An hypothesis on the consolidation and PGE1-induced deconsolidation of a platelet plug

Abstract

Consolidation is the final stage in haemostasis in which a platelet plug blocking a bleeding area of a vessel: (a) becomes impermeable to circulating plasma proteins and (b) contracts to resist blood pressure. Hypothesis: The impermeabilization step of consolidation is accomplished through fluid uptake by the platelets from a hydrated intercellular glue formed during thrombin activation. Dehydration occurs through inhibition of the Na⁺,K⁺-ATPase of platelets with sodium and water uptake. However, and uniquely, due to the high cellular density of the platelet plug, access of peripheral plasma fluids to the plug is limited forcing the platelets to take up preferentially the fluid of the interplatelet space. The increased adhesion properties of the dehydrated glue simultaneously furthers a decreased hydraulic permeability and an improved coupling of the contractile forces among platelets. In ‘Deconsolidation’, the fluid uptake process can be reversed and amplified by agents that increase cAMP, reactivating the Na⁺,K⁺-ATPase and expressing CFTR or equivalent Cl⁻ secretory channels that force the extrusion of fluid from the platelets, with rehydration of the intercellular polymer and a large increase in the interplatelet space.