Platelet p1^A2 polymorphism enhances risk of neurocognitive decline after cardiopulmonary bypass

Background. Neurocognitive decline, often produced by atherosclerotic plaque embolization, remains a frequent complication of cardiopulmonary bypass. Plaque fragments may initiate local thrombosis, which, in turn, aggravates the embolic insult. Prothrombotic genetic factors may exacerbate this process. We investigated whether the P1^A2 polymorphism of platelet GPIIIa, a prothrombotic risk factor in other cardiovascular settings, is associated with early neurocognitive decline after cardiopulmonary bypass. Methods. Neurocognitive changes were evaluated by the Mini-Mental State Examination administered preoperatively and on postoperative day 4 and the P1^A geno-type determined in 70 patients undergoing cardiopulmonary bypass. Results. Forty-nine patients were P1^A1/A1, and 21 were P1^A1/A2 or P1^A2/A2. Fifty-two patients (74%) demonstrated post-cardiopulmonary bypass neurocognitive decline, of which 34 were P1^A1/A1 and 18 were P1^A1/A2 or p1^A2/A2. Multivariate analysis revealed that the P1^A2 genotype and baseline Mini-Mental State Examination were significantly associated with greater neurocognitive decline (decreased Mini-Mental State Examination scores, p = 0.036 and 0.024, respectively). Conclusions. This study demonstrates a link between the P1^A2 allele of platelet GPIIIa and more severe neurocognitive decline after cardiopulmonary bypass. Although the mechanism is unknown, it could represent exacerbation of platelet-dependent thrombotic processes associated with plaque embolism.