on 'Urgent surgery/procedure'.)
•If immediate reversal is required (eg, for emergency surgery or active bleeding), this
can be achieved via the use of PCCs or plasma products (eg, Fresh Frozen Plasma
[FFP], Plasma Frozen Within 24 Hours After Phlebotomy [PF24]) along with vitamin
K (table 9) [77,78]. The 4-factor PCCs contain adequate amounts of all vitamin K-
dependent clotting factors, whereas 3-factor PCCs may require supplementation with
FFP for adequate factor VII (table 10). Of note, there is a thrombotic risk associated
with these products, and they should be used only if there is life-threatening bleeding
and prolongation of the INR by a vitamin K antagonist [78]. (See "Management of
warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life-
threatening bleeding'.)
●Dabigatran – Dabigatran is an oral direct thrombin inhibitor; it can be reversed
by idarucizumab (table 11). In an open-label study involving 503 patients who had
bleeding or required emergency surgery, idarucizumab effectively reversed the
anticoagulant effect of dabigatran [79]. The use of this agent as well as other potential
strategies for individuals receiving dabigatran who are at great risk of serious bleeding
with an emergency procedure are presented separately. (See "Management of bleeding in
patients receiving direct oral anticoagulants".)
●Rivaroxaban, apixaban, and edoxaban – Rivaroxaban, apixaban, and edoxaban are oral
direct factor Xa inhibitors; these anticoagulants can be reversed by andexanet alfa or a
PCC (table 11). These and other potential strategies for individuals receiving these agents
who are at great risk of serious bleeding with an urgent/emergency procedure are
presented separately. (See "Management of bleeding in patients receiving direct oral
anticoagulants".)
Algorithms for anticoagulant reversal depending on the severity of bleeding are provided by
various societies and groups such as Thrombosis Canada.
Additional discussions of postoperative bleeding are presented separately. (See "Postoperative
complications among patients undergoing cardiac surgery", section on 'Hematologic
dysfunction'.)
 NEURAXIAL ANESTHESIA Neuraxial (ie, spinal or epidural) anesthesia

should not be used in anticoagulated individuals, due to the risk of potentially catastrophic
bleeding into the epidural space. The increased risk of bleeding applies both at the time of
catheter placement and the time of removal.
If neuraxial anesthesia is considered for surgical anesthesia or postoperative pain control, the
timing of anesthesia and anticoagulant administration should be coordinated to optimize the safe
use of both. Early consultation with the anesthesiologist is advised. This subject is discussed in
detail separately. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving
anticoagulant or antiplatelet medication".)
The timing of anticoagulant use in patients receiving neuraxial anesthesia is illustrated by
evidence-based guidelines from the American Society of Regional Anesthesia (ASRA), which
suggest the following [80,81]:
●Prophylactic-dose low molecular weight (LMW) heparin (eg, enoxaparin, 40 mg once
daily):
•Before surgery, wait at least 10 to 12 hours after the last dose of LMW heparin is
administered before a spinal/epidural catheter is placed.
•After surgery, when there is adequate surgical site hemostasis, wait at least six to
eight hours after catheter removal before resuming treatment with LMW heparins.
●Therapeutic-dose LMW heparin (eg, enoxaparin, 1 mg/kg twice daily):
•Before surgery, wait at least 24 hours after the last dose of LMW heparin is
administered before a spinal/epidural catheter is placed.
•After surgery, when there is adequate surgical site hemostasis, for twice daily dosing,
wait at least 24 hours after catheter removal before resuming therapeutic-dose LMW
heparin. For once daily dosing, wait at least six to eight hours after catheter removal
before the first dose; the second postoperative dose should occur no sooner than 24
hours after the first dose.

SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines

from selected countries and regions around the world are provided separately. (See "Society
guideline links: Anticoagulation".)

INFORMATION FOR PATIENTS UpToDate offers two types of patient education

materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written
in plain language, at the 5th to 6th grade reading level, and they answer the four or five key
questions a patient might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more detailed. These articles are written at
the 10th to 12th grade reading level and are best for patients who want in-depth information and
are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a variety
of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Taking medicines for blood clots (The
Basics)" and "Patient education: Choosing a medicine for blood clots (The Basics)")
●Beyond the Basics topics (see "Patient education: Warfarin (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Balancing thromboembolic and bleeding risk – Interruption of anticoagulation

