Abstract 532: Shear-induced Release of Platelet Receptors Contributes to Bleeding Outcomes in Patients With Lvads or Exposed to Ecmo

Abstract

Despite advances in design and materials, as well as pharmacological prophylaxis, hemostatic complications continue to plague device recipients. Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) are associated with bleeding that is not fully explained by anticoagulant or antiplatelet use. Exposure of platelets to elevated shear in vitro leads to increased shedding. We examined blood samples from patients with heart failure or in receipt of high fluid shear mechanocirculatory support to assess whether loss of platelet receptors occurs in vivo , and the relationship with acquired von Willebrand syndrome (AVWS) and changes in inflammatory cytokines. Platelet counts, levels of inflammatory cytokines IL-1β, IL-6, TNFα, MCP-1, IL-17A and IFNγ, coagulation tests and von Willebrand factor (VWF) analyses were performed on samples from 13 continuous flow VAD (CF-VAD), 14 ECMO, and 24 heart failure patients. Levels of platelet receptors were measured by flow cytometry or ELISA. The loss of high molecular weight VWF multimers was observed in 12 of 13 CF-VAD and 7 of 14 ECMO patients, consistent with AVWS. Platelet receptor shedding was demonstrated by elevated soluble glycoprotein (GP) VI levels in plasma and significantly reduced surface GPIbα and GPVI levels in CF-VAD and ECMO patients as compared with healthy donors. Platelet receptor levels were also significantly reduced in heart failure patients. Significant differences in levels of inflammatory cytokines monocyte-chemoattractant protein and tissue necrosis factor-a in a subset of patients with decompensated HF. These data link AVWS and increased platelet receptor shedding in patients with CFVADs or ECMO. Loss of the platelet surface receptors GPIbα and GPVI in heart failure, CFVAD and ECMO patients may be linked with extent of inflammation and may contribute to ablated platelet adhesion/activation, and limit thrombus formation under high/pathologic shear conditions.