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-granules 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-granules of normal platelets. Although the molecular basis of the disease is unknown, evidence suggests that alpha-granules 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 collagen 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-granules and of the storage of growth factors and secretable proteins.
Nurden
Alan T
AT
IFRN 4/CRPP, Laboratoire d'Hématologie, Hôpital Cardiologique, 33604 Pessac, France. Alan.nurden@cnrshl.u-bordeaux2.fr
Nurden
Paquita
P
D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008533:Megakaryocytes / Q000378:metabolism / Q000473:pathology*; D010974:Platelet Aggregation; D055728:Primary Myelofibrosis / Q000209:etiology; D011506:Proteins / Q000378:metabolism; D011696:Purpura, Thrombocytopenic / Q000235:genetics / Q000503:physiopathology; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics* / Q000473:pathology
D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins