NDT Advance Access originally published online on July 5, 2006
Nephrology Dialysis Transplantation 2006 21(11):3341-3342; doi:10.1093/ndt/gfl352
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The use of lepirudin in haemodialysis complicated with heparin-induced thrombocytopenia type II (HIT II)—dosage monitoring
Email: tkassimatis{at}yahoo.grSir,
Heparin-induced thrombocytopenia type II (HIT II) is an unpredictable prothrombotic, immune-mediated life-threatening complication that occurs following administration of unfractionated heparin (UFH) or low-molecular weight heparin (LMWH) for a variety of prophylactic or therapeutic applications [1]. The mainstay of HIT treatment consists of the immediate cessation of all forms of heparin therapies and the simultaneous initiation of non-heparin, rapidly acting anticoagulant therapies with direct thrombin inhibitors (DTIs) [1]. DTIs bind directly to thrombin, thus preventing fibrin formation and clotting. The three available DTIs are lepirudin, argatroban and bivalirudin, with only lepirudin and argatroban being currently approved by the U.S. Food and Drug Administration for use in HIT [1].
The major challenges of lepirudin treatment, given by any route, are the lack of an antidote and the extreme care needed when treating patients with any degree of renal insufficiency as it is primarily eliminated through the kidneys. Therefore, dosing must be reduced in patients with impaired renal function [1]. Moreover, its use is currently not indicated in patients requiring haemodialysis [2]. Only anecdotal reports are available on the usage of lepirudin as anticoagulant in haemodialysis [3–5].
Adding one more anecdotal case, we report a 23-year-old female who developed HIT following pre-emptive, living related donor, renal transplantation. The patient was pre-operatively exposed to both UFH and LMWH heparin during five haemodialysis sessions. HIT (diagnosed on the basis of both clinical and serological grounds) caused right common and external iliac vein and renal graft artery and vein thrombosis, resulting in graft loss. Heparin-free haemodialysis was continued using the DTI lepirudin as anticoagulant for both thromboses and haemodialysis. The dose of lepirudin (given as repetitive intravenous boli) was titrated based on the activated partial thromboplastin time (aPTT) in order to maintain an aPTT value of 70–80s [1]. In detail, the patient received 0.005 mg/kg/h of lepirudin the first day, 0.0024 mg/kg/h the second day, 0.0016 mg/kg/h the third day and for the subsequent 7 days 0.0012 mg/kg/h as a maintenance dose. She was then switched to oral anticoagulation treatment with acenocoumarol after a combined anticoagulation period of 5 days. aPTT values were evaluated every 3 h in the first day and every 4 h thereafter. The patient underwent four haemodialysis sessions post-operatively without any bleeding complications. Finally, she was accepted into the continuous ambulatory peritoneal dialysis (CAPD) programme.
It should be noted that although lepirudin dose for normal renal function is 0.15 mg/kg/h and for patients with creatinine clearance of 15–29 ml/min is reduced to 0.0225 mg/kg/h, the appropriate dose for patients requiring haemodialysis is almost 125 and 19 times less, respectively, suggesting that extremely cautious dosing adjustments at shorter intervals (i.e. every 4 h) should be made in such cases.
Recently, Haase et al. [6] successfully used fondaparinux as an anticoagulant in a dialysis patient with symptomatic HIT II. The pentasaccharides seem to have a promising role in treatment and/or prevention of HIT, since they do not appear to interact with platelets or platelet factor 4. However, fondaparinux, as lepirudin, is eliminated primarily through the kidneys (it is contraindicated in patients with creatinine clearance <30 ml/min), thus leaving the issue of appropriate dosing in dialysis patients in pendency.
We conclude that lepirudin can be used with safety in patients requiring short-term haemodialysis, providing aPTT is closely monitored, especially on the first day of treatment.
Conflict of interest statement. None declared.
1Nephrology Department
2Hematology Laboratory
"Evangelismos" General Hospital
Athens
Greece
References
- Greinacher A and Warkentin TE. (2006) Recognition, treatment, and prevention of heparin induced thrombocytopenia: review and update. Thromb Res 118:165–176.[CrossRef][Web of Science][Medline]
- Refludan® [package insert] (2002) Wayne, NJ: Berlex Laboratories.
- Dager WE and White RH. (2001) Use of lepirudin in patients with heparin-induced thrombocytopenia and renal failure requiring hemodialysis. Ann Pharmacother 35:885–890.[Abstract]
- Fischer KG, van de Loo A, Bohler J. (1999) Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis. Kidney Int Suppl 72:S46–S50.[Medline]
- Chuang P, Parikh C, Reilly RF. (2001) A case review: anticoagulation in hemodialysis patients with heparin-induced thrombocytopenia. Am J Nephrol 21:226–231.[CrossRef][Web of Science][Medline]
- Haase M, Bellomo R, Rocktaeschel J, et al. (2005) Use of fondaparinux (ARIXTRA) in a dialysis patient with symptomatic heparin-induced thrombocytopaenia type II. Nephrol Dial Transplant 20:444–446.
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