Low molecular weight heparin Benefits Drawbacks ❖ Easier to dose: single predialysis ❖ Cost dose may be sufficient ❖ Prolonged half-life ❖ More predictable kinetics ❖ More reliable anticoagulant ❖ Risk of accumulation in kidney failure response ❖ Reduced risk of HIT ❖ Monitoring requires nonroutine test ❖ Less hypertriglyceridemia (anti–Factor Xa) ❖ Incomplete reversal by protamine Shen JI, et al. Am J Kidney Dis. 2012;60(3):473-486. KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012
Content ❖ Standard anticoagulant treatment: Heparin ❖ Standard anticoagulant treatment: Low molecular weight heparin ❖ Prevent clotting during hemodialysis in HIT ❖ Prevent circuit clotting in high risk of bleeding
Adverse effects: LMWH vs. Heparin ❖ Hyperlipidemia ❖ Osteoporosis ❖ Hyperkalemia ❖ Thrombocytopenia Heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia in hemodialysis ❖ Type I HIT ❖ Heparin binds, activates, and depletes platelets ❖ Non-immune platelet aggregation ❖ Typically occurs within the first 4 days of starting heparin therapy ❖ Mild thrombocytopenia with average 100,000/mm3 ❖ Resolves with time ❖ Heparin therapy does not need to be stopped Syed S, Nat Rev Nephrol 2009;5:501-11.
Heparin-induced thrombocytopenia in hemodialysis
Heparin-induced thrombocytopenia in hemodialysis ❖ Type II HIT ❖ Usually occurs 5-12 day ❖ Heparin binds to platelets, releasing platelet factor 4 (PF4) ❖ PF4/heparin antibodies ❖ More platelet aggregation ❖ Paradoxical thrombus formation with limb-threatening ischemia Syed S, Nat Rev Nephrol 2009;5:501-11. Shen JI, et al. Am J Kidney Dis. 2012;60(3):473-486 .
Heparin-induced thrombocytopenia in hemodialysis ❖ Frequency of HIT ❖ 8.1% vs 1.8% of patients exposed to heparin and LMWH ❖ Extensive cross-reactivity (>90 percent) between the LMWH and standard heparin in terms of antibody recognition ❖ Incidence of heparin-induced antibodies by immunoassay was highest during the first 90 days of hemodialysis (20 %) Syed S, Nat Rev Nephrol 2009;5:501-11. Asmis LM, et al. Thromb Haemost 2008; 100:498.
Lo GK, Juhl D, Warkentin TE, et al. J Thromb Haemost 2006; 4:759.
Lo GK, Juhl D, Warkentin TE, et al. J Thromb Haemost 2006; 4:759.
Lo GK, Juhl D, Warkentin TE, et al. J Thromb Haemost 2006; 4:759.
Heparin-induced thrombocytopenia in hemodialysis ❖ All heparin must be stopped ❖ Using direct thrombin inhibitors (argatroban) or Factor Xa inhibitors (danaparoid or fondaparinux) > other or no anticoagulation during RRT (1A) ❖ In a patient with HIT who does not have severe liver failure ❖ Using argatroban rather than other thrombin or Factor Xa inhibitors during RRT (2C) KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012
Argatroban, administered by each treatment regimen, provides safe, adequate anticoaHgeumlaotidoinaltyoseisneafbfliecascuycwceitshsafurgl ahtermoboadniaalnytsicisoainguElSaRtiDonpatients Murray PT, et al. Kidney International, 2004: 66: 2446–2453
New anticoagulant in dialysis Direct thrombin inhibitors Heparinoids Argatroban or bivalirudin Danaparoid or fondaparinux Prolonged half-life Prolonged half-life Cost Cost No reversal agent No reversal agent Used in patients with history of HIT Used in patients with history of HIT No safe in hepatic impairment Shen JI, et al. Am J Kidney Dis. 2012; 60(3):473-486
Anticoagulants used to treat patients with HIT John Feehally, et al. Comprehensive Clinical Nephrology 2019 6th edition
Kessler M et al. Seminars in Dialysis. 2015: 28: 474-89.
Content ❖ Standard anticoagulant treatment: Heparin ❖ Standard anticoagulant treatment: Low molecular weight heparin ❖ Prevent clotting during hemodialysis in HIT ❖ Prevent circuit clotting in high risk of bleeding
Setting: avoid anticoagulant treatment Active bleeding Pericarditis Recent surgery, with bleeding complications or risk Coagulopathy Thrombocytopenia Intracerebral hemorrhage Routine use for dialysis of acutely ill patients by many centers บัญชา สถิระพจน์, Manual of Dialysis. กรุงเทพ: นำอักษรการพิมพ์; 2561.
