1. Consultant nephrologist Shirbin General Hospital
Anticoagulation in HD
Faisal Zidan
Consultant nephrologist
Shirbin General Hospital

2. History of Anticoagulation
Abel 1914 : First efficient dialysis system in animal consist of collodion tubes and hirudin solution used as anticoagulant. 
Hess and McGuigan 1914 : clotting is avoided by high blood flows or anticoagulation.
Haas 1924 : first human hemodialysis in Germany using a tubular device made of collodion and hirudin for anticoagulation.
1930s : Unfractionated heparins.
1940s : Vitamin K antagonists.

3. History of Anticoagulation
1980s : LMWH.
1990s : Direct factor IIa inhibitors (Parentral).
2000s : Indirect factor Xa inhibitors (Parentral).
Direct factor IIa inhibitors (Oral).
2008 : Direct factor Xa inhibitors (Oral).

4. Coagulation factors

5. Pumb UF

6. Types of anticoagulants
UFH
LMWH
Regional citrate
Heparinoids
Direct thrombin inhibitors
Platelet inhibiting agents

7. UFH Glycosaminoglycan extracted from bovine or porcine tissues
Half-life 30–120min.
Monitoring :
ACT : (200–250s) during dialysis
(150–200s) during last 60 min. of dialysis
APTT : (target 120–160s).
Binds antithrombin III to inactivate factors II, IX, X, XI, and XII.

8. Mechanism of action of UFH

9. UFH

10. Heparin administration
(There are no good evidence demonstrating the best method)
Infusion method : Initial bolus usually 2000U.
Continuous infusion 500–2000U/h.
Adjust infusion rate to clotting time.
Stop heparin 1h. before end of dialysis.
Bolus method: Initial bolus 1000–4000U.
Repeat ACT in 30min & give other bolus
accordingly.
Stop heparin 1h. before the end of dialysis.
Tight (or minimal) heparin : Initial bolus (750 U) followed by 500 U bolus every 30 min. or 250 : 500 U/h. by infusion & continue till the end of HD.

11. Side efects include:
Major complication is bleeding (in up to 50% of high risk patients).
Heparin-induced thrombocytopenia (HIT)
Pruritus
Thrombocytopenia (rare in HD)
Hyperlipidaemia (mainly hypertriglyceridaemia)
Osteoporosis
Hair loss
Allergy (rare).

12. Enoxaparin, Nadroparin, Tinzaparin, Deltaparin & Reviparin
LMWH
Enoxaparin, Nadroparin, Tinzaparin, Deltaparin & Reviparin
Obtained by fractionation of heparin.
Binds anti-thrombin III and inhibits factor Xa.
Monitored by the anti-factor Xa activity in plasma.
Cleared by renal/dialysis mechanisms, so dosage must be adjusted .
Given as single dose ( may be repeated).

14. LMWH

15. Doses of LMWH in IHD

18. Plt. & Leucocytes activation
UFH vs LMWH
LMWH
UFH
2000 : 9000 Da.
5000 : Da. MW
More rapid
Slower
Onset of action
Long
Short
Duration of action
More
Less
Bioavailability
Anti- Xa level
ACT & APTT
Monitoring
Not needed
Needed
Frequent monitoring No
Protamine
Antidot
Convenience
Nursing demand
HIT
Plt. & Leucocytes activation
Osteoporosis
Alopecia
Dyslipidemia
K & Aldosterone
Expensive
Cheep
Cost

19. UFH vs LMWH

20. No significant differance

21. No significant differance

22. Heparin-coated dialyzer

23. Heparin-free dialysis
Indications:
Actively bleeding patients.
Pericarditis.
Coagulopathy.
Thrombocytopenia.
Intracerebral haemorrhage.
Recent surgery.
Recent renal transplant.

24. Heparin-free dialysis
Common protocol
Rinse circuit with heparinized saline (2000–5000U/L saline).
Use high blood flows (>400mL/min).
Rinse circuit every 15–30min with 25–200mL saline.
Increase UF rate to remove extra saline.
Careful inspection of dialyser.
Monitoring of venous pressure for early signs of clotting.
Avoid blood transfusion.
Use predilution CRRT.
Requires more intensive nursing.
Only 5% risk of complete circuit clotting.

