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Anticoagulation in hemodialysis
This document provides an overview of anticoagulation options for hemodialysis. It discusses conventional anticoagulants like unfractionated heparin and low molecular weight heparins. It also covers newer direct thrombin inhibitors and regional anticoagulation methods using citrate or prostacyclin. The risks and benefits of each option are evaluated based on bleeding risks, reversibility, cost, and ability to prevent clotting during hemodialysis procedures. Monitoring requirements and dosing protocols are also reviewed for different anticoagulant regimens.
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Anticoagulation in hemodialysis
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- 2. Brief overview ofpresentation Hemostasis & basic coagulation cascade Conventional anticoagulants Newer drugs Evidence based medicine
- 3. Introduction- Hemostasis Hemostasis isdefined as process of platelet – fibrin thrombus formation to seal a site of vascular injury without resulting in total occlusion of the vessel
- 6. On hemodialysis • Allthe part of the extracorporeal circuit are thrombogenic. • Intrinsic coagulation pathway is invariably activated at all times patient is taken on HD. • Without anticoagulation, 4 hrs HD will lead to a) 5-10 % cases to have clotting b) loss of 100-150ml blood loss c) Early loss of the dialyser
- 7. Factors favouring increasedclotting • Low blood flow rates • High UF rate • Intradialytic blood, blood products,albumin and lipid infusion, iv drips – infusions • Dialysis access recirculation • High hematocrit of patient • Retained air in dialyser, inadequate priming
- 8. Signs of clotting •Extremely dark blood in circuit • Black streaks in dialyser- clotted fibres Grade I clotting- < 10 % fibres Grade II clotting- 10- 50 % fibres Grade III clotting- > 50 % fibres • Clots in arterial side header • Foaming and clot in drip chamber and venous trap • Rapid filling of the transducer monitors with blood
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- 11. Monitoring of heparin •aPTT (Kaolin) • WBPTT (Whole Blood PTT - Actin FS reagent) • ACT (Activated clotting time –silica ) • Lee-White Clotting test (Capillary test) • Factor Xa assay • Factor Xa Clotting time
- 12. Heparin (UFH) prescription a)Routine/ Regular heparin • Bolus f/b Continous infusion • Blous f/b Intermittent boluses b) Tight/ low heparin
- 13. Routine heparin A) Bolusf/b constant infusion Bolus - 1000 U from the venous acsess tubing f/b saline flush and wait for 3- 5 min before initiating HD Infusion - 1000 U/hr from the arterial line
- 14. B) Bolus f/bintermittent boluses Bolus - 4000 U from the venous acsess tubing f/b saline flush and wait for 3- 5 min before initiating HD Intermittent boluses - 1000 – 2000 U if necessary from the arterial line
- 15. Tight heparin Bolus -750 U from the venous access tubing f/b saline flush . Check WBPTT/ACT after 3 min • If levels not upto baseline + 40% give more bolus • If yes then start HD Infusion - 600 U/hr from the arterial line Continue till the termination
- 16. Target to achieve-by WBPTT/ACT Regular heparin Tight heparin Predialysis Post dialysis Predialysis Post dialysis Baseline + 80 % Baseline + 40 % Baseline + 40 % Baseline + 40 % WBPTT- 60-80 sec ACT – 120-150 sec
- 17. When to terminatethe heparin Regular with continous infusion or int. bolus 1 hour before termination – AVF/Graft Till the end – Catheter Tight heparin – Till the end
- 18. Normal heparin vslow dose heparin Normal heparin - Infusion rates of 1000 u/hr Low dose heparin - Infusion rates of 500 u/hr
- 19. Heparin associated complications BOAT-PHD • Bleeding • Osteoporosis • Alopecia ,Anaphylaxis • Thrombocytopenia , thrombosis (HITT) • Pruritus • Hyperkalemia • Dyslipidemia (Inc- TG, Dec- HDL)
- 20. No Heparin /Heparin free Dialysis HITT syndrome Pericarditis Acute bleeding disorder Coagulopathy , thrombocytopenia Recent surgery, Head injury Polytrauma
- 21. Heparin free HD Initialrinse – Rinse the extracorporeal circuit with 3000 units UFH in 1 litre saline. Drain- allow the heparinised saline to drain out completely before venous return to patient by filling the circuit with patients blood or normal saline
- 22. Blood flow rates-400ml/min Periodic saline rinse – 250 ml every 15 min • To reduce clot formation ?????? • To inspect if there is ongoing clot formation
- 23. Disadvantages • Partial clotting- 20% of cases • Complete clotting - 7% • Catheter clotting • Inadequate HD • Labour and cost intensive
- 24. Low molecular weightheparin (LMWH) • Superior pharmacokinetics, • Higher bioavailability, • Less non-specific binding (Xa: Antithrombin activity = 3:1, Heparin has 1:1 and added inhib of TFPI) • Hence predictable dosing • Longer half-life
- 25. Other advantages • Lessdyslipidemia • Less pruritus • Less hyperkalemia • Less osteoporosis • Less HITT
- 26. Dose Single loading doseof 125-250 anti factor XA Institute Choay Units (aXa ICU)/kg at the start of hemodialysis . No monitoring needed.
