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On the mechanism of action of recombinant activated factor VII administered to patients with severe thrombocytopenia and life‐threatening haemorrhage: focus on prothrombin activation
Author(s) -
Gerotziafas Grigoris T.,
Zervas Kostas,
Arzoglou Pantelis,
Karavaggeli Eli,
Parashou Stella,
Van Dreden Patrick,
Christakis John,
Samama Meyer Michel
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03437.x
Subject(s) - partial thromboplastin time , medicine , recombinant factor viia , prothrombin time , thromboplastin , platelet , recombinant dna , thrombin time , activated clotting time , clotting time , thrombin , thrombin generation , coagulation , pharmacology , factor vii , platelet activation , tissue factor , ex vivo , anesthesia , immunology , anticoagulant , in vivo , chemistry , biochemistry , biology , gene , microbiology and biotechnology
Summary. We report the ex vivo effect of recombinant activated factor VII (rFVIIa) on prothrombin activation after whole blood clotting. Two patients with severe thrombocytopenia and life‐threatening haemorrhage were successfully managed using a single dose of rFVIIa (90 µg/kg). Western blotting using antiprothrombin antibody showed that rFVIIa did not induce thrombin generation in citrated platelet‐poor plasma. Patient sera showed significantly impaired prothrombin activation before and after rFVIIa administration. rFVIIa administration shortened the prothrombin time, activated partial thromboplastin time and Ivy bleeding time, and normalized the clot retraction. These data indicate that rFVIIa accelerated thrombin generation without significant increase of generated thrombin.