Lepirudin in patients with heparin-induced thrombocytopenia – results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3

Abstract

Summary. Objectives: To assess efficacy and safety of lepirudin in patients with heparin‐induced thrombocytopenia (HIT) in a prospective study (HAT‐3) as well as in a combined analysis of all HAT study data. Patients/methods: Patients with laboratory‐confirmed HIT were treated with lepirudin in three different aPTT‐adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic complications (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison. Results: After start of lepirudin in 205 patients treated in HAT‐3, the combined endpoint occurred in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occurred. Major bleeding occurred in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start of lepirudin treatment, the combined endpoint occurred in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with the historical control group (log‐rank test), the combined endpoint after start of treatment was reduced (29.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg−1 h−1. Major bleeding was more frequent in the lepirudin‐treated patients (29.4% vs. 9.1%, P = 0.0148). Conclusions: The rate of new TECs in HIT patients is low after start of lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg−1 h−1.

Pitfalls in the diagnosis of heparin‐Induced thrombocytopenia: A 6‐year experience from a reference laboratory

“…stopped and replaced with an alternative anticoagulant, which may be associated with a higher risk of bleeding and may be difficult to monitor [21,[25][26][27][28][29]. Our data showed that 20.9% of all samples referred for HIT investigation to a reference laboratory were positive in the EIA but negative in the SRA (presumed false-positive HIT test).…”

Fondaparinux treatment in heparin induced thrombocytopenia:a case report

“…Bazal PTT'nin 1.5-2.5 katı olacak şekilde lepirudin doze edilmeli ve dört saat aralıklarla PTT takibi yapılmalı-dır (8). Lepirudinin kullanımını sınırlayan en önemli yan etkisi %15.4 oranında görülen kanama komplikasyonudur (30). Özellikle kanama komplikasyonu %1.2-3.9 oranlarında ölümcül olabilmektedir (30,31).…”

“…Lepirudinin kullanımını sınırlayan en önemli yan etkisi %15.4 oranında görülen kanama komplikasyonudur (30). Özellikle kanama komplikasyonu %1.2-3.9 oranlarında ölümcül olabilmektedir (30,31). Kanama dışında ateş, anafilaksi, karaciğer enzimlerinde yükselme diğer yan etkilerindendir (32).…”

Heparin-induced Thrombocytopenia in the ICU: An Overview

“…Nevertheless, the incidence of thromboembolic complications was shown to be higher in patients treated with argatroban than in those who were treated with lepirudin or danaparoid. Th is was explained, however, by the shorter duration of argatroban therapy compared to lepirudin [40].…”

“…Alternative therapeutic anticoagulation should be initiated based on a high clinical suspicion and not delayed while awaiting confi rmatory laboratory testing or because of thrombocytopenia [39]. When treatment was delayed pending laboratory confi rmation of the diagnosis within a clinical trial setting, the incidence of new thrombosis was approximately tenfold higher than during the subsequent period of treatment with a direct thrombin inhibitor [40]. Th erapeutic options include direct thrombin inhibitors and factor Xa inhibitors.…”