凝血酶原复合物浓缩剂和重组活化凝血因子 VII 对维生素 K 拮抗剂诱导的抗凝作用。

Effects of prothrombin complex concentrate and recombinant activated factor VII on vitamin K antagonist induced anticoagulation.

作者信息

Tanaka Kenichi A, Szlam Fania, Dickneite Gerhard, Levy Jerrold H

机构信息

Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.

出版信息

Thromb Res. 2008;122(1):117-23. doi: 10.1016/j.thromres.2007.09.002. Epub 2007 Oct 31.

DOI:10.1016/j.thromres.2007.09.002

PMID:17977586

Abstract

INTRODUCTION

Warfarin and its derivatives are widely used for prevention of thrombotic incidents. Prothrombin complex concentrate (PCC) and recombinant activated factor VII (rFVIIa) have been used clinically for the acute reversal of this agent but there is a paucity of data on comparative efficacies of these hemostatic interventions.

MATERIALS AND METHODS

Using in vivo rat and in vitro human models of anticoagulation, we compared PCC and rFVIIa on the recovery of endogenous thrombin generation. For in vivo reversal of anticoagulation, saline (control), PCC 50 U ml(-1), or rFVIIa100 mug ml(-1) was given to rats which received phenprocoumon (2.5 mg kg(-1)) orally. For in vitro model, plasma samples from warfarin-treated individuals with INR values of 2.1-6.7 were spiked with PCC (0.2, 0.4, or 0.72 U ml(-1)) or rFVIIa (3.0 mug/ml). The treatments were evaluated using prothrombin time (PT) and thrombin generation (Thrombinoscope).

RESULTS

Administration of phenprocoumon to rats prolonged PT (14.7+/-0.5 to 50.43+/-0.7 s) and decreased peak thrombin generation by 89+/-2.3%. Administration of PCC dose dependently reversed the anticoagulation effects both in warfarin-treated human plasma and in phenprocoumon-treated rats by shortening PT and increasing peak thrombin levels. However, rFVIIa only reversed PT, but had minimal effects on peak thrombin levels.

CONCLUSION

Both PCC and rFVIIa reverse warfarin anticoagulation based on PT, but only PCC restores overall thrombin generation.

摘要

引言

华法林及其衍生物广泛用于预防血栓形成事件。凝血酶原复合物浓缩物（PCC）和重组活化凝血因子VII（rFVIIa）已在临床上用于该药物的急性逆转，但关于这些止血干预措施的比较疗效的数据较少。

材料与方法

使用体内大鼠和体外人体抗凝模型，我们比较了PCC和rFVIIa对内源性凝血酶生成恢复的影响。为了在体内逆转抗凝，给口服苯丙香豆素（2.5 mg kg(-1)）的大鼠给予生理盐水（对照）、50 U ml(-1)的PCC或100 μg ml(-1)的rFVIIa。对于体外模型，将国际标准化比值（INR）值为2.1 - 6.7的华法林治疗个体的血浆样本加入PCC（0.2、0.4或0.72 U ml(-1)）或rFVIIa（3.0 μg/ml）。使用凝血酶原时间（PT）和凝血酶生成（凝血酶监测仪）评估治疗效果。