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FAAL HEMOSTASIS
Oleh : dr. Diah Hermayanti, SpPK

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TIU

Memahami pemeriksaan faal hemostasis

TIK

Memahami proses hemostasis

Memahami proses hemostasis pada jejas vaskuler

Memahami dan dapat menginterpretasi pemeriksaan laboratorium hemostasis

HEMOSTASIS
Proses fisiologis yg seimbang :
mencegah perdarahan >>> (setelah perlukaan vaskuler) mempertahankan sirkulasi (dg menjaga darah tetap cair) Perdarahan

Trombosis KOAGULASI Perdarahan

HEMOSTASIS
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FIBRINOLISIS Trombosis

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TAHAPAN PROSES BILA TJD TRAUMA VASKULER :

1. Vasokonstriksi
2. Primary hemostasis (detik)

3. Secondary hemostasis (menit)

4. Proses perbaikan & fibrinolisis

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SECONDARY HEMOSTASIS

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PRIM ARY HEMOSTASIS

PROSES HEMOSTASIS
Vascular injury
Exposure of colagen
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Tissue factor
Platelet adhesion & Release reaction

Serotonin

Release of Platelet phopholipid

TX2, ADP

Vasoconstriction

Platelet aggregation

Coagulation cascade

Blood flow

Primary Hemostatic plug

Thrombin

Secondary hemostatic plug (stable hemostatic plug)

Fibrin

Surface contac : HMWK Prekalikrein

JALUR KOAGULASI DARAH

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XII XI IX

XIIa XIa IXa VIIIa X

Ca 2+ Ca
2+

TF + VIIa
JALUR EKSTRINSIK

JALUR INTRINSIK +

VIII

Xa + Va + phospholipid XIII IIa (thrombin) XIIIa I (fibrinogen) Fibrin Crosslinked fibrin

II (prothrombin)

Ca 2+ PL

FAKTOR KOAGULASI PLASMA Faktor I II III IV V VII VIII IX X XI XII XIII Nama

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Fibrinogen Prothrombin Tissue thromboplastin Calcium Proaccelerin (labile factor) Proconvertin (stable factor) Antihemophilic A factor Antihemophilic B factor Stuart factor Plasma thromboplastin antecedent Hageman factor, contact factor Fibrin stabilizing factor

JALUR FIBRINOLISIS
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PLASMINOGEN
Aktivator : o intrinsik : F.XII, kinin, trombin, urokinase oEkstrinsik : t-PA, excercise, stress oTerapeutik : streptokinase Anti aktivator : o C-1 Esterase inhibitor o PAI (plaminogen activator inhibitor )

PLASMIN
Antiplasmin : o 2 antiplasmin o 2 makroglobulin

FIBRIN

FIBRIN DEGRADATION PRODUCTS (FDP)

PEMERIKSAAN LABORATORIUM UNTUK MENILAI FAAL HEMOSTASIS

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TUJUAN PEMBELAJARAN : Memahami prinsip pemeriksaan laboratorik hemostasis sederhana Mengkaitkan dg penyakit gangguan faal hemostasis (interpretasi & diagnostik)

Pendekatan : 1. Anamnesis 2. Pemeriksaan fisik 3. Laboratorik

ENDOTEL MENGATUR FLUIDITAS HEMOSTASIS

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Trombosis Pro-trombotik : trombosit-vaskuler koagulasi plasma

Bleeding Anti-trombotik : antikoagulan inhibitor fibrinolisis

BLOOD FLOW

Bleeding

Trombosis

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ANAMNESIS Eksplorasi riwayat penyakit : keturunan (herediter) didapat (acquired )

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Anamnesa : 1. Perdarahan circumsisi / tali pusat / persalinan ? 2. Epistaksis / memar (easy bruising) ?; persendian (joint bleeding)? 3. Perdarahan cabut gigi ? 4. Menstruasi berkepanjangan ? 5. Memar tanpa sebab yg jelas ? 6. Darah di urin / feses ? 7. Riwayat transfusi (terutama trombosit) ? 8. Minum obat aspirin / derivatnya (7 hari terakhir ) ?

