James N. George

Bernard-Soulier Disease: a Study of Four Patients and their Parents

Summary. 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 FVIIvWF 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 anormally 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.

Quantitative analysis of platelet membrane glycoproteins: Effect of platelet washing procedures and isolation of platelet density subpopulations

Abstract Many procedures for the analysis of platelet proteins use platelets isolated by washing in protein-free buffers. We examined platelet glycoproteins after isolation by two washes in albumin-containing buffer (with 92% recovery of total whole blood platelets) and compared these to the platelets washed an additional four times in protein-free buffer (37% recovery of total whole blood platelets). Platelet recoveries were checked by three methods of quantitation (electronic particle counter, phase microscopy, and optical density) and equal results were obtained with each method. Platelet glycoproteins were quantitatively analyzed with polyacrylamide gel electrophoresis in sodium dodecyl sulfate and staining by the periodic acid-Schiff reaction. The concentration per platelet of the granule glycoprotein (GP-G) and all four major membrane glycoproteins was significantly decreased (by 30–43%, p

The Role of Membrane Glycoproteins in Platelet Formation, Circulation, and Senescence

Circulating blood platelets are required to form an immediate hemostatic plug at the site of a vascular endothelial gap. The properties of the platelet membrane glycoproteins related to the specific functions of adhesion and aggregation during this hemostatic reaction have been the focus of the preceding chapters of this book. This chapter will review current knowledge and hypotheses on the broader and less defined phenomena of platelet production from megakaryocytes and their appearance in the circulation, their lifespan and senescence, and finally their ultimate removal from the circulation. Each of these events seems to involve membrane contact phenomena that are unique to the platelet: (1) within the bone marrow the megakaryocyte occupies a special position adjacent to the sinusoidal wall; (2) platelets are released from fragmenting megakaryocyte cytoplasm either within the marrow sinuses or later within the pulmonary capillaries; (3) circulating platelets undergo reversible adhesion encounters during their lifespan, losing fragments of their surface membrane in the process; and (4) finally an unknown senescent change on the surface membrane signals the ultimate sequestration of the platelet. This entire process may be viewed as a sequence of reversible contact interactions among platelets as well as between platelets and the vessel wall resulting in surface glycoprotein changes and membrane fragmentation.