IMPAIRED PROTHROMBIN CONSUMPTION IN BERNARD-SOULIER SYNDROME IS CORRECTED IN-VITRO BY HUMAN FACTOR-VIII

The Bernard-Soulier syndrome (BSS) is characterized by thrombocytopeni a with giant platelets, a prolonged bleeding time with defective plate let adhesion to the subendothelium related to a defect in platelet mem brane glycoprotein Ib (GPIb) and a decreased prothrombin consumption. The mechanism of the latter abnormality remains unknown. In this study , we showed that this defect was corrected by the addition of purified human factor VIII (FVIII) to blood from four patients with BSS. The c orrection of prothrombin consumption was almost complete at concentrat ions between 1.5 and 3 IU/ml of FVIII procoagulant activity (VIII:C) a nd partially abolished by a monoclonal antibody which neutralizes VIII :C. This correction was specific for FVIII and was not observed after addition of purified human FIX. It was obtained, in the same magnitude range, with FVIII complexed to von Willebrand factor (vWF) but not wi th free vWF. These data provide a new insight into the knowledge of th e physiological interaction between the platelet membrane and the vWF- FVIII complex facilitating plasma coagulation activation and may lead to helpful therapeutic advances.