During the haemostatic response, the formation of a primary platelet plug limits
bleeding and provides a surface for
clotting factors to assemble and become activated. The initial platelet plug is stabilized by
fibrin monomers, covalently cross-linked by FXIII, forming a platelets-
fibrin thrombus. Defects in platelets as well as inherited deficiencies of
coagulation factors including
fibrinogen, FII, FV, FV + FVIII, FVII, FX, FXI and FXIII deficiencies, generally lead to lifelong
bleeding disorders, whose severity of
bleeding symptoms is heterogeneous in platelets abnormalities but generally inversely proportional to the degree of the factor deficiency in rare
bleeding disorders (RBDs). The prevalence of platelet defects among the general population has not been established, whereas for RBDs it ranges from approximately 1 in 2 million to 1 in 500,000, being higher in countries where consanguineous marriages are diffused. As a consequence of the rarity of these deficiencies, the type and severity of
bleeding symptoms, the underlying molecular defects, and the actual management of
bleeding episodes are not well established. In this review the main features, diagnosis, available treatment options and treatment complications of the platelet disorders, caused by abnormalities in platelet receptors for adhesive
proteins, platelet receptors for soluble agonists, platelet granules, signal transduction pathways, or procoagulant
phospholipids will be discussed by Dr Cattaneo, whereas
fibrinogen deficiency and FXIII deficiency will be described by Dr Inbal and Dr de Moerloose, respectively. Finally, the update of the Rare
Bleeding Disorders Database will be presented by Dr Spreafico.