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PEMERIKSAAN FISIK
PTEKIAE

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PURPURA
EKIMOSIS

: bercak merah kecil di kulit ( ujung jarum) (ekstravasasi darah dari vaskuler yg intak karena peningkatan permeabilitas) : kumpulan ptekiae : area lebam (kebiruan) ( > purpura)

HEMATOMA : lebam luas yg menginfiltrasi subkutan atau otot, shg menyebabkan deformitas HEMARTROSIS : perdarahan di persendian (perdarahan berat) gangguan koagulasi (hemofili) HEMATURIA : perdarahan di urin (trauma lokal batu; overdosis antikoagulan; hemofili)

PEMERIKSAAN LABORATORIUM
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TES SKRINING : Jumlah & morfologi trombosit Bleeding time Clotting time aPTT (activated partial thromboplastin time) PT (prothrombin time) menilai primary hemostatic plug

menilai koagulasi / secondary hemostatic plug

TES KONFIRMASI / KHUSUS : Fungsi trombosit (adesi, sekresi, agregasi) Pengukuran faktor koagulan Pemeriksaan inhibitor

TES SKRINING PRIMARY HEMOSTATIC PLUG (TROMBOSIT-VASKULER )

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Tujuan : menentukan kelainan trombosit / vaskuler TROMBOSIT : o morfologi o jumlah o fungsi Capillary resistance test (Rumple-Leed test) Bleeding time (Ivy ; Duke)

RUMPLE LEEDE TEST (Capillary resistance test)

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VOLAR (dibaca 15 menit setelah Tekanan dilepas)

Systole

HASIL : (-) : jumlah ptekiae < 10 10-20 : meragukan (+) : > 20 Diastole

5 minutes
( 100 mmHg)

POSITIF : 1. Trombositopenia 2. Gangguan vaskuler 3. Gangguan fungsi trombosit

BLEEDING TIME / BT (waktu perdarahan)

BT menilai

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Pembentukan hemostatic plug

1. Kelainan trombosit 2. Kelainan vaskuler

Normal (Duke) : 1-3 menit Memanjang : 1. Kelainan konstriksi vaskuler 2. Trombositopenia 3. Gangguan adhesi trombosit 4. Gangguan pelepasan ADP trombosit 5. Gangguan aggregasi trombosit 6. Gangguan avaibilitas PF3

Bleeding Time
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Volar Cuping telinga Cara Normal 1-3 menit

40 mmHg
Cara Normal 1-7 menit

Duke
2 1 2
1

Ivy

Kertas saring

Start

Start
Normal

Dacie et al. 1975, Hirsh et al. 1979, Sirridge et al. 1983

Abnormal (memanjang)

Bleeding time menilai :

TES SKRINING KOAGULASI (secondary hemostatic plug /fibrin clot formation)

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Tujuan : deteksi gangguan koagulasi menentukan tahapan proses yg terganggu

Pemeriksaan : clotting/coagulation time (CT) aPTT (activated partial thromboplastin time) PPT (plasma prothrombin time) TT (thrombin time)

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CLOTTING FACTOR (CT)

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MENILAI WAKTU

pembentukan tahap awal dr thrombin untuk menghasilkan bekuan yg terlihat mata (Jalur intrinsik & jalur umum) - defisiensi faktor pembekuan yg berat pada jalur intrinsik dan jalur umum (common pathway) (Tidak dipengaruhi oleh F VII) - pemakaian heparin Normal : 5-15

CT >>>

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ACTIVATED PARTIAL THROMBOPLASTIN TIME (aPTT)

Tes koagulasi jalur intrinsik (prekalikrein, HMWK, F. XII,XI, IX, VIII) jalur umum (F. X,V, prothrombin, fibrinogen)

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aPTT deteksi : 1. Defisiensi faktor di atas 2. Skrining antikoagulan lupus 3. Monitor terapi heparin

