Abstract

Inherited platelet disorders constitute a large group of diseases involving a wide range of genetic defects that can lead to bleeding symptoms of varying severity. They are associated with defects in surface membrane glycoproteins resulting in e.g. Bernard Soulier Syndrome and Glanzmann Thrombasthenia causing defects in platelet adhesion and aggregation, respectively, as well as in receptors for agonists (a.o. P2Y(12), TXA(2)) disrupting platelet signalling. Defects affecting platelet granules can be characterised by abnormalities of alpha-granules as in the Gray platelet syndrome or dense granules as in Hermansky-Pudlak and Chediak-Higashi syndromes, the latter two also altering other cytoplasmic organelles such as melanosomes and therefore not restricted to platelets. Finally, defects in proteins essential to signalling pathways (a.o. in Wiskott-Aldrich syndrome) or in platelet-derived procoagulant activity (Scott and Stormorken syndromes) also impair platelet function. For most of the above disorders mouse knockout models have been generated, that allowed to confirm the genotype-phenotype relationship and to further unravel the molecular causes of the disease and the mechanisms underlying primary haemostasis. More recently, interest has been growing in the effects of the more common polymorphisms that are found in the platelet glycoproteins as possible risk factors for thrombotic disorders. The new era of platelet genomics and proteomics will increase our knowledge on platelet disorders that will improve their diagnosis, but also will provide basis for new antithrombotic therapies.