NDT Advance Access originally published online on March 29, 2007
Nephrology Dialysis Transplantation 2007 22(6):1790-1791; doi:10.1093/ndt/gfm032
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Long-term application of lepirudin on chronic haemodialysis over 34 months after heparin-induced thrombocytopenia
Email: hansjuerg.beer{at}ksb.chSir,
The development of heparin-induced thrombocytopenia (HIT) is a well-known complication of heparin therapy. Once the syndrome occurs and is recognized, it is essential to immediately avoid any sources of heparin. If anti-coagulation is still required, other anti-coagulants should be considered such as lepirudin, argatroban, danaparoid or fondaparinux in the acute phase usually followed by warfarin after normalization of the thrombocytes.
A 75-year-old hypertensive male Caucasian with pre-endstage renal disease was admitted to this hospital because of acute aortic dissection. The aorta was successfully replaced by a composite graft at the University Hospital of Zürich. Post-operatively, the patient was anuric and continuous venovenous haemofiltration (CVVH) was installed with unfractionated heparin as anti-coagulant. The patient was transferred back to this hospital. HIT II was diagnosed based on a drop of the platelet count from 190 to 44 x 109/µl on day 7 in the absence of alternative explanations and confirmed by ELISA (Asserachrom HPIA, Fa Stago/Roche). CVVH was continued initially without any anti-coagulant (Fresenius Filter F6, no blood dilution, flow 250 ml/min). Haemodialysis was initiated on day 14 post-operatively with a low-flux dialyser (Hemoflow F6, Fresenius Medical Care) using lepirudin to achieve adequate anti-coagulation. Lepirudin is an irreversible thrombin inhibitor whereas heparin binds to anti-thrombin which inactivates thrombin and FXa. We chose lepirudin because of already existing short and intermediate-time experience in haemodialysis-patients [1,2]. Lepirudin was given as an intravenous bolus immediately before dialysis (0.025 mg/kg body weight, total dose: 3.5 mg). The monitoring was performed by the activated partial thromboplastin time (aPTT), in analogy to the HAT-Studies [3] by the thrombin time (TT) (5 NIH-E/ml), by the lepirudin concentration [4], and by the observation of eventual clotting in the venous chamber.
For the first four haemodialysis sessions, we used a low-flux dialyser (Fresenius Hemoflow F6). After the introduction of a high flux filter (CT 190, Baxter) a large clot built up in the venous chamber. We therefore increased the lepirudin dose before the dialysis to 0.07 mg/kg bw (=5 mg), but the clot still formed repeatedly. With a further increase to 7 mg with dose splitting [two-thirds (4.5 mg) at the beginning and one-third (2.5 mg) after 1.5 h of dialysis], the problem was solved. We interpreted this as an increased initial extraction by the high-flux filter which correlates with the findings on membrane permability by other authors [5,6]. For 34 months now, no further changes of the lepirudin dose were required. Anti-lepirudin antibodies were negative 10 months after the introduction of haemodialysis (methods: 6, 7). The use of lepirudin may be associated with the development of anti-hirudin antibodies in 45–74% of the patients [7]. These antibodies may lead to a prolonged functional halflife and to an increased anticoagulatory effect.
Lepirudin is eliminated from the organism exclusively by the kidneys and its plasma levels correlate linearly with the creatinin clearance [4]. At low plasma concentrations, anticoagulation monitoring seems possible with aPTT, but the linear relation is lost at higher concentrations [8]. The ecarin clotting time is proposed for lepirudin monitoring at higher concentrations [4,9].
We conclude that long-term application of lepirudin at split-low dose in HIT-patients on haemodialysis represents an effective and safe alternative.
Conflict of interest statement. None declared.
1Department of Medicine
2Central Laboratory Kantonsspital Baden
5404 Baden
Switzerland
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