On the mechanism of action of recombinant activated factor VII administered to patients with severe thrombocytopenia and life‐threatening haemorrhage: focus on prothrombin activation

• Published in: British journal of haematology Vol. 117; no. 3; pp. 705 - 708
• Main Authors: Gerotziafas, Grigoris T., Zervas, Kostas, Arzoglou, Pantelis, Karavaggeli, Eli, Parashou, Stella, Van Dreden, Patrick, Christakis, John, Samama, Meyer Michel
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2002; Blackwell
• Subjects: Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Blotting, Western; Factor VII - therapeutic use; Factor VIIa; haemorrhage; Hematologic and hematopoietic diseases; Hemorrhage - blood; Hemorrhage - drug therapy; Hemostasis - drug effects; Humans; Medical sciences; Partial Thromboplastin Time; Pharmacology. Drug treatments; Platelet Count; Platelet diseases and coagulopathies; prothrombin; Prothrombin - metabolism; Prothrombin Time; recombinant factor VIIa; Recombinant Proteins - therapeutic use; Thrombin - biosynthesis; thrombin generation; thrombocytopenia; Thrombocytopenia - blood; Thrombocytopenia - drug therapy; Human; Thrombocytopenia; Serine endopeptidases; Enzyme; Thrombin; Hemopathy; Hemorrhage; Biological activity; Peptidases; Platelet; Treatment; Hemostasis; Prothrombin; Hydrolases; Recombinant protein; EC 3.4.21.5; Coagulation Factor VIIa
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2002.03437.x

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.