Factor VIIa-catalyzed activation of factor X independent of tissue factor: its possible significance for control of hemophilic bleeding by infused factor VIIa

摘要: Infusing factor VIIa (FVIIa) has been reported to control bleeding in hemophilic patients with VIII (FVIII) inhibitors. This is difficult attribute an enhanced FVIIa/tissue (TF) activation of X, since vitro studies suggest that infusion FVIIa should neither increase substantially the rate formation FVIIa/TF complexes during hemostasis (Proc Natl Acad Sci USA 85:6687, 1988) nor bypass dampening TF-dependent coagulation by extrinsic pathway inhibitor (EPI) (Blood 73:359, 1989). Partial thromboplastin times have also shorten after FVIIa. The experiments herein establish shortening partial adding plasma stems from FVIIa-catalyzed X independent possible trace contamination reagents TF. Experiments purified systems confirmed can slowly activate a reaction mixture containing Ca2+ and phospholipid but no source was sufficient account for observed. EPI, which turned off continuing unable prevent FVIIa/phospholipid X. Because circulating contains only trace, if any, free FVIIa, such could never occur physiologically. However, infusing creates nonphysiologic circumstance slow catalyzed conceivably proceed vivo unimpeded EPI. Such mechanism might compensate impaired IXa/FVIIIa/phospholipid hemostatis, therefore patient.