Protein C Pathway, Inflammation, and Pump Thrombosis in Patients With Left Ventricular Assist Devices

Abstract

Use of left ventricular assist devices (LVADs) for management of advanced heart failure is becoming increasingly common; however, device associated thrombosis remains an important cause of mortality in this patient population. We hypothesize that inflammation in LVAD implanted patients dysregulates the protein C pathway, creating a hypercoagulable state leading to thrombosis. Plasma samples from 22 patients implanted with the Thoratec HeartMate II LVAD were analyzed by commercial ELISAs. Retrospective sample selection included those collected 1-3 months prior to and within 1 month after a thrombotic or bleeding event. Unrelated to warfarin dosing, total protein S and free protein S (p = 0.033) levels were 20% lower in patients with LVAD-thrombosis than in patients with LVAD-bleeding. Levels of protein C, soluble endothelial cell protein C receptor, and soluble thrombomodulin were similar in both groups before and after the event. Compared to normal, C-reactive protein levels were 25-fold elevated in LVAD-thrombosis patients but only 9-fold elevated in LVAD-bleeding patients. This study suggests that protein S, influenced by the inflammatory state, is a gatekeeper for the function of protein C in patients with LVAD-associated thrombosis.