The Association Between Anemia and Bleeding in Thrombocytopenic Patients with a Hematological Malignancy

Introduction/Objective Patients with hematological malignancies who are receiving chemotherapy have a heightened risk of bleeding because of the presence of both anemia and thrombocytopenia. The objective of this study was to determine the association between severe anemia, defined as hemoglobin (Hb) < 70 g/L in the three days before the first major bleeding event, and the risk of major bleeding in patients with hematological malignancy. A major bleed was defined as Grade 2 or higher on the World Health Organization (WHO) scale. Design and Methods We did a substudy of patients from the PREPAReS trial, a randomized trial comparing the efficacy of pathogen-inactivated platelets versus untreated platelet products in patients with hematological malignancy undergoing chemotherapy treatment. Daily hemoglobin levels, platelet counts, and WHO-graded bleeding assessments were collected during the trial. Cox regression analysis was used to assess the effect of anemia on risk of the first major bleed. Anemia was defined as a daily binary covariate of lowest Hb < 70 g/L or >/=70 g/L in the past three days. Cox regression models were adjusted for potential risk factors including sex, age, diagnosis (acute myeloid leukemia [AML] or non-AML), country, treatment stage, and study randomization arm. The substudy was approved by the research ethics board. Results 565 patients were included from ten centres in three countries. 270 patients had AML (47.8%) and 182 patients were female (32.2%). In total, 321 patients (56.8%) developed a bleed of Grade 2 or higher. The first bleeding events were Grade 2 (n=309; 96.3%), Grade 3 (n=4; 1.2%) or Grade 4 (n= 8; 2.5%). A significant association between Hb < 70 and risk of bleeding was observed (Hazard ratio=1.71, p=0.009). Females had a higher risk of bleeding during the first seven days from randomization compared to males (HR=2.28, p< 0.001). Five (0.9%) females had vaginal-related bleeding. Difference in risk of major bleeding was observed between countries (p< 0.05). Conclusions Severe anemia was associated with major bleeding in patients with hematological malignancy undergoing chemotherapy. Maintaining a higher hemoglobin level for this patient group should be considered and evaluated in prospective trials.