ANTIKOAGULAN PADA

HEMODIALISIS

Dr. Alta Ikhsan Nur

 Pembekuan Darah
Pada Sirkuit Ekstrakorporeal
Darah pasien HD terpapar dengan berbagai alat kanul IV,
tubing, drip chambers , headers, potting compound dan
membran dialisis selama proses dialisi.

Permukaan alat ini

menginisiasi pembekuan
darah

Pembentukan trombus secara

significan cukup untuk
menyebabkan oklusi dan
malfungsi sirkuit
Pembentukan Bekuan dalam Sirkuit
Ekstrakorporeal dimulai dengan Pelapisan
permukaan sirkuit ektracorporeal oleh protein
plasma

Adhesi dan Agregasi Trombosit

Pembentukan Tromboxan A2 dan

Aktivasi Kaskade Koagulasi Intrinsik

Terbentuk trombin dan deposit fibrin

 Faktor-faktor Yang Memudahkan
Pembekuan Sirkuit Ekstrakorporeal
• Aliran darah lambat
• Hematokrit >>>
• Laju ultrafiltrasi tinggi
• Transfusi darah dan
komponen darah
intradialitik
• Intradialisis lipid infusion
• Penggunaan drip chambers
(paparan udara,
pembentukan busa, dan
turbulensi)
Penilaian Koagulasi selama Dialisis

1. Inspeksi visual
2. Tekanan sirkuit ekstrakorporeal
3. Gambaran Dializer setelah Dialisis
4. Pengukuran Volume Residu Dializer
 Penilaian Koagulasi selama Dialisis

1. INSPEKSI VISUAL
Tanda bekuan darah dalam sirkuit
ekstrakorporeal :

• Warna darah sangat gelap

• Bercak bayangan/gelap dalam dializer
• Busa diikuti formasi bekuan dalam
drip chambers dan venous trap
• Darah setelah melalui dializer tidak
dapat masuk ke venous chumber
• Terlihat bekuan dalam arterial header
 Penilaian Koagulasi selama Dialisis

2. Tekanan Sirkuit Ekstrakorporeal

• Keuntungan penggunaan monitor “post-pump

arterial pressure’”pada aliran darah dapat
membedakan antara pembacaan tekanan post-pump
dan vena dalam penentuan lokasi bekuan.
• Bekuan di dializer : tekanan post-pump ⇧, vena ⇩
• Bekuan pada atau distal venous blood chamber :
tekanan keduanya ⇧
• Jika cloting luas  peningkatan tekanan yang tinggi
• Sebuah bekuan atau malposisi jarum vena 
peningkatan tekanan.
 Penilaian Koagulasi selama Dialisis

3. Gambaran Dializer setelah Dialisis

• Pada bagian Header sering terkumpul bekuan-

bekuan darah kecil atau whitish deposit (khususnya
pada pasien dyslipidemia)
• Bekuan yang banyak/bermakna harus dicatat sebagai
parameter untuk pengaturan pemberian dosis Heparin.
• Klasifikasi jumlah bekuan didasarkan pada
perkiraan persentase serat bekuan :
• Grade 1 untuk serat bekuan <10%
• Grade 2 <50%
• Grade 3 >50%
 Penilaian Koagulasi selama Dialisis

4. Pengukuran Volume Residu Dializer :

• Penggunaan reuse Dializer, metoda otomasi atau
manual digunakan untuk menentukan pembekuan
karena kehilangan serat dializer selama tiap kali HD
(dibandingkan sebelum dan sesudahnya)
• Dializer dapat digunakan lagi jika kehilangan serabut
< 1%.
KASKADE KOAGULASI
 Pengunaan Antikoagulan Selama Dialisis
• Saat antikoagulan (-), pembekuan darah selama 3-4 jam
dialisis  sangat bermakna (5-10%)
• Jika koagulasi terjadi akan menghasilkan:
- Hilangnya dializer dan blood tubing
- Hilangnya 100-150 mL darah
• Kondisi pasien yang berisiko moderat – tinggi untuk
timbulnya perdarahan peri-HD → anticoagulant-free
dialysis
• Dapat diberikan beberapa jenis antikoagulan.
• Di USA paling sering digunakan UFH (Heparin)
sedangkan di Eropa lebih sering LMWH.
 Jenis Antikoagulan
UFH (Heparin )
1. UFH (Heparin )
1. Routine heparin
2. Pada passien dengan resiko perdarahan
• Tight heparin / Minimal Heparin
• Free heparin
2. LMWH
3. Heparinoids (danaparoid and fondaparinux)
4. Regional (high-concentration) citrate
anticoagulation
5. Argatroban
 Jenis Antikoagulan
UFH (Heparin )

Cara kerja :
1. Mengubah ikatan dengan Antitrombin inaktivasi
cepat faktor pembekuan (faktor Xa)
2. Menstimulasi agregasi dan aktivasi Trombosit ><
mengikat dan mengaktivasi faktor koagulasi pada
membran Trombosit
3. Efek yang tak inginkan : pruritus, alergi, osteoporosis,
dyslipidemia, trombositopenia, perdarahan berlebihan
 Tes Hemostasis untuk Monitor
Heparinisasi

