DOI: 10.1097/MCA.0b013e328357d76f
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PMID: 22850479
Issn Print: 0954-6928
Publication Date: 2012/09/01
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Excerpt
While antiplatelet agents and anticoagulants are frequently discussed separately, it should be kept in mind that both thrombosis and hemostasis entail extensive interaction between activated platelets and the coagulation cascade. For instance, platelets are a key source of factor Va that initiates thrombin generation 3. In addition, the platelet surface amplifies the generation of thrombin 4. Thrombin, in turn, is one of the primary activators of platelets 5. Thus, any agent that limits platelet activation will also limit thrombin generation, and any agent that limits thrombin generation limits platelet activation. The extensive interaction between platelets and the coagulation cascade underscores the critical need for an endpoint assay that measures the summation of antithrombotic effect, reflecting both antiplatelet and anticoagulant effects.
In this review, new antithrombotic strategies are discussed in depth by experts in the field. Drs Barn and Steinhubl review new agents that block the ADP receptor P2Y12. Drs Wiisanen and Moliterno assess a new class of antiplatelet agents that block the binding of the tethered ligand to the protease activated receptor. The tethered ligand activates protease activated receptor receptors after cleavage by thrombin. The development of agents capable of achieving this end is a technological feat. Drs Kar and Bhatt examine the role of direct antagonists to coagulation factor Xa in the secondary prevention of cardiovascular events.
The combination of aspirin plus clopidogrel is the benchmark against which new strategies are compared. Variable pharmacodynamic effects of clopidogrel 6 have prompted the development of new agents. Unfortunately, current pharmacodynamic testing has not demonstrated utility to guide the intensity of antiplatelet therapy 7. While some might conclude that pharmacodynamic testing does not hold clinical utility, an alternative explanation may be that the methods being evaluated are inadequate and new methods must be developed. Optimal individualized therapy will be achieved only after development and validation of assays that accurately reflect the prothrombotic and antithrombotic milieu within each individual.
