The 'A2'allele of the platelet specific alloantigen system is encoded by rs5918 (C), and it has been implicated as increasing the risk of myocardial infarctions, heart disease, and resistance to blood-thinning benefits of aspirin.

It has been hypothesized that the clinical efficacy of antiplatelet drugs (e.g., aspirin) may be related to PLA2 polymorphism. In PLA2 carriers, it has been reported the inhibition of the altered thrombin generation by low-dose aspirin and a shorter bleeding time before and after receiving 300 mg of aspirin. In contrast, Cooke et al. found weaker PLA2 platelet aggregation in response to aspirin in vitro.

In the study it was showed that the PLA2 allele presence is associated with enhanced thrombin formation and therefore faster activation of factor V, factor XIII, and fibrinogen cleavage. In addition, PLA2 carriers exhibit an impaired anticoagulant action of aspirin.

The time of initial bleeding was lower in carriers of PLA2 than in PLA1A1 homozygotes (307 ± 18 versus 345 ± 19 seconds; P = 0.046). Aspirin (75 mg/dl) prolonged bleeding time in 52 ± 6 (P = 0.032) and 122 ± 8 seconds (P = 0.002), respectively; the difference was significant after treatment (P = 0.003). No differences were observed for genotype or aspirin concentration in the first 30 seconds interval.

The main action mode of aspirin includes the inhibition of thromboxane A2 production by acetylation of platelet cyclooxygenase. Aspirin decreased thrombin generation in vitro and in vivo. Current and previous studies show that, unlike the PLA1A1 homozygous, thrombin formation in the lesion site is not affected by the low dose aspirin in healthy PLA2 carriers. Curiously, aspirin increases the differences in blood coagulation observed among PLA2 subjects (positive and negative). It was also found that platelets from heterozygous PLA1A2, in contrast to PLA2A2 homozygotes were more sensitive for 2.5 and 5 mmol/L Aspirin. These in vitro observations seem to differ from the results in vivo.

This study demonstrated that thrombin is generated more rapidly in sites of microvascular injury in PLA2 carriers, compared to PLA1A1 homozygous, and the difference between genotypes becomes more pronounced with the use of Aspirin. Therefore, PLA2 polymorphism may result in prolongation of procoagulant effects. Because thrombin stimulates the migration of smooth muscle cells and other atherogenic processes, PLA2 polymorphism can also promote atherosclerosis through indirect action, and not by thrombotic action.

These observations could also have relevant therapeutic implications, as the antithrombotic effects of Aspirin may be decreased in PLA2 carriers.

In summary, the rs5918 (C) allele carriers showed resistance to aspirin at anticoagulants doses and an increased risk of forming thrombi.

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