Tissue factor and factor VIIa as therapeutic targets in disorders of hemostasis.
For hemophilia patients with inhibitors against FVIII or FIX, the development of recombinant factor VIIa (rFVIIa) raises the possibility of a therapeutic alternative whose availability and convenience of treatment are comparable to those of FVIII or FIX. In support of this new concept for the treatment of bleeding episodes, pharmacological doses of FVIIa have been shown to induce hemostasis. Pharmacological doses of rFVIIa enhance thrombin generation on thrombin-activated platelets, thereby facilitating the formation of strong, well-structured fibrin plugs resistant to premature proteolysis. Modified rFVIIa molecules with a stronger hemostatic potential have been produced. Inhibition of the FVII-TF-dependent pathway (TFPI and rFVIIai) has been tried in attempts to prevent thrombosis, with promising results in animal models so far not confirmed in clinical trials.
Hedner
Ulla
U
Department of Medicine, University of Lund, Sweden. UHe@novonordisk.com
Ezban
Mirella
M
D015942:Factor VIIa / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D020141:Hemostatic Disorders / Q000188:drug therapy* / Q000209:etiology; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use; D013925:Thromboplastin / Q000627:therapeutic use*
D006490:Hemostatics; D011994:Recombinant Proteins; D013925:Thromboplastin; C103587:recombinant FVIIa; D015942:Factor VIIa