Heparin, Prostaglandins, and von Willebrand Disease: Interactions in Hemostasis and Clinical Implications
Abstract Hemostasis depends on coordinated platelet adhesion and activation, coagulation-factor activity, thrombin generation, fibrin formation, and endogenous anticoagulant mechanisms. Von Willebrand factor (VWF), prostanoid signaling, platelet factor 4 (PF4), and heparin affect distinct components of this system. VWF mediates platelet adhesion to damaged vascular surfaces and stabilizes coagulation factor VIII (FVIII). Quantitative or qualitative VWF abnormalities cause von Willebrand disease (VWD). Prostanoid signaling regulates platelet and vascular activity; platelet-derived thromboxane A₂ (TXA₂) promotes platelet activation and aggregation, whereas endothelial prostacyclin (PGI₂) inhibits platelet activation and promotes vasodilation. Aspirin suppresses platelet TXA₂ synthesis and can therefore increase bleeding in VWD. PF4 (CXCL4) is a cationic chemokine stored in platelet α-granules and released during platelet activation. PF4 binds strongly to heparin. In susceptible individua...