Factor VIII Inhibitor-Bypassing Agents Act by Inducing Thrombin Generation and Can Be Monitored by a Thrombin Generation Assay | Zendy

P. L. Turecek | Zendy; Katalin Váradi | Zendy; B. Keil | Zendy; Claude Négrier | Zendy; Erik Berntorp | Zendy; Jan Astermark | Zendy; JeanClaude Bordet | Zendy; Massimo Morfini | Zendy; Silvia Linari | Zendy; HP Schwarz | Zendy

Open Access

Factor VIII Inhibitor-Bypassing Agents Act by Inducing Thrombin Generation and Can Be Monitored by a Thrombin Generation Assay

Author(s) -

P. L. Turecek,

Katalin Váradi,

B. Keil,

Claude Négrier,

Erik Berntorp,

Jan Astermark,

JeanClaude Bordet,

Massimo Morfini,

Silvia Linari,

HP Schwarz

Publication year - 2003

Publication title -

pathophysiology of haemostasis and thrombosis

Language(s) - English

Resource type - Journals

eISSN - 1424-8840

pISSN - 1424-8832

DOI - 10.1159/000071637

Subject(s) - thrombin generation , thrombin , chemistry , pharmacology , discovery and development of direct thrombin inhibitors , direct thrombin inhibitor , medicine , immunology , warfarin , platelet , dabigatran , atrial fibrillation

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 microg/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.

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