Are Procoagulant Platelets an Emerging Therapeutic Target? A General Review with an Emphasis on Their Clinical...

Platelets carry out their aggregatory and procoagulant roles in two distinct phenotypes. Aggregatory platelets initiate adhesion to the injured endothelium and extend the platelet plug, where procoagulant platelets accelerate thrombin formation and fibrinogen cleaving by exposing a procoagulant-rich outer membrane that facilitates coagulation factor assembly. Conventional anti-platelet therapies inhibit the aggregatory phenotype but fall short on restraining procoagulant platelets. Although procoagulant platelets are crucial for normal hemostasis, a shift toward excess procoagulant platelets is associated with human thrombotic disorders such as ischemic stroke. Although veterinary data is limited, recent studies show that feline and canine platelets display similar procoagulant phenotypes in response to potent agonists, suggesting that procoagulant platelets may play similar roles in the pathogenesis of thromboembolic disorders in veterinary species. Species-specific differences in platelet physiology and molecular structures, however, pose significant challenges. This review aims to (1) summarize cross-species evidence on the mechanisms driving procoagulant platelet formation, their defining features, and characteristics, (2) provide perspectives on procoagulant platelets as thrombotic biomarkers and outline the technical challenges of generating and detecting them in small animal medicine, and (3) summarize potential therapeutic targets and highlight priority research areas to advance the diagnosis and management of thromboembolic diseases in veterinary medicine.