The mechanism of action of
recombinant factor VIIa (
rFVIIa), which is being considered as an alternative treatment for the control of
bleeding episodes in patients with
thrombocytopenia, has not been fully characterized. This study was undertaken to explore the effects of
rFVIIa and platelet microvesicles on hemostasis in an experimental model of
thrombocytopenia. Damaged arterial segments were exposed to thrombocytopenic blood (shear rate 600 s(-1)) either with or without the addition of
rFVIIa and/or platelet microvesicles. The presence of
fibrin and platelets on the subendothelium were morphometrically quantified and immunolocalization techniques and electron microscopy were used for a more detailed analysis. Both
rFVIIa and platelet microvesicles consistently improved
fibrin formation on the damaged vascular subendothelium, and microvesicles were shown to be localized at different levels of the
fibrin lattice. Further, under conditions of moderate
thrombocytopenia, addition of platelet microvesicles potentiated the procoagulant action of
rFVIIa. This effect may be due to the
phospholipid surface provided by the platelet microvesicles. These studies support the concept that, under conditions of
thrombocytopenia, both
rFVIIa and platelet microvesicles enhance
fibrin formation at sites of vascular damage.