Structural defects in inherited and giant platelet disorders

Abstract

As diverse as the group of inherited structural defects and giant platelet disorders presented in this chapter may seem, there is a common thread that ties them together. All appear to represent some form of membrane aberration. Sometimes only a small inclusion identifies the membrane defect, sometimes a massive increase in size. In others, whole populations of organelles are missing or surface membranes lack specific glycoproteins essential for their function. All of them are born in the deep recesses of a hidden cell, the bone marrow megakaryocyte. Getting the megakaryocyte out into the light of day, or at least into a culture medium, should certainly lead to the solution of many, if not all, of the disorders of platelet membranes and membrane disorders. We have not been completely succesful in our efforts to study the megakaryocyte in vitro. As a result, we do not yet understand the normal megakaryocyte, much less normal platelet. The megakaryocyte presents one of the greatest of challenges to our understanding of membrane biology. As our knowledge of how its cytoplasm fills with interiorly and exteriorly derived membranes, and the mechanisms underlying their organization into platelet surfaces, channels of the OCS and DTS, membrane complexes, and five kinds of organelles become clear, our ability to define the basic nature and inheritance of defects will improve rapidly. Within the next decade most aspects of platelet molecular genetics and cell biology will be solved.