Effects of prothrombin complex concentrate and recombinant activated factor VII on vitamin K antagonist induced anticoagulation
Effects of prothrombin complex concentrate and recombinant activated factor VII on vitamin K antagonist induced anticoagulation
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DOI：
10.1016/j.thromres.2007.09.002
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发表时间：
2008-01-01
影响因子：
7.5
通讯作者：
Levy, Jerrold H.
中科院分区：
文献类型：
--
作者：
Tanaka, Kenichi A.;Szlam, Fania;Levy, Jerrold H.
前言：华法林及其衍生物广泛用于预防血栓事件。凝血酶原复合物浓缩物（PCC）和重组活化因子VII（rFVIIa）已在临床上用于该药物的急性逆转，但有关这些止血干预措施的比较功效的数据很少。材料和方法：使用体内大鼠和体外人类抗凝模型，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作用，对口服苯丙香豆素（2.5 mg/kg）的大鼠给予生理盐水（对照）、PCC 50 U/ml（-1）或rFVIIa 100 μ g/ml（-1）。对于体外模型，将来自INR值为2.1-6.7的华法林治疗个体的血浆样本加标PCC（0.2、0.4或0.72 U ml（-1））或rFVIIa（3.0 μ g/ ml）。结果：苯丙香豆素对大鼠的给药延长了PT（14.7 +/- 0.5至50.43 +/- 0.7 s），并使凝血酶生成峰值降低了89 +/-2.3%。PCC剂量依赖性逆转华法林治疗的人血浆和苯丙香豆素治疗的大鼠的抗凝作用，缩短PT和增加凝血酶峰值水平。然而，rFVIIa只逆转PT，但对凝血酶峰值levels.Conclusion影响甚微：PCC和rFVIIa逆转华法林抗凝的基础上PT，但只有PCC恢复整体凝血酶生成。(C)2007爱思唯尔有限公司版权所有。
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 mu g 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 mu g/ ml). The treatments were evaluated using prothrombin time (PT) and thrombin generation (Thrombinoscope (TM)).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. (C) 2007 Elsevier Ltd. All rights reserved.