Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients.

Essentials Neutrophil extracellular traps (NETs) might play a role in cancer-related coagulopathy. We determined NET biomarkers and followed cancer patients for venous thromboembolism (VTE). We found a constant association with VTE for citrullinated histone H3. Biomarkers of NET formation could reflect a novel pathomechanism of cancer-related VTE. SUMMARY: Background Neutrophil extracellular traps (NETs) are decondensed chromatin fibers that might play a role in the prothrombotic state of cancer patients. Objectives To investigate whether the levels of citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell-free DNA (cfDNA) and nucleosomes predict venous thromboembolism (VTE) in cancer patients. Patients/Methods Nine-hundred and forty-six patients with newly diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study. H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients were followed for 2 years. VTE occurred in 89 patients; the cumulative 3-month, 6-month, 12-month and 24-month incidence rates of VTE were 3.7%, 6.0%, 8.1%, and 10.0%, respectively. Results Patients with elevated H3Cit levels (> 75th percentile of its distribution, n = 236) experienced a higher cumulative incidence of VTE (2-year risk of 14.5%) than patients with levels below this cut-off (2-year risk of 8.5%, n = 710). In a competing-risk regression analysis, a 100 ng mL-1 increase in H3Cit level was associated with a 13% relative increase in VTE risk (subdistribution hazard ratio [SHR] 1.13, 95% confidence interval [CI] 1.04-1.22). This association remained after adjustment for high VTE risk and very high VTE risk tumor sites, D-dimer level, and soluble P-selectin level (SHR 1.13, 95% CI 1.04-1.22). The association of elevated nucleosome and cfDNA levels with VTE risk was time-dependent, with associations with a higher risk of VTE only during the first 3-6 months. Conclusion These data suggest that biomarkers of NET formation are associated with the occurrence of VTE in cancer patients, indicating a role of NETs in the pathogenesis of cancer-associated thrombosis.

PO-01 - Congestive heart failure is an independent risk factor for venous thromboembolism and mortality in cancer patients.

INTRODUCTION: Prediction of venous thromboembolism (VTE) occurrence in cancer patients using individual risk factors may contribute to preventing the burden of disease associated with VTE. Congestive heart failure in patients with cancer may increase the risk of VTE and worsen the prognosis. AIM: We sought to investigate the association of congestive heart failure and occurrence of VTE in cancer patients, specifically with consideration for the poor prognosis in patients with heart failure and cancer. MATERIALS AND METHODS: Hospitalized and ambulatory cancer patients were included in the prospective Vienna Cancer and Thrombosis Study (CATS) in search of risk factors for occurrence of VTE. Cancer entities and comorbidities were recorded at baseline and verified using medical documentation including a diagnosis of congestive heart failure. The occurrence of VTE events was compiled via mail and telephone follow-ups for two years. Risk of VTE occurrence was calculated in the competing risk regression model, considering death as a competing event during follow-up. RESULTS: In the current analysis 1,433 patients (632 women, 44.1%) with a median age of 61 years (25th-75th percentile: 52-75) were included. During the observation period, 108 (7.5%) VTE events and 522 (36.4%) deaths occurred. The median observation time was 729 days (233-731), and 34 patients (2.3%) had diagnosed congestive heart failure at the time of study inclusion, 12 of which had NYHA II-IV and 22 unspecified congestive heart failure. In the group of heart failure patients, 6 had VTE events and 23 died. In univariate competing risk analysis, the risk of VTE occurrence was increased 2.6-fold in patients with heart failure compared to those without a diagnosis of heart failure (SHR 2.58, 95% CI 1.13-5.92, p=0.025). After multivariable adjustment for age, BMI, gender, diabetes, history of myocardial infarction or stroke, use of antiplatelet drugs, cancer site, hypertension, D-Dimer level and peripheral arterial disease, the risk of VTE in heart failure patients was 3-times the risk of patients without heart failure (HR 3.07, 95% CI 1.15-8.19, p=0.025). Further, congestive heart failure was a strong predictor of mortality (HR 1.70, 95% CI 1.10-2.65, p=0.018). CONCLUSIONS: Congestive heart failure is not only a risk factor for mortality in cancer patients, but also an independent predictor of VTE occurrence. In order to prevent VTE and the associated burden, patients with cancer and congestive heart failure may benefit from thromboprophylaxis.