Bernard-Soulier disease: a study of four patients and their parents

Two families with Bernard-Soulier disease, including four patients and three of their parents, were studied and detailed clinical summaries are presented. One patient in each family has suffered severe bleeding problems while the other affected sibling is less severely affected. There has been no excessive bleeding in any of the parents or other family members. The patients demonstrated the abnormalities characteristic for Bernard-Soulier disease: thrombocytopenia, giant platelets, prolonged bleeding time, abnormal platelet aggregation to human FVIIIvWF and ristocetin or bovine FVIIIvWF alone, defective ristocetin-induced binding of human 125I-FVIIIvWF multimers, decreased platelet lysis by a drug-dependent antibody and complement, and a decreased concentration of membrane glycoprotein I. The parents had normal platelet counts, bleeding times, and FVIII-mediated aggregation. However, the parents had abnormally large platelets decreased sensitivity to lysis by a drug-dependent antibody and complement, and a decreased concentration of membrane glycoprotein I. Therefore the heterozygous state for Bernard-Soulier disease is recognizable by platelet membrane abnormalities although there is no defect of platelet function and no excessive bleeding. Red cell membrane proteins of one patient were normal, suggesting that phenotypic expression of the Bernard-Soulier disease defect is restricted to platelets.