Normal

: 25 - 39 detik (tergantung laboratorium)

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PLASMA PROTHROMBIN TIME (PPT)

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Tes koagulasi Jalur ekstrinsik (F.VII) Jalur umum ( F.X, V, II, I) PPT deteksi : 1. kontrol antikoagulan oral koumarin (F.II, VII, X adalah vit K dependent yg terdepresi oleh obat koumarin) 2. defisiensi F. VII & X

Normal

: 10 -14 detik (tergantung laboratorium)

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INTERNATIONAL NORMALISED RATIO (INR)

Dipergunakan untuk menstandarsisasi hasil pengukuran PPT yg sangat tergantung pada masing-masing laboratorium INR = PTtest
PTnormal
ISI

ISI

: International sensitivity index (tergantung batch)

0,8 -1,2 2 -3 (normal, tanpa terapi antikoagulan) (pengobatan antikoagulan/Warfarin)

Normal :

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THROMBINE TIME (TT)

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Tes koagulasi mengukur kecepatan pembentukan fibrin

TT abnormal : 1. defisiensi F.I (fibrinogen) 2. kelainan kualitatif fibrinogen 3. heparin 4. disseminated intravascular coagulation (DIC)

PENDEKATAN (Anamnesa, fisik, laboratorik)

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Gg.Perdarahan (bleeding disorders)

Gg.Trombosis (thrombotic disorders)

Congenital (herediter)

Acquired (didapat)

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Gg. KOAGULASI (CLOTTING DISORDERS) HEREDITER

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Von Willebrand synd. Hemophilia A (VIII def) Hemophilia B (IX def) Factor XI deficiency Factor II deficiency Factor V deficiency Factor VII deficiency Factor X deficiency Factor XII deficiency Prekallikrein deficiency HMWK deficiency Afibrinogenia

1:200 - 5.000 1:5.000 - 10.000 1:50.000 - 100.000 1:100.000 - 500.000 < 1:106 < 1:106 < 1:106 < 1:106 < 1:106 < 1:106 < 1:106 < 1:106

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Gg. KOAGULASI DIDAPAT (ACQUIRED)

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ACQUIRED DEFICIENCY STATE : Liver disease vit K deficiency oral anticoagulant amyloidosis consumptive coagulopathies hematin snake venom INHIBITION of CLOT FORMATION : Heparin lupus anticoagulant macromolecules neutralizing factor inhibitors (dextran) non- neutralizing factor inhibitors dysfibrinogenemia

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DIFERENSIAL SKRINING KOAGULASI

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Prolonged APTT COMMON Heparin Lupus anticoagulant Hemophilia A Hemophilia B VWD (with long BT) UNCOMMON Specific factor inhibitors F. XI or XII deficiency Prekalikrein def HMWK deficiency

Prolonged PT

Prolonged APTT&PT

Vit K deficiency Oral anticoagulant Liver disease

Vit K deficiency Oral anticoagulant Liver disease Consumptive -coagulopathies

Factor VII deficiency

F. II, V, or X def Hereditary dysfibrinogenemia Afibrinogenemia Specific factorinhibitors Amyloidosis

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GANGGUAN TROMBOSIT

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Gangguan kualitas (trombositopati) : Gangguan kuantitas : Jumlah turun (trombositopenia) : - produksi << - usia <; destruksi > - pooling >> (di Limpa) Jumlah meningkat (trombositosis)
Primer Sekunder

Fungsi yg terganggu :
Adesi Release Agregasi Koagulasi

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KELAINAN TROMBOSIT HEREDITER

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Kelainan
Kelainan adhesi von Willebrand synd Bernard-Soulier synd Collagen disorders Kelainan agregasi Glansmanns thrombasthenia Afibrinogenemia dll

Laboratorium
vWF, Platelet aggregation vWF, Platelet aggregation BT, normal platelet aggregation BT, platelet aggregation, GP IIB-IIIA BT, platelet aggregation, fibrinogen

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KELAINAN TROMBOSIT DIDAPAT (mengganggu fungsi trombosit)

