Factor VIII inhibitor-bypassing agents act by inducing thrombin generation and can be monitored by a thrombin generation assay

被引:98
作者
Turecek, PL
Váradi, K
Keil, B
Negrier, C
Berntorp, E
Astermark, J
Bordet, JC
Morfini, M
Linari, S
Schwarz, HP
机构
[1] Baxter BioSci, AT-1221 Vienna, Austria
[2] Hop Edouard Herriot, Lyon, France
[3] Malmo Univ Hosp, Malmo, Sweden
[4] Azienda Osped Careggi, Florence, Italy
关键词
FEIBA; factor VIIa; haemophilia A; inhibitor; thrombin generation; prothrombinase; activated prothrombin complex;
D O I
10.1159/000071637
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Factor VIII (FVIII)-bypassing agents have complex modes of action but all control bleeding in inhibitor patients by triggering the generation of thrombin. No routine test is available for monitoring this therapy in patients with inhibitors against FAIL We present an assay that records FEIBA- or FVIIa-mediated changes in thrombin generation (TG) in FVIII inhibitor plasma samples. In plasma samples spiked with FEIBA TG was normalized above 0.4 U/ml, while for recombinant FVIIa (rFVIIa) more than 12.5 mug/ml were required to induce TG in the absence of tissue factor (TF). Addition of TF increased the TG potential of rFVIIa in vitro. This assay seems suitable for monitoring the pharmacokinetics of inhibitor bypassing agents during treatment and possibly for predicting responses to treatment. Copyright (C) 2003 S. Karger AG, Basel.
引用
收藏
页码:16 / 22
页数:7
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