Abstract Number: PB1404
Meeting: ISTH 2020 Congress
Background: Enhanced thromboxane (TX)-dependent platelet activation plays a pivotal role in atherothrombosis and type 2 diabetes mellitus (T2DM). Incomplete suppression by low-dose aspirin (ASA) of TX metabolite excretion (urinary 11-dehydro-TXB2) is predictive of cardiovascular (CV) events in high-risk patients. Accelerated platelet turnover is one of the main determinants of the interindividual variability in ASA response, as reflected by accelerated platelet cyclooxygenase (COX-1) recovery during the 24-h dosing interval. Myeloid-related protein (MRP)-8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, known to regulate inflammation and to predict CV events. Under hyperglycemic conditions, MRP 8/14 induces thrombopoietin (TPO) production and thrombocytosis.
Aims: To assess whether MRP8/14 may contribute to interindividual variability in response to low dose ASA in T2DM.
Methods: We enrolled 100 patients, in chronic treatment with ASA (100 mg day) for CV prevention. The kinetics of platelet COX-1 recovery was characterized by measuring serum TXB2 after 10 (the nadir of ASA effect on TXB2) and 24 hours after a witnessed ASA administration. The population was stratified into tertiles, based on the serum TXB2 recovery slope. The third tertile indicated an incomplete suppression of COX-1 activity. Plasma MRP 8/14 was measured by enzyme-linked immunosorbent assays (ELISA).
Results: The levels of U-11-dehydro-TXB2 and MRP 8/14 were higher in the third tertile versus first tertile of the sTXB2 slope (p=0.0497 and p=0.0336) (figure, panel A and B); MRP 8/14 correlated with C-reactive protein (CRP) (rho=0.610, p< 0.001), white blood cells (rho= 0.460, p< 0.001), U-11-dehydro-TXB2(rho=0.264, p=0.035) and with thrombopoietin (TPO) (rho= 0.253, p=0.047) (Figure, panel C and D).
Conclusions: Enhanced circulating MRP 8/14 in the setting of low grade inflammation may stimulate TPO production from hepatocyte driving megakaryopoiesis, thus contributing to suboptimal response to ASA and residual TX-dependent platelet activation.
To cite this abstract in AMA style:Simeone PGM, Tripaldi R, Liani R, Ciotti S, Boccatonda A, D'Ardes D, Santilli F. Circulating Myeloid-related Protein (MRP)-8/14 May Contribute to Suboptimal Response to Low Dose Aspirin in Patients with Type 2 Diabetes mellitus [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/circulating-myeloid-related-protein-mrp-8-14-may-contribute-to-suboptimal-response-to-low-dose-aspirin-in-patients-with-type-2-diabetes-mellitus/. Accessed November 29, 2023.
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