• aPTT (activated Partial Thromboplastin Time),

untuk monitor UFH
• WBPTT (Whole Blood Partial Tromboplastin
Time), untuk monitor UFH
• aCT (activated Clothing Time), monitor UFH
• LWCT (Lee-White Clotting Time), jarang digunakan
• Factor Xa-activated ACT, lebih sensitif untuk
monitoring antikoagulan LMWH
UFH (Heparin )
Target CT
 UFH (Heparin )
“Routine heparin prescriptions

There are two basic techniques of

administering routine heparin.
1. A heparin bolus is followed by a constant
heparin infusion.
2. A heparin bolus is followed by repeated
bolus doses as necessary.
 Techniques Of Administering
Routine Heparin.
• Rx: Routine heparin, constant-infusion method.
– Administer the initial bolus dose (e.g., 2,000 units).
The initial heparin dose is best administered to the
patient via the venous access tubing and flushed in
with saline. Wait 3-5 minutes to allow heparin
dispersion before initiating dialysis.
– Start heparin infusion into the arterial blood line (e.g.,
at a rate of 1,200 u/hour (Daugirdas) / 1.000 u/hour
(Konsensus dialis PERNEFRI 2003).
 Techniques of administering
routine heparin.

• Rx: Routine heparin, single-dose-only or repeated-

bolus method.
– Administer the initial bolus dose (e.g., 4,000
units)  (Daugirdas) / 3.000-4.000 u (50-
1000unit/kgbb)  (Konsensus dialis
PERNEFRI 2003).
– Then give an additional 1,000- to 2,000-unit
bolus dose if necessary.
 Techniques of administering
routine heparin.

• Some centers give only a single initial dose (e.g.,

2,000 units) of heparin, with no subsequent
infusion or boluses.
• Some centers give a fairly large (75-100 units/kg)
initial bolus dose followed by a 500- to 750-unit-per-
hour infusion. At this point in time, there has been
little research to convincingly demonstrate an
optimal method of heparin dosing.
 An Optimal Method Of Heparin Dosing.
• Effect of body weight on the size of the heparin dose.
– a population pharmacokinetic study the volume of distribution
of heparin has been found to increase as body weight rise.
• When to terminate the heparin infusion
– T1/2 heparin in dialysis patients averages 50 minutes, (30
minutes - 2 hours).
– For a patient with an average t1/2 heparin 1 hour, if the
heparin infusion during dialysis is prolonging WBPTT or ACT
to the required baseline-plus-80% value, stopping heparin
infusion approximately 1 hour prior to the end of dialysis
– Venous catheters, heparin infusions are commonly continued
right up to the end of dialysis.
 UFH (Heparin )
“Tight heparin”

• Direkomendasikan untuk pasien :

- Risiko perdarahan sedang
- Penggunaan heparin-free dialysis tidak berhasil
karena
• When using WBPTT or ACT to monitor
therapy, the target clotting time is equal to
the baseline value plus 40%. If the baseline
WBPTT or ACT value is >140% of the average
baseline value for patients in the dialysis unit,
it is best not to use heparin and to proceed
with a heparin-free or regional citrate
technique.
 The Tight Heparin Prescription

• A bolus dose followed by a constant infusion of heparin

 the best technique for administering a tight heparin
prescription, because constant infusion avoids the rising
and falling clotting times that are inevitable with repeated-
bolus therapy.
 The Tight Heparin Prescription
• Rx: Tight heparin, constant-infusion method
– Obtain baseline clotting time (WBPTT or ACT).
– Initial bolus dose = 750 units.
– Recheck WBPTT or ACT after 3 minutes.
– Administer a supplemental bolus dose if needed to prolong
WBPTT or ACT to a value of baseline plus 40%.
– Start dialysis and heparin infusion at a rate of 600 units per
hour.
– Monitor clotting times every 30 minutes.
– Adjust the heparin infusion rate to keep WBPTT or ACT at
baseline plus 40%.
– Continue heparin infusion until the end of the dialysis session.
 Heparin-associated Complications

• Increase in blood lipids

– activates lipoprotein lipase  ↑ Trigliserida, ↓HDL.
• Thrombocytopenia
• The potential for hypoaldosteronism and exacerbation
of hyperkalemia
• Pruritus  Allaergic Reaction
• Anaphylactoid reactions
• Osteoporosis
 Heparin-free Dialysis

