Risk Factors Associated with Bleeding After Alteplase Administration for Pulmonary Embolism: A Case-Control Study

STUDY OBJECTIVE To identify risk factors associated with bleeding in patients who received alteplase for pulmonary embolism (PE), with a specific focus on risk factors available to the clinician at the time thrombolytics are being considered. DESIGN Case-control study. SETTING Large academic medical center. PATIENTS Sixty-two adults with PE who were administered alteplase 100 mg over a 2-hour infusion period between January 2000 and October 2011; of these patients, 28 experienced major bleeding (case patients), and 34 did not develop major bleeding (control patients). MEASUREMENTS AND MAIN RESULTS Risk factors for bleeding from alteplase were compiled from the U.S. product label and the literature. Multivariate logistic regression analysis was used to assess for risk factors independently associated with bleeding. Patients with major bleeding more frequently had recent major surgery (odds ratio [OR] 9.00, 95% confidence interval [CI] 1.01-79.99, p=0.039), an international normalized ratio above 1.7 (OR 13.20, 95% CI 1.54-113.52, p=0.008), and one or more risk factors for bleeding (OR 5.02, 95% CI 1.68-15.04, p=0.003). On multivariate analysis, one or more risk factors for bleeding (adjusted OR 5.74, 95% CI 1.78-18.55, p=0.004) and body weight (adjusted OR 1.18 for each 10 kg below 100 kg, 95% CI 1.01-1.37, p=0.035) were independently associated with major bleeding. Intensive care unit length of stay after alteplase administration was significantly longer in patients with major bleeding (median 2.2, interquartile range [IQR] 0.9-4.8) days versus 1.1 (IQR 0.4-1.9 days, p=0.028). CONCLUSION Risk factors for bleeding that are available to clinicians at the time the decision is made to administer alteplase for PE are significantly associated with the occurrence of major bleeding; the odds of major bleeding in patients with one or more risk factors for bleeding were similar to 5 times higher than in patients without these risk factors. Thus clinicians should weigh these risk factors for bleeding against the perceived benefit of thrombolytic therapy when deciding to administer a thrombolytic in an individual patient with PE.