The gray platelet syndrome: Clinical spectrum of the disease

The gray platelet syndrome (GPS) is a rare inherited disorder of the megakaryocyte (MK) lineage. Thrombocytopenia and enlarged platelets are associated with a specific absence of alpha-granutes and their contents. GPS patients exhibit much heterogeneity both in bleeding severity and in their response to platelet function testing. A unique feature is that proteins endogenously synthesised by megakaryocytes (MK) or endocytosed by MK or platelets fail to enter into the secretable storage pools that characterise alpha-granutes of normal platelets. Although the molecular basis of the disease is unknown, evidence suggests that alpha-granutes simply fail to mature during MK differentiation. One result is a continued leakage of growth factors and cytokines into the marrow causing myelofibrosis. While for some patients platelet function may be only moderately affected, for others thrombin and/or collagen-induced platelet aggregation is markedly modified and an acquired lack of the GPVI cottagen receptor has been reported. In this review, we document the clinical and molecular heterogeneity in GPS, a unique disease of the biogenesis of platelet alpha-granutes and of the storage of growth factors and secretable proteins. (c) 2005 Elsevier Ltd. All rights reserved.