Association of erythropoiesis-stimulating agents and red blood cell transfusion with venous thrombosis in patients with cancer: a nationwide case-crossover study.

BACKGROUND

Cancer-associated anemia is commonly managed with erythropoiesis-stimulating agents (ESAs) and red blood cell (RBC) transfusions; however, their relative thrombotic risks remain uncertain.

METHODS

We conducted a nationwide population-based case-crossover study using the Korean National Health Insurance Database. Adult patients with newly diagnosed cancer between 2011 and 2020 who developed incident venous thrombosis were included. Exposure to ESAs and other time-varying risk factors was assessed during a 12-week hazard period preceding thrombosis and compared with a matched 12-week control period, separated by a 24-week washout interval. Conditional logistic regression was used to estimate odds ratios (ORs).

RESULTS

Among 710,910 patients with cancer, several clinical exposures occurred more frequently during the hazard period than during the control period, including RBC transfusion (6.85% vs 1.79%), hospitalization (11.79% vs 2.77%), surgery (5.70% vs 2.00%), and central venous catheter insertion (3.34% vs 0.74%) (all p < .001). In unadjusted analyses, both ESA use (OR, 3.14; 95% CI, 2.63-7.75) and RBC transfusion (OR, 3.83; 95% CI, 3.58-4.11) were associated with an increased risk of venous thrombosis. After adjustment for time-varying confounders, ESA use was not significantly associated with thrombosis (adjusted OR, 1.12; 95% CI, 0.93-1.36), whereas RBC transfusion remained independently associated with an increased risk (adjusted OR, 1.44; 95% CI, 1.32-1.58). Sensitivity analyses using 8-week and 4-week exposure windows showed consistent results.

CONCLUSIONS

RBC transfusion was associated with an increased risk of venous thrombosis in patients with cancer, whereas ESA therapy was not independently associated with thrombotic complications after adjustment. These findings suggest that RBC transfusion may contribute to thrombotic risk in patients with cancer and highlight the need for careful consideration when managing cancer-associated anaemia.