Molecular and genetic basis of platelet disorders

The hemostatic system consists of platelets, coagulation factors, and the endothelial cells lining the blood vessels. The platelets arise from the cytoplasmic fragmentation of megakaryocytes in the bone marrow and circulate in blood as disk-shapeda nucleate particles. The inherited and congenital thrombocytopenias represent a very diverse group of disorders ranging from those with little or no hemorrhagic problems to those where significant mortality occurs within the neonatal period if appropriate therapy is not initiated. The inherited thrombocytopenias are very rare disorders compared with the congenital or acquired thrombocytopenias and making the correct diagnosis at the outset is very important as it usually avoids the prescribing of unnecessary and potentially toxic therapies. The differential diagnosis of neonatal thrombocytopenia differs enormously depending on the general well-being of the infant and therefore a detailed maternal history and neonatal examination are essential in making a speedy diagnosis. Platelet concentrate transfusions are the mainstay of therapy in the inherited group, whereas treating the underlying cause in the congenital group usually raises the platelet count into the normal range. The past 25 years have witnessed remarkable progress in the understanding, at the molecular level, of the mechanism(s) by which platelet production and survival is controlled. More recently, the molecular basis of MYH9-related disease has been elucidated. Despite these impressive breakthroughs, much remains to be learned about the molecular defects responsible for the majority of inherited thrombocytopenias. No doubt, the next 25 years will see not only the isolation of the rogue genes responsible for these conditions but also gene therapies for these disorders will become a reality.