A 55 year old with severe sepsis develops Heparin Induced Thrombotic Thrombocytopenia Syndrome (HITTS) while on continuous veno-venous haemodiafiltration (CVVHDF).
Outline the strategies available for prolonging the life of the CVVHDF circuit in this patient, mentioning the advantages and disadvantages of each strategy.
No Anticoagulant +/- Saline Flushes (50-100ml every hour)
* Ensure good wide bore access, high flow rates, consider predilution
Advantage:
Minimizes bleeding risk, but consumption of platelets and factors by membrane
(theoretical)
Disadvantage:
Shortened filter life / increased time off dialysis
Regional citrate
Advantage:
Provides good regional anticoagulation
Pre-mix solutions and protocols for use have simplified process
Disadvantage
Labor intensive,
Requires diligent monitoring of serum sodium, ionized calcium, and bicarbonate
Requires infusion of calcium outside the circuit (access issues) Large sodium load occurs when trisodium citrate used
May cause alkalosis
Special diasylate required: hyponatraemic, without buffer, Ca free
Not appropriate in liver failure
Prostacycline and Analogues
Advantages
Reduced bleeding risk
Disadvantages
Shorter filter life
Hypotension
Direct thrombin Inhibitors: Hirudin / Lepirudin / Argatroban
Advantages:
Linear relationship between levels and APTT (<100s) for Hirudin
Disadvantages
Renal clearance, accumulation in renal failure (Hirudin, Lepirudin) Hepatic metabolism, accumulation in liver disease (Argatroban) No antagonist
Argatroban falsely raises INR / PT Expense
Other agents Danaparoid Limited availability
Risk of cross-reactivity with heparin-induced antibodies
Serine Protease inhibitors (nafamostat)
limited experience, massive cost
Fondaparinux
Not readily available
Limited evidence supporting its use
Warfarin /NSAIDS
Thus question would have benefited from a tabulated answer.
In the table below, I have included heparin, for completeness. However one would be well-advised to omit heparin from their answer in the exam.
If one were to review only one resource for this answer, one would be satisfied by this article from Tolwani and Wille.
Strategy | Advantages | Disadvantages |
Nothing whatsoever (+/- regular saline flushes) |
|
|
High flow rate |
|
|
Filtration fraction under 25% |
|
|
Pre-dilution |
|
|
Unfractionated heparin |
|
|
Regional anticoagulation with heparin and protamine |
|
|
Low molecular weight heparin |
|
|
Warfarin |
|
|
Platelet function inhibitors: NSAIDs, aspirin, etc |
|
|
Citrate |
|
|
Direct thrombin inhibitors: Hirudin / Lepirudin Bivalirudin / Argatroban |
|
|
Heparinoids (Danaparoid) |
|
|
Xa inhibitors: Fondaparinux |
|
|
Serine protease inhibitors: Nafamostat |
|
|
Prostacyclin (PGI2) |
|
|
This table is reproduced with minimal changes in the Required Reading section on this topic.
Lewis, P. J., and C. T. Dollery. "Clinical pharmacology and potential of prostacyclin." British medical bulletin 39.3 (1983): 281-284.
Fiaccadori, Enrico, et al. "Continuous haemofiltration in acute renal failure with prostacyclin as the sole anti-haemostatic agent." Intensive care medicine 28.5 (2002): 586-593.
Han, Sang Jin, et al. "Use of nafamostat mesilate as an anticoagulant during extracorporeal membrane oxygenation." Journal of Korean medical science26.7 (2011): 945-950.
Hu, Z. J., et al. "Time course of activated coagulation time at various sites during continuous haemodiafiltration using nafamostat mesilate." Intensive care medicine 25.5 (1999): 524-527.
Akizawa, T., et al. "Nafamostat mesilate: a regional anticoagulant for hemodialysis in patients at high risk for bleeding." Nephron 64.3 (1993): 376-381.
Wester, J. P., et al. "Low-dose fondaparinux in suspected heparin-induced thrombocytopenia in the critically ill." Neth J Med 65.3 (2007): 101-108.
Mahieu, Elien, et al. "Anticoagulation With Fondaparinux for Hemodiafiltration in Patients With Heparin‐Induced Thrombocytopenia: Dose‐Finding Study and Safety Evaluation." Artificial organs 37.5 (2013): 482-487.
Morabito, Santo, et al. "Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding." Journal of nephrology16.4 (2003): 566-571.
Tan, H. K., I. Baldwin, and R. Bellomo. "Continuous veno-venous hemofiltration without anticoagulation in high-risk patients." Intensive care medicine 26.11 (2000): 1652-1657.
Tolwani, Ashita J., and Keith M. Wille. "THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Anticoagulation for Continuous Renal Replacement Therapy." Seminars in dialysis. Vol. 22. No. 2. Blackwell Publishing Ltd, 2009.
Davies, H. T., et al. "A randomized comparative crossover study to assess the affect on circuit life of varying pre-dilution volume associated with CVVH and CVVHDF." The International journal of artificial organs 31.3 (2008): 221-227.
Davenport, Andrew. "Pre-dilution or post-dilution fluid replacement for continuous veno-venous hemofiltration: that is the question." Nephron Clinical Practice 94.4 (2004): c83-c84.
Davies, Hugh, and Gavin Leslie. "Maintaining the CRRT circuit: non-anticoagulant alternatives." Australian Critical Care 19.4 (2006): 133-138.
Reeves, John H., et al. "A controlled trial of low-molecular-weight heparin (dalteparin) versus unfractionated heparin as anticoagulant during continuous venovenous hemodialysis with filtration." Critical care medicine 27.10 (1999): 2224-2228.
Jeffrey, R. F., et al. "Anticoagulation with low molecular weight heparin (Fragmin) during continuous hemodialysis in the intensive care unit." Artificial organs 17.8 (1993): 717-720.
Wilkieson, Trevor J., et al. "Low-intensity adjusted-dose warfarin for the prevention of hemodialysis catheter failure: a randomized, controlled trial."Clinical Journal of the American Society of Nephrology 6.5 (2011): 1018-1024.
Teraoka, Satoshi, et al. "Heparin-free hemodialysis with an oral anti-platelet agent." ASAIO journal 38.3 (1992): M560-M563.
De Pont, Anne-Cornelie JM, et al. "Pharmacokinetics and pharmacodynamics of danaparoid during continuous venovenous hemofiltration: a pilot study."Critical Care 11.5 (2007): R102.
Haase, Michael, et al. "Use of fondaparinux (ARIXTRA®) in a dialysis patient with symptomatic heparin-induced thrombocytopaenia type II." Nephrology Dialysis Transplantation 20.2 (2005): 444-446.
Ho, Grace, et al. "Use of fondaparinux for circuit patency in hemodialysis patients." American Journal of Kidney Diseases 61.3 (2013): 525-526.