Glucocorticoids impair platelet thromboxane biosynthesis in community-acquired pneumonia

Previous reports suggest that community-acquired pneumonia (CAP) is associated with an enhanced risk of myocardial infarction (MI) and that enhanced platelet activation may play a role. Aims of this study were to investigate if urinary excretion of 11-dehydro-thromboxane (Tx) B2, a reliable marker of platelet activation in vivo, was elevated in CAP and whether glucocorticoid administration reduced platelet activation. Three-hundred patients hospitalized for CAP were recruited and followed-up until discharge. Within the first 2 days from admission, urinary 11-dehydro-TxB2and serum levels of methylprednisolone and betamethasone were measured. 11-Dehydro-TxB2was also measured in a control group of 150 outpatients, matched for age, sex, and comorbidities. Finally, in-vitro studies were performed to assess if glucocorticoids affected platelet activation, at the same range of concentration found in the peripheral circulation of CAP patients treated with glucocorticoids. Compared to controls, CAP patients showed significantly higher levels of 11-dehydro-TxB2(110 [69-151] vs. 163 [130-225] pg/mg creatinine; p < 0.001). During the in-hospital stay, 31 patients experienced MI (10%). A COX regression analysis showed that 11-dehydro-TxB2independently predicted MI (p = .005). CAP patients treated with glucocorticoids showed significantly lower levels of 11-dehydro-TxB2compared to untreated ones (147 [120-201] vs. 176 [143-250] pg/mg creatinine; p < 0.001). In vitro, glucocorticoids-treated platelets showed a dose-dependent decrease of ADP-induced platelet aggregation, TxB2production, cPLA2phosphorylation and arachidonic acid release from the platelet membrane. In conclusion, platelet TxB2is overproduced in CAP patients and may be implicated in MI occurrence. Glucocorticoids reduce platelet release of TxB2in vitro and urinary excretion of 11-dehydro-TxB2in vivo and may be a novel tool to decrease platelet activation in this setting.