Venoarterial extracorporeal membrane oxygenation has emerged as a viable treatment for patients in cardiogenic shock with biventricular failure and pulmonary dysfunction. Advances in pump and oxygenator technology, cannulation strategies, patient selection and management, and durable mechanical circulatory support have contributed to expanded utilization of this technology. However, challenges remain that require investigation to improve outcomes.

Introduction: Platelet hyperreactivity associates with cardiovascular events in humans. Studies in mice and humans suggest that prostaglandin E 2 (PGE 2 ) regulates platelet activation. In mice, activation of the PGE 2 receptor subtype 3 (EP3) promotes thrombosis, but the significance of EP3 in humans is less well understood.

Interindividual variation in the ability of aspirin to inhibit platelet cyclooxygenase-1 (COX-1) could account for some on-treatment cardiovascular events. Here, we sought to determine whether there are clinical phenotypes that are associated with a suboptimal pharmacological effect of aspirin. In a prospective, 2-week study, we evaluated the effect of aspirin 81 mg on platelet COX-1 in 135 patients with stable CAD by measuring serum thromboxane B2 (sTxB2) as an indicator of inhibition of platelet COX-1. A nested randomized study compared enteric-coated with immediate-release formulations of aspirin. We found that sTxB2 was systematically higher among the 83 patients with metabolic syndrome than among the 52 patients without (median 4.0 ng/mL vs. 3.02 ng/mL, P=0.013). Twelve (14%) patients with metabolic syndrome, but none without metabolic syndrome, had sTxB2 levels consistent with inadequate inhibition of COX (sTxB2 ≥13 ng/mL). In linear regression models, metabolic syndrome (but none of its individual components) significantly associated with higher levels of log-transformed sTxB2 (P=0.006). Higher levels of sTxB2 associated with greater residual platelet function measured by aggregometry-based methods. Among the randomized subset, sTxB2 levels were systematically higher among patients receiving enteric-coated aspirin. Last, urinary 11-dehydrothromboxane B2 did not correlate with sTxB2, suggesting that the former should not be used to quantitate aspirin’s pharmacological effect on platelets. In conclusion, metabolic syndrome, which places patients at high risk for thrombotic cardiovascular events, strongly and uniquely associates with less effective inhibition of platelet COX-1 by aspirin.

The platelet thrombus is the major pathologic entity in acute coronary syndromes, and antiplatelet agents are a mainstay of therapy. However, individual patient responsiveness to current antiplatelet drugs is variable, and all drugs carry a risk of bleeding. An understanding of the complex role of Prostaglandin E2 (PGE2) in regulating thrombosis offers opportunities for the development of novel individualized antiplatelet treatment. However, deciphering the platelet regulatory function of PGE2 has long been confounded by non-standardized experimental conditions, extrapolation of murine data to humans, and phenotypic differences in PGE2 response. This review synthesizes past and current knowledge about PGE2 effects on platelet biology, presents a rationale for standardization of experimental protocols, and provides insight into a molecular mechanism by which PGE2-activated pathways could be targeted for new personalized antiplatelet therapy to inhibit pathologic thrombosis without affecting hemostasis.

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