The factor VII-platelet interplay: effectiveness of recombinant factor VIIa in the treatment of bleeding in severe thrombocytopathia.
Recently, high-dose factor VIIa has been used to correct bleeding in patients with various thrombocytopathias including Glanzmann's thrombasthenia, Bernard-Soulier syndrome, and uremia. High-dose factor VIIa is postulated to act on platelets in the absence of tissue factor to activate factors IX and X and thus enhance thrombin generation. This enhanced thrombin generation might help provide hemostasis in patients with thrombocytopathias through several mechanisms. Enhanced thrombin generation would provide a strong signal for recruitment of other platelets. Also, enhanced fibrin deposition might provide mechanisms for bypassing the specific defect in thrombocytopathias. Thus, platelets from a patient with Bernard-Soulier syndrome might associate with fibrin by a glycoprotein IIb-IIIa-mediated mechanism. Also, platelets from a patient with Glanzmann's thrombasthenia might associate with fibrin through von Willebrand factor-mediated interactions with glycoprotein Ib-V-IX. Finally, enhanced thrombin generation on platelets would mean that fewer platelets are required for hemostasis.
Monroe
D M
DM
Center for Thrombosis and Hemostasis, UNC School of Medicine, Chapel Hill, North Carolina, USA. dmonroe@med.unc.edu
Hoffman
M
M
Allen
G A
GA
Roberts
H R
HR
D001791:Blood Platelet Disorders / Q000188:drug therapy* / Q000503:physiopathology; D001792:Blood Platelets / Q000502:physiology*; D005167:Factor VII / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D015942:Factor VIIa; D006470:Hemorrhage / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*
D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa