Left Ventricular Assist Device-Associated Carbon Monoxide and Iron-Enhanced Hypercoagulation: Impact of Concurrent Disease

摘要

Left ventricular assist device (LVAD) therapy is associated with thrombophilia despite anticoagulation. Of interest, LVAD patients have increased carboxyhemoglobin, a measure of upregulated heme oxygenase (Hmox) activity that releases carbon monoxide (CO) and iron. Given that CO and iron enhance plasmatic coagulation, we determined if LVAD patients had hypercoagulability and decreased fibrinolytic vulnerability with measurable CO and iron-mediated effects. Blood samples were obtained a month or more after implantation of the LVAD. Thrombelastographic methods to assess coagulation kinetics, fibrinolytic kinetics, formation of carboxyhemefibrinogen, and iron-mediated enhancement of clot growth were utilized. Coagulation and fibrinolytic parameter normal individual (n = 30) plasma values were determined. Sixteen LVAD patients were studied. CO and iron enhancement of coagulation were observed in the majority of LVAD patients, contributing to hypercoagulation. However, most patients demonstrated abnormally increased rates of clot lysis. Critically, hemolysis as assessed by circulating lactate dehydrogenase activity was small in this cohort, and only four patients without comorbid states (e.g., obesity, diabetes, sleep apnea) were hypercoagulable with evidence of Hmox upregulation. However, seven patients with comorbidities were hypercoagulable with Hmox upregulation. Future investigation of CO and iron-related thrombophilia and comorbid disease is warranted to define its role in LVAD-related thrombosis.