REVERSIBLE DEFICIENCY OF INTACT THROMBOSPONDIN AND MEMBRANE GLYCOPROTEIN Ia IN PLATELETS OF A PATIENT WITH A BLEEDING DISORDER

A 52 year old female patient with a severe bleeding tendency since the age of two was studied. Her history revealed recurrent petechial bleedings, two severe postoperative haemorrhagic episodes and intensivemenstrual bleedings which required blood transfusions. Coagulation studies ruled out any coagulation disorder including von Willebrand's disease. Platelet count and morphology(using light and electron microscopy) were normal. The patient had prolonged bleeding times (up to 15 min). Her platelets aggregated normally in response to ADP, arachidonic acid, thrombin, ionophore A 23187, epinephrine and ristocetin. In contrast, platelet aggregation in the presence of collagen and wheat germ agglutinin could only be achieved with very high doses of these agonists. Repeated analyses of the patient's platelet proteins by two-dimensional 0'Farrel gel electrophoresis followed by silver staining or blotting onto nitrocellulose and staining with a mixture of peroxidase-coupled lectins showed that glycoprotein la and intact thrombospondin were absent. An immunoblot for thrombospondin showed several proteins with lower molecular weight than thrombospondin. Preincubation of the patient's platelets with thrombospondin normalized collagen-induced aggregation.At a recent follow-up examination the patient had no petechial bleedings. Platelet protein analysis revealed thatintact thrombospondin and glycoprotein la were present. These results suggest that both glycoprotein la and thrombospondin have essential roles in collagen-induced platelet aggregation.