Altered clot formation and fibrinolysis in heart transplant recipients

Abstract Background Long-term survival after heart transplantation (HTx) is limited by cardiac allograft vasculopathy (CAV), a frequent accelerated form of coronary artery disease. The pathogenesis remains incompletely understood, but thrombosis may be involved. We aimed to investigate clot formation and fibrinolysis in HTx patients and relate the findings to prognosis. Methods This prospective cohort study included 69 patients (median 8.4 years after HTx) with angiographically documented CAV 0 (not significant, n=36), CAV 1 (mild, n=19), and CAV 2-3 (moderate to severe, n=14). Healthy individuals (n=69) served as age- and gender-matched controls. Using a plasma-based fibrin clot formation and lysis assay, we assessed the following clot properties off-aspirin: 1) clot formation reflected by peak absorbance, 2) fibrinolysis measured by clot lysis time, and 3) a combined measure of clot formation and lysis reflected by area under the curve (AUC). Major adverse cardiac events (MACE) included heart failure hospitalization, cardiovascular death, and significant CAV progression. Results Median follow-up time was 5.1 (2.1-5.9) years. Five CAV 2-3 patients were excluded as it was not considered safe to interrupt aspirin therapy. Five patients had missing values due to either lysis resistance or severely decreased fibrin formation, and four of these underwent MACE with CAV progression and/or heart failure during follow up. Peak absorbance was significantly higher in HTx patients compared with healthy controls (0.72 vs. 0.50 aggregation units (AU), p<0.0001). Further, a stepwise increment above reference range through CAV groups was seen; CAV 2-3 patients (0.85 ± 0.12 AU) versus CAV 1 patients (0.72 ± 0.17 AU, p<0.05) and CAV 0 patients (0.68 ± 0.27 AU, p=0.06). Clot lysis time was significantly longer in HTx patients compared with healthy controls (1275 vs. 733 seconds, p<0.0001). AUC was significantly increased compared with healthy controls (1399 vs. 547 AU x seconds, p<0.0001). Overall, clot formation and fibrinolysis was not related to MACE. Conclusion HTx-patients have increased clot formation and prolonged fibrinolysis compared with healthy controls. Further, HTx-patients have an increased combined measure of these parameters compared with healthy controls, suggesting imbalance between fibrin clot formation and fibrinolysis. None of the measured parameters were related to prognosis.Clot formation and fibrinolysis