Bleeding events in patients with cancer: incidence, risk factors, and impact on prognosis in a prospective cohort study

• Patients with cancer are at high risk of clinically relevant bleeding, regardless of anticoagulation use.

• The occurrence of clinically relevant bleeding is associated with an increased all-cause mortality.

Hemostatic imbalances are frequent in patients with cancer. While cancer-associated thrombotic complications have been well characterized, data on bleeding events in cancer patients are sparse. Therefore, we aimed to investigate the incidence, risk factors, and impact on prognosis of bleeding events in cancer patients initiating systemic anti-cancer therapies in a prospective cohort study, the Vienna Cancer, Thrombosis and Bleeding Study (CAT-BLED). The primary study outcome was defined as clinically relevant bleeding (CRB), comprising major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). In total, 791 patients (48% female, median age [interquartile range, IQR]: 63 [54-70] years) with various cancer types, 65.5% stage IV, were included. Over a median follow-up of 19 months (IQR: 8.7-24.0), we observed 194 CRB events in 139 (17.6%) patients, of which 42 (30%) were tumor-related, 64 (46.0%) gastrointestinal, and 7 (5.0%) intracerebral. The 12-month cumulative incidence of first CRB and MB was 16.6% (95% confidence interval [CI]: 13.7-19.6) and 9.1% (95% CI: 6.8-11.3) in the whole cohort and 14.4% (95% confidence interval [CI]: 11.2-17.5) and 7.0% (95% CI: 4.7-9.2) in those without anticoagulation. Patients with head and neck cancer had the highest risk of CRB. Lower baseline hemoglobin and albumin were associated with bleeding in patients without anticoagulation. Seven (5.0%) bleeding events were fatal, of which 6 occurred in patients without anticoagulation. Patients with CRB were at an increased risk of all-cause mortality (multivariable transition hazard ratio [95%CI]: 5.80 [4.53-7.43]). In patients with cancer bleeding events represent a frequent complication and are associated with increased mortality.