重组水蛭素用于肝素诱导的血小板减少症患者的胃肠外抗凝治疗。肝素相关性血小板减少症研究（HAT）调查组。

Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-Associated Thrombocytopenia Study (HAT) investigators.

作者信息

Greinacher A, Janssens U, Berg G, Böck M, Kwasny H, Kemkes-Matthes B, Eichler P, Völpel H, Pötzsch B, Luz M

机构信息

Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany.

出版信息

Circulation. 1999 Aug 10;100(6):587-93. doi: 10.1161/01.cir.100.6.587.

DOI:10.1161/01.cir.100.6.587

PMID:10441094

Abstract

BACKGROUND

We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT).

METHODS AND RESULTS

Patients with confirmed HIT (n=112) received lepirudin according to need for 2 to 10 days (longer if necessary): A1, treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg. kg(-1). h(-1) intravenous infusion, n=65; A2, treatment in conjunction with thrombolysis: 0.2 mg/kg, followed by 0.10 mg. kg(-1). h(-1), n=4; and B, prophylaxis: 0.10 mg. kg(-1). h(-1), n=43. Outcomes from 95 eligible lepirudin-treated patients were compared with those of historical control patients (n=120). Complete laboratory response (activated partial thromboplastin time ratio >1.5 with </=2 dose increases and platelet count normalization by day 10) was achieved in 65 lepirudin-treated patients (69.1%; 95% CI, 59. 3% to 78.3%). At 2 weeks after cessation of lepirudin, 11 patients died (9.8%), 10 underwent limb amputation (8.9%), and 20 suffered a new thromboembolic complication (17.9%). The average combined event rate per patient-day decreased from 5.1% in the pretreatment period to 1.5% in the treatment period. Thirty-five days after HIT confirmation, fewer lepirudin-treated patients than historical control patients had experienced >/=1 outcome (cumulative incidence 30.9% versus 52.1%; relative risk [RR] 0.71; P=0.12, log-rank test). Bleeding events were more frequent in the lepirudin group than the historical control group (cumulative incidence at 35 days, 44.6% versus 27.2%; RR 2.57; P=0.0001, log-rank test). No difference was observed in bleeding events requiring transfusion (cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66; P=0.23, log-rank test); no intracranial bleeding was observed in the lepirudin group.

CONCLUSIONS

Lepirudin effectively prevents death, limb amputations, and new thromboembolic complications and has an acceptable safety profile in HIT patients. Treatment should be initiated as soon as possible if HIT is suspected.

摘要

背景

我们前瞻性地研究了比伐芦定在肝素诱导的血小板减少症（HIT）患者中进一步进行胃肠外抗凝的作用。

方法与结果

确诊为HIT的患者（n = 112）根据需要接受比伐芦定治疗2至10天（必要时延长）：A1组，治疗：静脉推注0.4 mg/kg，随后以0.15 mg·kg⁻¹·h⁻¹静脉输注，n = 65；A2组，与溶栓联合治疗：0.2 mg/kg，随后以0.10 mg·kg⁻¹·h⁻¹，n = 4；B组，预防：0.10 mg·kg⁻¹·h⁻¹，n = 43。将95例符合条件的接受比伐芦定治疗的患者的结果与历史对照患者（n = 120）的结果进行比较。65例接受比伐芦定治疗的患者（69.1%；95%CI，59.3%至78.3%）实现了完全实验室反应（活化部分凝血活酶时间比值>1.5，剂量增加≤2次且第10天血小板计数正常化）。在停用比伐芦定2周后，11例患者死亡（9.8%），10例接受肢体截肢（8.9%），20例发生新的血栓栓塞并发症（17.9%）。每位患者每天的平均联合事件发生率从治疗前期的5.1%降至治疗期的1.5%。在确诊HIT 35天后，经历≥1次结局的接受比伐芦定治疗的患者少于历史对照患者（累积发生率30.9%对52.1%；相对风险[RR]0.71；P = 0.12，对数秩检验）。比伐芦定组的出血事件比历史对照组更频繁（35天时的累积发生率，44.6%对27.2%；RR 2.57；P = 0.0001，对数秩检验）。在需要输血的出血事件方面未观察到差异（35天时的累积发生率，12.9%对9.1%；RR 1.66；P = 0.23，对数秩检验）；比伐芦定组未观察到颅内出血。