A Multicenter Evaluation of the Safety of Drotrecogin Alfa (Activated) in Patients with Baseline Bleeding Precautions

Purpose: We recently reported an increased incidence of serious bleeding events and mortality in patients with baseline bleeding precautions treated with drotrecogin alfa (activated) compared to patients without such precautions. Whether these observations were specific to our single medical campus is unclear. Methods: All patients who received drotrecogin alfa (activated) for the treatment of severe sepsis from January 2006 through September 2009 within the South Central Veterans Affairs Health Care Network were retrospectively reviewed using a regional clinical database. Demographic information, bleeding precautions that were exclusion criteria of the PROWESS trial, and 30-day post-discharge incidences of serious bleeding events and mortality were collected. Results: Seventy-nine patients from 5 medical centers were included. Serious bleeding events occurred in 4 of 24 patients (16.7%) with any bleeding precaution vs 1 of 55 patients (1.8%) without a bleeding precaution (P=0.03). All patients (5) who experienced a serious bleeding event died compared to 39 of 74 patients (52.7%) who did not (P=0.06). Seventeen of 24 patients (70.8%) with bleeding precautions died vs 27 of 55 patients (49.1%) without bleeding precautions (P=0.07). The number of serious bleeding events did not allow meaningful multivariate analyses. The mean number of failing organs was an independent predictor of 30-day post-discharge mortality (OR 1.63 for each organ failed, 95% CI 1.05-2.6). Conclusions: The findings of this study were consistent with our prior observations and suggest the risk for serious bleeding events with drotrecogin alfa (activated) may outweigh any potential benefit in patients with baseline bleeding precautions.