25. Regional anticoagulation
Regional heparin with protamine reversal
Heparin is infused constantly into the dialyzer inlet & protamine is infused into the venous line.
Protamine binds heparin and prevents its anticoagulant activity.
ACT is maintained in the circuit at 200–250s, and also monitored in the blood returning to the patient (should be back to baseline).
1mg protamine reverses 100U of heparin.
This is difficult to monitor.
Rebound bleeding can occur after 2–4h (Can be severe).
Protamine can cause flushing, hypotension and bradycardia.
Rarely used now

26. Heparin regional anticoagulation

27. Regional anticoagulation
Regional citrate anticoagulation
Baseline ACT is measured and then every 30 min. (100% above baseline or 200s)
Trisodium citrate solution (132mmol/L) is infused into the arterial line at 270mL/h
Start blood flow
Start calcium chloride infusion into venous line at 30mL/h
Titrate calcium infusion to plasma calcium level
Ensure neither citrate nor calcium pumps stop working during the procedure
Stop both calcium and citrate infusions at the end of dialysis.
Hypocalcaemia, hypercalcaemia, hypernatraemia and metabolic alkalosis are possible complication.
Where routinely used it is a reliable and effective means of anticoagulation

28. Regional citrate anticoagulation

29. Citrat

30. 1051 session : 3 clottings

35. Decreased KT/V
Hypocalcaemia

36. Danaparoid & Fondaparinux
Heparinoids
Danaparoid & Fondaparinux
Mixture of heparin, dermatan & chondroitin sulphates
Affects predominantly Factor Xa.
Monitored with anti-Xa assay.
Prolonged half-life in ESRD.
Danaparoid cross react with HIT antibodies (10%). But, fondaparinux does not.
Very expensive.
Used only in ttt of HIT

37. Hirudin, Argatroban & Melagatran
Thrombin inhibitors
Hirudin, Argatroban & Melagatran
Synthetic peptide derived from arginine.
Metabolized in the liver.
Direct thrombin inhibitors.
Monitored by APTT.
Huridin is no longer used.
Argatroban is licensed for ttt of HIT.
Very expensive.

38. Recombinant hirudin (lepirudin)
Derived from leeches.
Forms complex with thrombin and inhibits platelet aggregation.
Administered as a single bolus at the start of dialysis (0.08–0.15mg/kg).
Efective but expensive, and has a prolonged half-life (bleeding after repeated use).
Monitored by APTT (aiming 1.5–2.5).
Used only in ttt of HIT

39. Platelet inhibiting agents
Epoprostenol & Nafamostat
Induces inhibition of platelet aggregation and vasodilatation.
Causes more clotting than full heparinization.
Hypotension, headache, flushing, nausea, vomiting, and chest and abdominal pain are possible side effects.
Very expensive.

41. Catheter Lock

42. Catheter Lock

43. Anticoagulants Which one to use ?
IHD
CRRT
High risk of bleeding
HIT

44. IHD
For patients without an increased bleeding risk or impaired coagulation and not already receiving effective systemic anticoagulation, we suggest:
: for anticoagulation in intermittent RRT, we recommend using either unfractionated or low-molecular-wieght heparin rather than other anticoagulations.(1C)

45. CRRT
: for anticoagulation in CRRT, we sugest using regional citrate anticoagulation rather than heparin in patient who do not have contraindications for citrate .(2B)
: for anticoagulation during CRRT, in patient who have contraindications for citrate, we sugest using either unfractionated or low-molecular-weight heparin rather than other anticoagulations.(2C)

46. High risk of bleeding
5.3.3:For patients with an increased bleeding risk who are not receivig anticoagulations, we suggest the following anticoagulation during RRT:
:we sugest using regional citrate anticoagulation rather than no anticoagulation, in patient without contraindications for citrate .(2C)
:we sugest avoiding regional heparinization during CRRT in patient with increased risk of bleeding.(2C)

47. HIT

48. ( Non heparin anticoagulation )
HIT
Treatment:
( Non heparin anticoagulation )
Regional citrate anticoagulation.
Heparin free dialysis.
Other alternatives:
Heparinoids ( fondaparinux )
Direct anti-thrombin inhibitors

49. Problem solving Frequent clotting Clotting during dialysis
• blood becomes very dark in circuit
• streaking in dialyser
• visible clots in bubble trap
• visible clots in venous lines
• clots in arterial end of dialyser (not just small strands)
• venous pressure will drop if clot forming in dialyser, or rise if clot distal to monitor
• arterial pressure may rise.

50. Problem solving Frequent clotting Review priming: Heparin Air
Re-evaluat vascular access:
Inadequate flow
Interrupted flow
Re-evaluat heparinization:
Small dose
Delayed starting
Failure of heparin pump

51. Problem solving Frequent bleeding Evaluate vascular access
Evaluate needle insertion technique
Evaluate heparin dose

52. Thank you