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Obat (aspirin, indometasin, ibuprofen, penisilin) Antibodi trombosit Penyakit ginjal Myeloproliferative disorders Myeloma Fibrinolysis Macromolecules Fibrin split product Monoclonal proteins In vivo release hypothyroidism

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GANGGUAN TROMBOSIS
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HEREDITER Sistem Serine protease inhibitor (SERPINS) Kelainan Defisiensi Antitrombin III Def. Heparin kofaktor II

Sistem fibrinolitik

Def. Protein C heterozygous Def. Protein C homozygous Def. Protein S heterozygous Hyperactive platelet synd
dll

Trombosit
Miscellaneous

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Gangguan Trombotik Didapat

Kondisi sistemik :

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Kelainan hemostatik :

Atherosclerotic vascular disease diabetes mellitus malignat neoplasma myeloproliferative disorders paroxismal nocturnal hemoglobinuria estrogen & oral contraceptive Pregnancy venous stasis nephrotic syndrome hyperlipidemia artificial vascular prostheses hyperviscosity

Lupus anticoagulant DIC Thrombotic thrombocytopenic purpura Hemolytic-uremic synd Snake venoms Coagulation factorconcentrates

COMPLEX HEMOSTATIC DISORDERS

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DISORDER
Disseminated intravascular Coagulation (DIC)

LABORATORY MANIFESTATIONS
thrombocytopenia long PT increased FDPs low fibrinogen long APTT low AT III

Thrombotic thrombocytopenic Purpura (TTP) Hemolytic uremic syndrome (HUS)

thrombocytopenia normal fibrinogen microangiopathic peripheral blood film normal AT III

Liver disease

long PT low AT III normal to low fibrinogen

Brandt 1999

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

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INITIATING STIMULUS ACTIVATION ACTIVATION

THROMBIN

PLASMIN

FIBRIN FORMATION

PLATELET ACTIVATION

FACTOR CONSUMPTION

FIBRINOLYSIS

MICROVASCULAR THROMBOSIS

HEMORRHAGE

FIBRINOGEN DEPLETION

PLATELET DEPLETION Brandt 1999

HEMORRHAGE

DIC STIMULATOR :
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1. Tissue factor coagulants : trauma hemolysis carcinoma

2. Factor producing platelet aggregation : septicemia uremia immune complexes

3. Endothelial damage : burn vasculitis

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GANGGUAN HEMOSTATIK PADA PENYAKIT LIVER

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ABNORMALITAS

MANIFESTASI LABORATORIUM

MANIFESTASI KLINIK

TROMBOSITOPENI

TROMBOSITOPENI

PERDARAHAN

SINTESA FAKTOR KOAGULASI <<<

SINTESA PROTEIN REGULATOR <<< DISFIBRINOGENEMIA

PT & APTT >>>>>

PERDARAHAN

AT III <<, PROTEIN C <<

THROMBOSIS, DIC

TT / PT / APTT >>>>> FDP FALSE (+) PT >>>>

NONE / PERDARAHAN RINGAN PERDARAHAN (?)

ABNORMAL PROTEIN DEPENDEN VIT K

Brandt, 1999

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VITAMIN K DEFICIENCY
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VIT-K dibutuhkan oleh hati untuk sintesa : Vit-K dependent coagulation factors

(F. II , VII, IX, X)

SUMBER VIT-K : - makanan (tu. Tumbuhan) - sifat : fat soluble PENYEBAB DEFISIENSI : - malabsorpsi lemak - obstruksi bilier (gg.sekresi empedu) - pancreatic disease (gg.produksi lipase pankreas)

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RINGKASAN
TES Bleeding time (BT) Capilary resistance test

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MENILAI INTEGRITAS Trombosit Vaskuler

Thrombine time (TT) Prothrombine time (PT) Activated partial thromboplastin time (APTT)

Fibrinogen /fibrine conversion Jalur ekstrinsik Jalur intrinsik

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SEMOGA BERMANFAAT
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