Activated Immune Response in Ventricular Assist Device Implanted Patients Identified through a Platelet Activation Biomarker

• Published in: Blood 2016-12, Vol.128 (22), p.5001-5001
• Main Authors: Jeske, Walter, Walenga, Jeanine M., Torres, Tania, Escalante, Vicki, Schwartz, Jeffrey, Bakhos, Mamdouh
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.5001.5001

Introduction: Mechanical circulatory support using an implanted ventricular assist device (VAD) is an important means of enhancing or maintaining the quality of life for heart failure patients awaiting heart transplant (bridge to transplant), during the recovery of their own heart (bridge to recovery) or for long-term destination therapy (no transplant). The non-physiologic continuous blood flow of a VAD (CF-VAD) exposes blood and vasculature to abnormal shear stress and leads to a variety of hemostatic derangements that likely contribute to the development of bleeding complications, neurologic dysfunction and venous thromboembolism in these patients. Additionally, the implanted CF-VAD likely stimulates the body's natural innate immune response to a foreign object. We hypothesize that the continuous activation of platelets due to the non-physiologic blood flow and the foreign nature of the CF-VAD combine to stimulate an immune response. Previous studies have suggested thatanti-PF4/heparin antibodies [as targeted in a diagnosis of heparin-induced thrombocytopenia (HIT)] can develop in the absence of heparin. It is believed that these antibodies are not related to heparin per se but rather are generated as a physiological response by platelets, in their capacity to generate an innate immune response, reacting to non-self substances. This study evaluated the time course of anti-PF4/heparin titers in patients supported by CF-VADs. Methods: Blood samples were collected from 13 randomly selected patients prior to implantation of a HeartMate II CF-VAD and at routine clinic visits following implantation. Median follow-up was 183 days (range: 32-352 days). Anti-PF4/heparin antibody titers were determined by the PF4 Enhanced X-45 Assay (Immucor GTI Diagnostics, Waukesha, WI). Patients were treated with heparin at the time of implant; long-term anticoagulation was maintained with warfarin (INR 1.5-2.0) and low-dose aspirin. Results: Following CF-VAD implantation, there was an acute increase in median platelet count from 169,000 to 420,000/µl. With increasing time post-implant, the median platelet count returned to pre-implant levels; no patients became thrombocytopenic. Pre-implant, 6 of 13 patients had ’positive’ anti-PF4/heparin titers (OD >0.4 using the HIT criteria); the median OD for all patients was 0.433. There was a progressive increase in median titer with increasing time post-implant. At 1 month the median OD was 0.54. By 2 months all patients had an OD >0.