Platelet reactivity and pharmacodynamic response to ticagrelor in patients undergoing extracorporeal cardiopulmonary resuscitation compared with conventionally resuscitated cardiac arrest patients

Background Extracorporeal membrane oxygenation (ECMO) induces complex hemostatic disturbances, and the pharmacodynamic response to oral P2Y12 inhibitors during extracorporeal cardiopulmonary resuscitation (ECPR) is poorly characterized. We compared platelet reactivity and ticagrelor response between ECPR and conventionally resuscitated cardiac arrest patients. Methods In this single-center analysis of two prospectively collected, non-contemporaneous cohorts, 16 adults undergoing ECPR and percutaneous coronary intervention (PCI) were compared with 20 conventionally resuscitated cardiac arrest patients undergoing PCI without ECMO. All received crushed ticagrelor via gastric tube. Platelet reactivity was measured before and 2–48 h after loading by Multiplate adenosine diphosphate (ADP) aggregometry and the VerifyNow P2Y12 assay (P2Y12 reaction units, PRU) and analyzed with linear mixed-effects models. Results Baseline PRU was lower in ECPR patients (median 220 vs. 246; p = 0.020), independently of platelet count. After loading, PRU declined more slowly with ECPR (group × time interaction p < 0.001) and was on average 95 PRU higher (95% CI 41–148; p < 0.001; adjusted for baseline and age); median PRU remained above the high on-treatment reactivity threshold for 4 h. Baseline Multiplate aggregation was lower with ECPR (22 vs. 60 U; p = 0.033), but not after adjustment for platelet count, and did not differ after loading. Major bleeding tended to be more frequent with ECPR (43.8% vs. 15.0%; p = 0.073). Conclusions Enteral ticagrelor provides delayed and attenuated P2Y12 inhibition in ECPR patients, despite a bleeding tendency. Multiplate may underestimate this deficit when platelet counts are low. Rapid-onset, reversible intravenous P2Y12 inhibition warrants evaluation.