On the mechanism of action of recombinant activated factor VII administered to patients with severe thrombocytopenia and life-threatening haemorrhage: focus on prothrombin activation.
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 microg/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.
Gerotziafas
Grigoris T
GT
Department of Haematology, Theagenion Cancer Hospital, 2.A. Simeonidi Street, 54161 Thessaloniki, Greece. gerotziafasgrigoris@hotmail.com
Zervas
Kostas
K
Arzoglou
Pantelis
P
Karavaggeli
Eli
E
Parashou
Stella
S
Van Dreden
Patrick
P
Christakis
John
J
Samama
Meyer Michel
MM
D015153:Blotting, Western; D005167:Factor VII / Q000627:therapeutic use*; D015942:Factor VIIa; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011516:Prothrombin / Q000378:metabolism*; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013917:Thrombin / Q000096:biosynthesis; D013921:Thrombocytopenia / Q000097:blood / Q000188:drug therapy*
D011994:Recombinant Proteins; D005167:Factor VII; D011516:Prothrombin; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin