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阿加曲班和比伐卢定与普通肝素比较预防机械心脏瓣膜血栓形成。一项体外研究的结果。

Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves. Results of an in-vitro study.

机构信息

Department of Internal Medicine III, Martin Luther-University, Ernst-Grube-Str. 40, 06097 Halle, Germany.

出版信息

Thromb Haemost. 2009 Jun;101(6):1163-9.

PMID:19492162
Abstract

Prevention of valve thrombosis in patients after prosthetic mechanical heart valve replacement and heparin-induced thrombocytopenia (HIT) is still an open issue. The aim of the present in-vitro study was to investigate the efficacy of argatroban and bivalirudin in comparison to unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves. Blood (230 ml) from healthy young male volunteers was anticoagulated either by UFH, argatroban bolus, argatroban bolus plus continuous infusion, bivalirudin bolus, or bivalirudin bolus plus continuous infusion. Valve prostheses were placed in a newly developed in-vitro thrombosis tester and exposed to the anticoagulated blood samples. To quantify the thrombi, electron microscopy was performed, and each valve was weighed before and after the experiment. Mean thrombus weight in group 1 (UFH) was 117 + 93 mg, in group 2 (argatroban bolus) 722 + 428 mg, in group 3 (bivalirudin bolus) 758 + 323 mg, in group 4 (argatroban bolus plus continuous infusion) 162 + 98 mg, and in group 5 (bivalirudin bolus plus continuous infusion) 166 + 141 mg (p-value <0.001). Electron microscopy showed increased rates of thrombus formation in groups 2 and 3. Argatroban and bivalirudin were as effective as UFH in preventing thrombus formation on valve prostheses in our in-vitro investigation when they were administered continuously. We hypothesise that continuous infusion of argatroban or bivalirudin are optimal treatment options for patients with HIT after mechanical heart valve replacement for adapting oral to parenteral anticoagulation or vice versa.

摘要

预防人工机械心脏瓣膜置换术后患者的瓣膜血栓形成和肝素诱导的血小板减少症(HIT)仍然是一个未解决的问题。本体外研究的目的是比较阿加曲班和比伐卢定与普通肝素(UFH)在预防机械心脏瓣膜上血栓形成的疗效。用 UFH、阿加曲班推注、阿加曲班推注加持续输注、比伐卢定推注或比伐卢定推注加持续输注抗凝的健康年轻男性志愿者的血液(230ml)。将瓣膜假体放置在新开发的体外血栓测试仪中,并将其暴露于抗凝血液样本中。为了定量血栓,进行电子显微镜检查,并在实验前后对每个瓣膜进行称重。第 1 组(UFH)的平均血栓重量为 117+93mg,第 2 组(阿加曲班推注)为 722+428mg,第 3 组(比伐卢定推注)为 758+323mg,第 4 组(阿加曲班推注加持续输注)为 162+98mg,第 5 组(比伐卢定推注加持续输注)为 166+141mg(p 值<0.001)。电子显微镜显示第 2 组和第 3 组血栓形成率增加。在我们的体外研究中,当连续给予阿加曲班或比伐卢定时,它们在预防瓣膜假体上血栓形成方面与 UFH 同样有效。我们假设在机械心脏瓣膜置换术后发生 HIT 的患者中,连续输注阿加曲班或比伐卢定是适应口服到静脉抗凝或反之亦然的最佳治疗选择。

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