It has been reported recently that DDAVP might be an useful tool in the therapy and prevention of bleeding in patients with congenital afibrinogenemia (CA).To study the mechanism of its efficacy, changes in the platelet functions of a patient with CA were examined prior to, and one hour after, the infusion of DDAVP (0.4 μg/Kg). A patient with Glanzmann's thrombasthenia (GT) was also examined, to allow a study of the role of platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa), a deficient platelet in GT, in the resulting effects of the drug. When both patients were infused with DDAVP, the level of plasma von Willebrand factor (vWF) increased two- to fourfold, accompanied by an enhancement of ristocetin-induced platelet agglutination. The level of plasma fibrinogen was never changed.The prolonged bleeding time observed was markedly improved only in the CA patient, remaining unchanged in the GT patient, after the infusion of DDAVP. This indicates that DDAVP is effective in diminishing the bleeding tendency in CA, but not in GT. Among the platelet functions tested, only the platelet retention rate on glass beads, ADP-induced platelet aggregation and collagen-induced platelet aggregation improved in CA, each remaining unchanged in GT. In particular, collagen-induced platelet aggregation was markedly improved in the CA patient. However, the platelet adhesion to collagen (50 μg/ml)-Sepharose remained normal, both before and after the infusion of DDAVP in CA.These results suggest that an increase in the plasma vWF level and the existence of platelet membrane GPIIb/IIIa may be necessary for the improvement of primary hemostasis, after the infusion of DDAVP. The vWF-mediated platelet aggregation by collagen or ADP may produce this effect in the CA patient.
Heterogeneity of congenital afibrinogenemia, from epidemiology to clinical consequences and management
