(652) - LVAD Support Increases Plasma Iron Species: Implications for a Pathophysiologic Relationship between LVAD-Associated Hemolysis and Thrombosis

Abstract

Emerging evidence suggests a relationship between left ventricular assist device (LVAD)-associated hemolysis and LVAD thrombosis. Plasma iron species such as free hemoglobin, hemin, and free iron (Fe2+, Fe3+), which are produced during hemolysis, generate oxidative stress and may promote thrombogenesis. As a preliminary study to guide in vitro mechanistic investigations into contributors to LVAD thrombosis, we examined plasma iron species in patients during LVAD support. Patients undergoing continuous-flow LVAD support were studied (n=23). Whole blood was obtained prior to LVAD implantation and after one week of LVAD support. Lactate dehydrogenase (LDH) was measured as a marker of hemolysis. Free hemoglobin, hemin, Fe2+, and Fe3+ were measured as plasma iron species. Paired Student’s t-tests were performed between pre-LVAD and post-LVAD samples. LVAD support increased LDH (pre-LVAD 245±20 units/L vs. post-LVAD 333±36 units/L, p=0.07), plasma free hemoglobin (pre-LVAD 46±6 mg/dL vs. post-LVAD 67±9 mg/dL, p=0.01), hemin (pre-LVAD 0.26±0.06 μg/dL vs. post-LVAD 4.8±2.3 μg/dL, p=0.06), Fe2+ (pre-LVAD 173±17 μg/dL vs. post-LVAD 220±27 μg/dL, p=0.02), and Fe3+ (pre-LVAD 29±7 μg/dL vs. post-LVAD 51±9 μg/dL, p=0.03). LVAD support significantly increased plasma levels of free hemoglobin, hemin, Fe2+, and Fe3+. Elevated plasma iron species during LVAD support may contribute to the pathophysiology of LVAD thrombosis. These data are guiding in vitro studies to determine whether the relationship between LVAD-associated hemolysis and thrombosis is causal or associative.