TxA2 Receptor‐Based Vaccination: A Novel Potential Therapeutic Approach to Limit Thrombosis

Abstract

Aberrant intravascular platelet activation leads to thrombosis, which is the most common cause of ischemic heart attack and stroke. At the site of vascular injury, platelet activation and aggregation lead to the first wave of thrombin, a potent platelet activator, generation which helps in thrombus stabilization.1 Apart from thrombin, activated platelets also release ADP and arachidonic acid as secondary mediators that potentiate platelet activation and aggregation. The platelet activation and aggregation cascade is initiated by a variety of platelet receptors including G protein–coupled and other transmembrane receptors, such as protease‐activated receptors (PAR1/4), P2Y12, glycoprotein (GP) VI and Ib/IX/V, integrin αIIbβ3, and thromboxane A2 (TxA2) receptor (TPR).2 These receptors and other platelet‐signaling molecules have been extensively targeted to identify the novel antithrombotic targets, and these efforts, in fact, led to the development of several small molecule inhibitors.3 Of these, some are already being used in the clinic (eg, aspirin, clopidogrel) to prevent or limit the reoccurrence of thrombosis, and others are being tested for therapeutic efficacy and are at different levels of clinical trials. The major limitation of these antiplatelet agents involves the increased risk of bleeding in patients. Consequently, better and safer therapeutic strategies are needed to limit thrombotic and cardiovascular events.