temporarily increases thromboembolic risk, and continuing anticoagulation increases the
risk of bleeding. We take into account these risks, along with specific features of the
anticoagulant the patient is taking. Internet-based resources and case examples are
provided above. (See 'Overview of our approach' above.)
•Thromboembolic risk – Those at very high or high thromboembolic risk should limit
the period without anticoagulation to the shortest possible interval (table 1). If
thromboembolic risk is transiently increased (eg, recent stroke, recent pulmonary
embolism), we prefer to delay surgery until the risk returns to baseline, if possible.
(See 'Estimating thromboembolic risk' above.)
-Atrial fibrillation – We estimate thromboembolic risk for patients with atrial
fibrillation based on clinical variables including age and comorbidities. In the RE-
LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) trial, the
perioperative thromboembolic risk was 1.2 percent based on a composite endpoint
of stroke, cardiovascular death, and pulmonary embolus. The risk of recurrent
arterial embolism from any cardiac source is approximately 0.5 percent per day in
the first month after an acute event. (See 'Atrial fibrillation' above and "Atrial
fibrillation in adults: Use of oral anticoagulants".)
-Prosthetic heart valve – The risks of thromboembolism and perioperative
management of patients with bioprosthetic and mechanical heart valves are
discussed separately. (See "Antithrombotic therapy for prosthetic heart valves:
Management of bleeding and invasive procedures", section on 'Management of
antithrombotic therapy for invasive procedures' and "Diagnosis of mechanical
prosthetic valve thrombosis or obstruction".)
-Recent thromboembolism – The perioperative risk of venous thromboembolism
(VTE) is greatest in individuals with an event within the prior three months, and
those with a history of VTE associated with a high-risk inherited thrombophilia.
Patients who require surgery within the first three months following an episode of
VTE are likely to benefit from delaying elective surgery, even if the delay is only
for a few weeks. (See 'Recent thromboembolism' above.)
•Bleeding risk – A higher bleeding risk confers a greater need for perioperative
hemostasis, and hence a longer period of anticoagulant interruption. Bleeding risk is
dominated by the type and urgency of surgery (table 2); some patient comorbidities
(eg, older age, decreased kidney function) and medications that affect hemostasis also
contribute. (See 'Estimating procedural bleeding risk' above and 'Deciding whether to
interrupt anticoagulation' above.)
 -High risk – High bleeding risk procedures include coronary artery bypass
surgery, kidney biopsy, and any procedure lasting >45 minutes. In general, the
anticoagulant must be discontinued if the surgical bleeding risk is high.
(See 'Settings requiring anticoagulant interruption' above.)
-Low risk – Low bleeding risk procedures include dental extractions, minor skin
surgery, cholecystectomy, carpal tunnel repair, and abdominal hysterectomy.
Individuals undergoing selected low bleeding risk surgery often can continue their
anticoagulant. (See 'Settings in which continuing the anticoagulant may be
preferable' above.)
-Cardiac implantable device or catheter ablation for atrial fibrillation –
Continuing warfarin was associated with a lower risk of bleeding in patients on
the BRUISE CONTROL trial who were undergoing implantation of a cardiac
implantable electronic device (eg, pacemaker, implantable cardioverter-
defibrillator) and patients on the COMPARE trial who were undergoing catheter
ablation for atrial fibrillation. (See 'Overview of whether to interrupt' above
and "Cardiac implantable electronic devices: Periprocedural complications".)
●Timing of interruption – The timing of interruption depends on the periprocedural
bleeding risk and the specific anticoagulant. The algorithm summarizes our approach
(algorithm 1). The figure illustrates the timing of direct oral anticoagulant (DOAC)
interruption (figure 1). (See 'Timing of anticoagulant interruption' above.)
●Bridging – Bridging anticoagulation involves the administration of a short-acting
anticoagulant, typically a low molecular weight (LMW) heparin, during the interruption of
a longer-acting agent, typically warfarin. The intent is to minimize the risk of perioperative
thromboembolism. For most individuals, bridging increases bleeding risk without lowering
thromboembolic risk, and we suggest not using bridging (Grade 2B). We feel more
strongly about avoiding bridging the lower the baseline thromboembolic risk and the
higher the bleeding risk. We generally do not use bridging for DOACs. (See 'Limited
indications for bridging' above.)
For selected patients on warfarin (eg, stroke, systemic embolism, or transient ischemic
attack within the previous three months; atrial fibrillation and very high risk of stroke [eg,
CHADS2 score of 5 or 6]; VTE within the previous three months; recent coronary stenting;
previous thromboembolism during interruption of chronic anticoagulation), we suggest the
use of bridging (Grade 2C).
•Agent – When bridging is used, we prefer LMW heparin for most patients. An
exception is an individual with impaired kidney function and/or hemodialysis
requirement, for whom intravenous or subcutaneous unfractionated heparin can be
used more easily. We do not use DOACs for bridging. Nonheparin anticoagulants that
can be used in patients with heparin-induced thrombocytopenia are discussed
separately. (See 'Heparin product and dose' above.)
•Timing – Bridging can be used preoperatively, postoperatively, or both, depending on
the underlying condition for which the patient is being anticoagulated (table 7). The
timing depends on the heparin product used and the procedural bleeding risk.
Importantly, resumption of bridging anticoagulation too early is associated with an
increased risk for major bleeding. (See 'Timing of bridging' above.)
 The role of bridging in individuals with mechanical heart valves is discussed separately.
(See "Antithrombotic therapy for prosthetic heart valves: Management of bleeding and
invasive procedures".)
●Urgent/Emergency procedure – Reversal of the patient's usual anticoagulant may be
required for more urgent or emergency procedures or to treat perioperative bleeding.
Agents with a potential prothrombotic effect (eg, immediate reversal agents, prothrombin
complex concentrates, plasma products) should be reserved for the treatment of life-
threatening, severe bleeding or anticipated severe bleeding (intracranial hemorrhage,
emergency major surgery). (See 'Urgent/emergency invasive procedure' above
and "Management of bleeding in patients receiving direct oral anticoagulants".)

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Penanganan perdarahan:
1. Penekanan degan tampon yang dibasahi dengan asam traneksamat
2. Debridement, kuret jendalan darah dan irigasi dengan saline
3. Pembuatan flap
4. Insersi local thrombin pada soket, missal spongostan
5. penjahitan bekas luka pencabutan dengan benang absorbable (vicryls 4-0)
 1. assessing the AF related thromboembolic risk (CHADS2 score)
2. assessing the bleeding risk , HES-BLED score

PERIOPERATIVE MANAGEMENT OF DOAC

High risk of tansient ischemic attack:

1. Pasien dengan atrial fibrilasi dan terdapat strke atau transient ischemic attack (>3 bulan
sebelum operasi)
2. Pasien dengan skor CHADS2 <5 yang memiliki riwayat tromboemboli
spongostan will create a barrier together with fibrin which will stop the bleeding in 2–10
minutes and will be completely resorbed in 4–6 weeks.

Surgicel hemostat works in a three step process, which proceeds as follows:

 The surgeon places the Surgicel hemostat on the open wound or damaged tissue and vessels
and compresses the Surgicel dressing for three minutes.
 The hemostat stimulates the production of thrombin and fibrinogen, which facilitates
coagulation of the blood.
 The adhesive properties of the Surgicel hemostat form a seal that prevents bleeding.

In the ISTH survey, 89.6% of respondents agreed that a single consensus term is necessary to
describe the newest oral anticoagulant drug class.4 Although NOAC was the first terminology
used and is now adopted by the CHEST 2016 guidelines, it has major limitations regarding the
meaning of “N” and safety implications.

DOAC seems to be a very reasonable term moving forward that should be embraced by
clinicians to describe these new oral anticoagulants and oral coagulants with similar direct
mechanisms that haven’t yet been released.

Dalam survei ISTH, 89,6% responden setuju bahwa istilah konsensus tunggal diperlukan untuk

menggambarkan kelas obat antikoagulan oral terbaru.4 Meskipun NOAC adalah terminologi
pertama yang digunakan dan sekarang diadopsi oleh pedoman CHEST 2016, ia memiliki

keterbatasan besar mengenai arti "N" dan implikasi keamanan.

DOAC tampaknya menjadi istilah yang sangat masuk akal untuk bergerak maju yang harus

dianut oleh dokter untuk menggambarkan antikoagulan oral dan koagulan oral baru ini dengan

mekanisme langsung serupa yang belum dirilis.

Dalam survei ISTH, 89,6% responden setuju bahwa istilah konsensus tunggal diperlukan untuk

menggambarkan kelas obat antikoagulan oral terbaru.4 Meskipun NOAC adalah terminologi

pertama yang digunakan dan sekarang diadopsi oleh pedoman CHEST 2016, ia memiliki

keterbatasan besar mengenai arti "N" dan implikasi keamanan.

DOAC tampaknya menjadi istilah yang sangat masuk akal untuk bergerak maju yang harus

dianut oleh dokter untuk menggambarkan antikoagulan oral dan koagulan oral baru ini dengan

mekanisme langsung serupa yang belum dirilis.

t
max

(jam) 1,5 (dosis 2,5mg) 2-4 1-6 4

3,3 (dosis 5mg)
3-4 (dosis 10mg)

Farmakodinamik asam traneksamat bekerja pada proses pembekuan darah. Asam

traneksamat merupakan derivat asam amino lisin yang bekerja menghambat proses
fibrinolisis. Asam amino lisin yang memiliki afinitas tinggi akan menempel pada reseptor
plasminogen, sehingga plasmin tidak dapat diaktifkan. Akibatnya proses degradasi fibrin
dan faktor pembekuan lainnya oleh plasmin tidak terjadi.

1. Obat apa yang perlu diperhatikan pada pasien yang mengkonsumsi apixaban
dan apa pengaruhnya
2. Berapa waktu apixaban mencapai dosis maksimal
3. Bagaimana mekanisme kerja asam traneksamat dalam menghambat perdarahan
4. Pada pasien jantung berapa dosis adrenalin yang dianjurkan
5. Kapan apixaban dapat dikonsumsi setelah dilakukan tindakan dan bridging
heparin