- 27. LMWH Enoxaparin Dalteparin, Nadroparin, Reviparin Tinzaparin More the Anti-Xa/anti-IIaactivity (2-4 ), lesser the effect of protamine has on reversal Enoxaparin High anti-Xa/anti-IIa ratio of 3.8, and is < 60% reversible with protamine
- 28. Is LMWH better? Ameta-analysis including 11 studies published in 2004 - “LMWH and UF heparin were similarly safe and effective in preventing extracorporeal circuit thrombosis, with no significant difference in terms of bleeding, vascular compression time or thrombosis” J. Am. Soc. Nephrol. 2004; 15: 3192–206.
- 29. Is LMWH better? LMWHis however recommended as the agent of choice for routine haemodialysis by the European Best Practice Guidelines “The single factor weighing against the use of LMWH as the routine form of anticoagulation for dialysis is cost” USFDA has still not approved it for HD Nephrology 2010;15:386–392
- 30. Heparinoids - Danaparoid •Extracted from pig gut mucosa • Heparinoid of molecular weight of 5.5 kDa, mixture of 84% heparan sulphate, 12% dermatan sulphate and 4% chondroitin sulphate
- 31. Danaparoid • Binds toantithrombin but minimal impact on platelets and a low affinity for PF4 • More selective for Xa than even the LMWH Xa : thrombin binding Danaparoid- 22–28 : 1 LMWH - 3:1 UFH – 1:1 • Low cross-reactivity with HIT antibodies (6.5–10%) although recommended to test for cross-reactivity before use of Danaparoid in acute HIT Type II
- 32. Dose – Bolus dose-750 IU for wt >55kg Intermittent boluses – to achieve anti – Xa activity of 0.25-0.35 Disadvantage- No reversal agent Long action (30 hrs) 10 % risk of HITT Fondaparinux 7.5 mg s/c can be used - a synthetic pentasaccharide which is safe in HITT (do not cross react with PF4 antibodies)
- 33. Direct thrombin inhibitors-DTI’s HIRUDIN • Originally discovered in the saliva of leeches • Binds thrombin irreversibly at its active site and the fibrin-binding site • Recombinant variants are also available – Lepirudin, – Desirudin and – Bivalirudin
- 34. Argatroban • Synthetic derivativeof L-arginine • Binds irreversibly to the catalytic site • Short half-life of 40–60 min • Not effected by renal function • Hepatic clearance means prolonged duration of action in patients with liver failure • Bolus- 250 mcg/kg f/b 0.5 -2 mcg/kg/min to titrate to level of aPTT 1.5 -2 times normal
- 35. Argatroban • Anticoagulant effectcan be monitored by a variant of the APTT – the ecarin clotting time • No available reversal agent
- 36. Melagatran • Experimental • Availableorally as a prodrug, which is taken twice a day • Renally cleared and has a prolonged half-life • No antidote • Hepatotoxic
- 37. Citrasate / citricondialysate solution • Bicarbonate dialysis solution with low citrate concentration (2.4 meq/l) • Done by adding citric acid instead of acetic acid at a low dose. • Citrate chelates calcium and inhibits coagulation. • As a part of low or heparin free HD
- 38. Regional anticoagulation forHD To restrict the anticoagulant effect to the dialysis circuit and prevent systemic anticoagulation in patients at increased risk of bleeding.
- 39. 1) UF heparin/protamine •Historically, the use of UF heparin/protamine was prototypical of regional anticoagulation • UF heparin is infused into the arterial line and protamine into the venous line • Dose of 1 mg protamine/100 units heparin
- 40. 1) UF heparin/protamine •Procedure can be technically challenging and • No significant advantage over ‘low-dose’ heparin regimens • Reactions to protamine are not uncommon and may be serious • Can’t be used in HITT syndrome
- 41. 2) Citrate regionalanticoagulation • Isoosmotic trisodium citrate infusion is given into the arterial side of the dialysis circuit • It chelates calcium and decreases coagulation in the extracorporeal circuit. • But to avoid patient landing up with hypocalcemia, calcium chloride is infused at the venous end
- 42. Advantages over heparinfree HD • No need of very high blood flow rates • Better outcomes as compared to heparin free method for avoiding clotting
- 43. Disadvantages • Risk ofalkalemia as citrate metabolises to bicarbonate – dialysate bicarb shoud be reduced • Risk of hypernatremia • Need hourly monitoring of ionised calcium, either hyper or hypocalcemia is dangerous • Need two infusions- TSC and CaCl3
- 44. 3) Prostacyclin regionalanticoagulation • Vasodilator and platelet aggregation inhibitor • Very short half-life of 3–5 min • Infused into the arterial line • Side effects Headache, light headedness, facial flushing, hypotension prohibitive cost