• Metoda yang dipilih pada pasien dengan perdarahan

aktif, atau dengan risiko perdarahan sedang-tinggi
• Sederhana dan aman  sering digunakan di ICU/ICCU
 Indications For Heparin-free
Dialysis
• Pericarditis
Recent surgery, with bleeding complications or risk,
especially:
Vascular and cardiac surgery
Eye surgery (retinal and cataract)
Renal transplant
Brain surgery
Coagulopathy
Thrombocytopenia
Intracerebral hemorrhage
Active bleeding
Routine use for dialysis of acutely ill patients by many
centers
 The Heparin-free Prescription
• Heparin rinse
– Rinse extracorporeal circuit with saline containing 3,000 units
 heparin can coat extracorporeal surfaces and the dialyzer
membrane to mitigate the thrombogenic response
• High blood flow rate
– Set the blood flow rate to 400 mL per minute if tolerated
• Periodic saline rinse
– Rinse the dialyzer rapidly with 250 mL of saline while
occluding the blood inlet line every 15 minutes.
– Bilas dengan 25-200 cc NaCl 0,9% (Konsensus dialis
PERNEFRI 2003).
 Bicarbonate dialysis solution with
low-concentration citrate (Citrasate)
• When the acid and base concentrates are mixed,
the resulting dialysis solution commonly contains
0.8 mmol/L (2.4 mEq/L) citrate. This small
amount of citrate, by complexing with calcium, 
inhibit blood coagulation and platelet activation
locally at the dialyzer membrane surface 
improved dialyzer clearance and increased
dialyzer reusability .
Other Anticoagulation Techniques
“LMWH”
• LMWH fractions (4,000-6,000 daltons) are
obtained by chemical degradation or sieving of
crude heparin (2,000-25,000 daltons).
• LMWH inhibits factor Xa, factor XIIa, and
kallikrein, but causes so little inhibition of
thrombin and factors IX and XI that partial
thromboplastin time and thrombin time are only
raised by 35% during the first hour and
minimally prolonged thereafter, thus
decreasing bleeding risk.
• The dose of LMWH is generally expressed in anti-
factor Xa Institute Choay units (aXaICU). For a 4-
hour dialysis treatment, a single loading dose of
10,000 or 15,000 aXaICU (125-250 aXaICU/kg) 
successful in providing adequate anticoagulation ,
with little or no prolongation of APTT.
• Hemodialysis using LMWH as the sole anticoagulant 
safe and effective.
• The lower dosage, 125 aXaICU/kg, should be used in
patients who have a mildly increased risk of
hemorrhage.
• Recent animal data revealed that  RLMWH does not
inhibit osteoblast proliferation in vitro educe the risk of
heparin-induced osteoporosis associated with long-term
heparin administration
• Enoxaparin :
– Dosis 0,5-1 mg/kgBB disuntikan ke dalam AVL
pada awal dialisis  Akan cukup selama 4 jam.
– Bila tampak cincin fibrin  Tambahkan
suntikan 0,5-1 mg/kgBB.
• Nadroparin Kalsium
– BB < 50  0,3ml
– BB 50-69  0,4 ml
– BB > 70  0,5 ml.
 Heparinoids (danaparoid and
fondaparinux)
• Danaparoid is a mixture of 84% heparin, 12% dermatan, and
4% chondroitin sulfates. Danaparoid affects predominantly
factor Xa and therefore has to be monitored with anti-Xa
assays. The half-life is prolonged in renal failure, such that
monitoring is sometimes used to check anti-Xa activity prior to
the succeeding dialysis session. In patients >55 kg, a 750-IU
loading dose is recommended, and subsequent doses are
titrated to achieve an anti-Xa activity of 0.25-0.35.
• Danaparoid may cross-react with HIT antibodies in up to 10%
of cases.
• More recently a series of pentasaccharides, such as
fondaparinux, have been developed, which do not cross-react
with HIT antibodies.
 Regional (high-concentration)
citrate anticoagulation
• An alternative to heparin-free dialysis is to
anticoagulate the blood in the extracorporeal circuit
by lowering its ionized calcium concentration
(calcium is required for the coagulation process).
• The extracorporeal blood-ionized calcium level is
lowered by infusing trisodium citrate (which
complexes calcium) into the arterial blood line and
by using a dialysis solution containing no calcium.
• The advantages of regional citrate anticoagulation over heparin-
free dialysis are
– The blood flow rate does not have to be high
– Clotting rarely occurs.
• The principal disadvantages are the requirement for monitoring
the plasma ionized calcium level.
• Because sodium citrate metabolism generates bicarbonate, use of
this method results in a greater than usual increment in the
plasma bicarbonate value.
• Hence, regional citrate anticoagulation should be used with
caution in patients who are at risk for alkalemia.
• When citrate anticoagulation is to be used on a long-term
basis, the dialysis solution bicarbonate level should be
reduced (e.g., to 25 mM) if metabolic alkalosis is to be
avoided. Chronic citrate use may result in aluminum
overload (aluminum contamination from glass container
or from elsewhere).
• This technique is not widely used for intermittent
hemodialysis but is more popular for the continuous
forms of dialysis therapy. A theoretical advantage is the
prevention of platelet activation/degranulation when using
citrate anticoagulation.
 Thrombin Inhibitors
• Argatroban  a synthetic peptide derived from
arginine, acts as a direct thrombin inhibitor. It is
primarily metabolized in the liver.
• Argatroban is licensed for treating patients with HIT.
• A typical loading dose for hemodialysis is 250 mcg/kg,
followed by an infusion of 0.5- 2.0 mcg/kg per minute,
titrated to achieve an APTT of 1.5-2 times the normal
ratio.
• A related drug, melagatran, has been used for
anticoagulation when added to the dialysate, but this
treatment remains experimental at this time
TERIMA KASIH