Molecular mechanisms underlying the platelet procoagulant response: back to basics

Differently sized platelets are present during activated coagulation, such as aggregated cells, activated clotting platelets and platelet-fibrinogen interactions. The stability of a blood clot is determined by the generation of a coagulation-active surface and the inactivation of integrin receptors. Platelets increase their surface area through balloon formation to improve the binding capacity of coagulation factors.

Patients with Scott syndrome, a rare congenital bleeding disorder, and a defect in the protein anoctamine-6 have platelets with significantly reduced blood coagulation. Using in-vitro and ex-vivo experiments and genetically modified mice, we found a direct link between the presence of anoctamine-6 and the development of coagulation-active platelets and haemorrhage. The absence of anoctamine-6 results in several changes to the protein levels of Scott platelets, which may explain this complex phenotype.