Venous thromboembolism and bleeding in cancer patients: role of inflammatory and cardiac biomarkers

Abstract Background and Aims Patients with cancer have increased risk of venous thromboembolism (VTE) and bleeding. Inflammatory and cardiac biomarkers may predict these complications, but their role remains unclear. This study examined associations between two inflammatory-related markers (C-reactive protein and growth differentiation factor-15) and two cardiac markers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-TnT) with VTE and clinically relevant bleeding in cancer patients. Methods A post hoc analysis of the AVERT trial, which evaluated apixaban for VTE prevention in ambulatory cancer patients with a Khorana score of ≥2, was performed. Biomarkers were measured at baseline and 1 month, with C-reactive protein also at 3 months. Fine and Gray regression, accounting for competing risk of death and adjusted for age and advanced cancer, estimated subdistribution hazard ratios (SHRs) for VTE and clinically relevant bleeding. Results Of 574 patients, 514 provided baseline samples. One- and 3-month samples were available from 454 and 447, and 378 and 364, patients without prior VTE and bleeding events, respectively. Elevated baseline growth differentiation factor-15 was associated with increased VTE risk SHR 1.36, 95% confidence interval (CI) 1.01–1.84. N-terminal pro-B-type natriuretic peptide (SHR 1.44, 95% CI 1.08–1.92) and C-reactive protein (SHR 1.38, 95% CI 1.07–1.76) were linked to bleeding risk. Increasing high-sensitivity troponin T from baseline to 1 month was associated with higher VTE risk (SHR 1.89, 95% CI 1.14–3.16). Nomograms were developed to estimate VTE and clinically relevant bleeding risks. Conclusions Select inflammatory-related and cardiac markers were associated with VTE and bleeding risks in cancer patients, which can be determined using developed nomograms. Prospective research is needed to confirm these findings.