Growth Differentiation Factor-15 Predicts Major Bleeding in Cancer Patients

Abstract

Background

The hemostatic system is tightly interconnected with cancer. Research has focused predominantly on thrombotic complications, but less is known about bleeding and bleeding risk prediction. Growth differentiation factor (GDF)-15 has previously emerged as a prognostic biomarker for bleeding.

Objectives

The aim of this study was to investigate the association and predictive ability of GDF-15 for bleeding risk in patients with cancer.

Methods

The CAT-BLED (Vienna Cancer, Thrombosis, and Bleeding) study is a prospective, observational cohort study including cancer patients initiating systemic anticancer therapies. Patients were followed for up to 2 years for thrombotic and bleeding events. The primary outcome was major bleeding. GDF-15 was measured at inclusion and at 3 and 6 months of follow-up.

Results

A total of 779 patients (48% women, median age 62 years, 15% on therapeutic anticoagulation) were included. During a median follow-up period of 18 months, 79 patients (10.1%) experienced major bleeding (12-month cumulative incidence 8.8%; 95% CI: 6.7-10.9). Higher GDF-15 levels were independently associated with increased major bleeding risk (adjusted subdistribution HR per doubling: 1.29; 95% CI: 1.04-1.59), and patients with levels greater than the cohort median (1,864 ng/L) had a significantly higher 12-month cumulative incidence (13.1% vs 4.6%; P < 0.001). This association remained robust in follow-up measurements at 3 and 6 months. GDF-15 showed moderate to good discrimination for predicting 6-month major bleeding risk (C statistic = 0.69; 95% CI: 0.60-0.77). GDF-15 was not associated with venous thromboembolism but was strongly associated with mortality (adjusted HR: 1.37; 95% CI: 1.25-1.50).

Conclusions

GDF-15 levels predict major bleeding risk in cancer patients and are not associated with venous thromboembolism, making GDF-15 a particularly promising biomarker for bleeding risk prediction.