P1623Association of low hemoglobin with venous thromboembolism in acutely ill hospitalized medical patients: findings from the APEX trial

Abstract

Background: Anemia is a common finding and independent predictor for adverse outcomes in hospitalized patients with medical illness. It remains unclear whether anemia is a risk factor for venous thromboembolism (VTE) and whether the presence of anemia can refine risk assessment for prediction of VTE, thereby adding incremental utility to a validated VTE model. Methods: In the APEX trial, 7,513 hospitalized medical patients were randomized to receive either betrixaban or standard-of-care enoxaparin for thromboprophylaxis. Baseline hemoglobin concentrations were obtained in 6,861 patients with a follow-up of 77 days. Symptomatic VTE events, including symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE-related mortality, were compared between low hemoglobin and normal hemoglobin group (normal range: 12.5 to 17.0 g/dL for males and 11.0 to 15.5 g/dL for females). The relationship between anemia and VTE events was assessed by fitting a univariable and multivariable logistic regression model composed of thromboprophylaxis and VTE risk factors. VTE risk refinement by hemoglobin measurement was evaluated in the IMPROVE risk assessment model. Results: Low hemoglobin at baseline was associated with a greater risk of symptomatic VTE (RR=1.94 [95% CI: 1.27-2.98]; p=0.002), symptomatic DVT (RR=2.29 [1.12-4.68]; p=0.019), and non-fatal PE (RR=2.63 [1.22-5.65]; p=0.010) but not VTE-related mortality (RR=1.47 [0.71-3.04]; p=0.30). After adjusting for thromboprophylaxis, history of previous VTE, intensive or coronary unit admission and D-dimer, low hemoglobin (as a categorical or continuous variable) remained associated with an increased likelihood of VTE (adjusted OR=1.71 [1.09-2.69]; p=0.020). Low hemoglobin also improved VTE risk discrimination and reclassification after inclusion in the IMPROVE model. Conclusions: Anemia was independently associated with a greater risk of symptomatic VTE among acutely ill medical patients despite the provision of thromboprophylaxis. Hemoglobin measurement also improved risk stratification by the IMPROVE VTE risk score.