Normal saline flushing ❖ No heparin hemodialysis for high risk of bleeding ❖ Pretreating with 2000-5000 U of heparin with 0.9%NaCL 1 L ❖ BFR 250 to 500 mL/min ❖ Saline flushes 100-200 mL q 15-30 min into the arterial limb ❖ Minimize hemoconcentration and fibrin strands ❖ Careful monitoring of the arterial and venous pressure alarms and saline volume
239 hemodialysis treatments (91 percent) were successfully completed. Solute clearance, and ultrafiltration rate, were not different from those in patients who underwent hemodialysis with anticoagulation.
Normal saline flushing Labor (frequent monitoring and flushing of the extracorporeal circuit) Risk for air embolism Low efficiency
Normal saline Flushing Benefits Drawbacks ❖ Can be used in patients with ❖ Cost (due to increased changing of history of HIT dialyzer) ❖ Lowest risk of bleeding ❖ Labor (frequent monitoring and flushing of the extracorporeal circuit) ❖ Difficulty achieving goal ultrafiltration ❖ Risk for air embolism Shen JI, et al. Am J Kidney Dis. 2012;60(3):473-486. ❖ Low efficiency KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012
Regional citrate anticoagulation ❖ Reduced incidence of bleeding compared to standard heparin protocols ❖ Trisodium citrate solution into the arterial side of the dialyzer ❖ Fall free plasma calcium induced by binding to citrate for the anticoagulant activity ❖ Citrate-calcium complex is removed across the dialyzer ❖ Reversed by 5% CaCl2 infuse into the venous return at a rate of 0.5 mL/ min Janssen MJ, et al Nephrol Dial Transplant. 1993;8(11):1228.
Regional citrate anticoagulation
Comparison of regional citrate anticoagulation protocols John Feehally, et al. Comprehensive Clinical Nephrology 2019 6th edition
Citrate for long-term hemodialysis: prospective study of 1,009 consecutive high-flux treatments in 59 patients Clotting Scores During Citrate-Anticoagulated High-Flux Hemodialysis Treatments Of the treatments, 99.6% were accomplished successfully. Routine use of citrate anticoagulation in the setting of a long-term hemodialysis ward is safe and efficient Apsner R, et al. Am J Kidney Dis. 2005;45(3):557.
Regional citrate anticoagulation Benefits Drawbacks ❖ Can be used in patients with history ❖ Risk of accidental overdose with of HITa potentially fatal consequences ❖ Low risk of bleeding ❖ Other metabolic complications (acidosis, alkalosis, hypernatremia, Shen JI, et al. Am J Kidney Dis. 2012;60(3):473-486. hypocalcemia, hypercalcemia) KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012 ❖ Increased complexity and frequent monitoring ❖ Insufficient citrate metabolism in patients with reduced liver function and shock
Citrate dialysate ❖ Prospective, randomized, crossover study of 74 dialyses ❖ Citric acid-based dialysates reduced clotting in no-heparin dialysis by lowering serum calcium enough to interfere with the clotting cascade Ahmad S, et al. Am J Kidney Dis. 2000; 35(3):493.
Citric acid dialysate was well tolerated, and increases the delivered dialysis Ahmad S, et al. Am J Kidney Dis. 2000; 35(3):493.
Kessler M et al. Seminars in Dialysis. 2015: 28: 474-89.
Recommendations: Anti-coagulation in AKI Impaired coagulation ? Yes Proceed without anticoagulation Underlying condition requires Systemic anticoagulation? Yes Use anticoagulation adapted to this condition Choose RRT Modality CRRT Intermittent RRT Contraindication No Regional Citrate Increased Bleeding No to Citrate? Anticoagulation Risk? Heparin Increased Bleeding Heparin Yes Risk? No Proceed without Proceed without anticoagulation anticoagulation KDIGO Clinical Practice Guideline for Acute Kidney Injury 2012
Content ❖ Standard anticoagulant treatment: Heparin ❖ Standard anticoagulant treatment: Low molecular weight heparin ❖ Prevent clotting during hemodialysis in HIT ❖ Prevent circuit clotting in high risk of bleeding
Dialysis-specific factors: clotting Low blood flow High hematocrit High ultrafiltration rate High dialyzer surface area Dialysis access recirculation Intradialytic blood and blood product transfusion Intradialytic lipid infusion Use of drip chambers (air exposure, foam formation, turbulence) บัญชา สถิระพจน์, Manual of Dialysis. กรุงเทพ: นำอักษรการพิมพ์; 2561.
Thank you for your attention Intelligence Dialysis Center Nephrology Unit Phramongkutklao Hospital and College of Medicine
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