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

Turecek, PL; Varadi, K; Keil, B; Negrier, C; Berntorp, Erik LU ; Astermark, Jan LU ; Bordet, JC; Morfini, M; Linari, S and Schwarz, HP (2003) In Pathophysiology of Haemostasis and Thrombosis 33(1). p.16-22
Abstract
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 FVIII. 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... (More)
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 FVIII. 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
prothrombinase, thrombin generation, FEIBA, activated prothrombin complex, inhibitor, factor VIIa, haemophilia A
in
Pathophysiology of Haemostasis and Thrombosis
volume
33
issue
1
pages
16 - 22
publisher
Karger
external identifiers
  • wos:000184774300004
  • pmid:12853708
  • scopus:10744231994
ISSN
1424-8832
DOI
10.1159/000071637
language
English
LU publication?
yes
id
8b6ae16e-c263-4c16-89fa-5a8050fcaa95 (old id 899776)
date added to LUP
2008-01-16 10:41:03
date last changed
2018-10-03 11:43:56
@article{8b6ae16e-c263-4c16-89fa-5a8050fcaa95,
  abstract     = {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 FVIII. 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.},
  author       = {Turecek, PL and Varadi, K and Keil, B and Negrier, C and Berntorp, Erik and Astermark, Jan and Bordet, JC and Morfini, M and Linari, S and Schwarz, HP},
  issn         = {1424-8832},
  keyword      = {prothrombinase,thrombin generation,FEIBA,activated prothrombin complex,inhibitor,factor VIIa,haemophilia A},
  language     = {eng},
  number       = {1},
  pages        = {16--22},
  publisher    = {Karger},
  series       = {Pathophysiology of Haemostasis and Thrombosis},
  title        = {Factor VIII inhibitor-bypassing agents act by inducing thrombin generation and can be monitored by a thrombin generation assay},
  url          = {http://dx.doi.org/10.1159/000071637},
  volume       = {33},
  year         = {2003},
}