The Glycoprotein (GP)Ib-IX-V Complex on Platelets: GPIb alpha Protein Expression Is Reduced in HeartMate 3 Patients with Bleeding Complications within the First 3 Months

International journal of molecular sciences(2023)

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摘要
Non-surgical bleeding (NSB) remains the most critical complication in patients under left ventricular assist device (LVAD) support. It is well known that blood exposed to high shear stress results in platelet dysfunction. Compared to patients without NSB, decreased surface expression of platelet receptor GPIb alpha was observed in LVAD patients with NSB. In this study, we aimed to compare the expression level of glycoprotein (GP)Ib-IX-V platelet receptor complex in HeartMate 3 (HM 3) patients with and without bleeding complications to investigate the alterations of the platelet transcriptomic profile on platelet damage and increased bleeding risk. Blood samples were obtained from HM 3 patients with NSB (bleeder group, n = 27) and without NSB (non-bleeder group, n = 55). The bleeder group was further divided into patients with early NSB (bleeder <= 3 mo, n = 19) and patients with late NSB (bleeder > 3 mo, n = 8). The mRNA and protein expression of GPIb alpha, GPIX and GPV were quantified for each patient. Non-bleeder, bleeder <= 3 mo and bleeder > 3 mo were comparable regarding the mRNA expression of GPIb alpha, GPIX and GPV (p > 0.05). The protein analysis revealed a significantly reduced expression level of the main receptor subunit GPIb alpha in bleeders <= 3 mo (p = 0.04). We suggest that the observed reduction of platelet receptor GPIb alpha protein expression in patients who experienced their first bleeding event within 3 months after LVAD implantation may influence platelet physiology. The alterations of functional GPIb alpha potentially reduce the platelet adhesion capacities, which may lead to an impaired hemostatic process and the elevated propensity of bleeding in HM 3 patients.
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关键词
heart failure,ventricular assist device,mechanical circulatory support,non-surgical bleeding,platelet glycoprotein
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