The study will be conducted in a single high-volume LVAD implantation center. The clinical study is a prospective clinical investigation.
Studies showed that in patients after LVAD implantation with the acquired von Willebrand syndrome and prior gastrointestinal bleeding, there is a seven-fold risk of thromboembolic complications. We hypothesize that in LVAD patients, fibrinolysis could be disturbed in a similar mechanism. In patients with aortic stenosis, the severity of stenosis is correlated with oxidative stress and impaired fibrinolysis. It is possible that the von Willebrand factor binds to platelets due to oxidative stress. In severe aortic stenosis, non-pulsatile systemic flow and increased shear stress cause the development of angiodysplasia and the acquired von Willebrand syndrome with gastrointestinal bleeding (Heyde syndrome). The mechanism is similar as in severe aortic stenosis. One observational study showed that platelet-thrombus formation in LVAD patients was significantly impaired due to this condition. As a result, the altered structure of the von Willebrand factor leads to its cleavage by metalloprotease ADAMTS-13. Increased shear stress leads to a mechanical destruction of large von Willebrand multimers.
The acquired von Willebrand syndrome is a well-known phenomenon in patients treated with CF-LVAD, which leads to more frequent bleeding incidents. Adverse outcomes were defined as bleeding events (bleeding in general or in the following subtypes: severe bleeding, fatal bleeding, gastrointestinal bleeding, intracranial bleeding), thromboembolic events (stroke or transient ischemic attack, pump thrombosis, including thrombosis within the pump or its inflow or outflow conduits, arterial peripheral thromboembolism), and death. We plan to assess the hemostasis system at four different time points, i.e., before LVAD implantation, 3–4 months after LVAD implantation, 6–12 months after LVAD implantation, and at the end of the study (at 5 years or at the time of the adverse event). Therefore, we plan to investigate 90 consecutive left ventricular assist device (LVAD) patients and study in vitro fibrin clot properties (clot lysis time, clot permeability, fibrin ultrastructure using a scanning electron microscope) and the calibrated automated thrombogram in addition to the von Willebrand factor antigen, fibrinogen, D-dimer, prothrombin time/international normalized ratio (PT/INR), and activated partial thromboplastin time (APTT) to identify prognostic factors of adverse outcomes during the course of therapy. Little is known about prognostic factors determining these adverse events in this group of patients. Despite advancing technologies, bleeding and thromboembolic events strongly decrease the survival and the quality of life of these patients. Left ventricular assist devices are a treatment option for end-stage heart failure patients.
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