• Kevin E Anger, Jeremy R Degrado, Bonnie C Greenwood, Steven A Cohen, and Paul M Szumita.
• Department of Pharmacy, Brigham and Women's Hospital, Boston, MA, USA.
• Ther Clin Risk Manag. 2013 Jan 1; 9: 277-84.

PurposeEarly clinical trials of recombinant human activated protein C (rhAPC) for severe sepsis excluded patients at high risk of bleeding. Recent literature suggests bleeding rates are higher in clinical practice and may be associated with worsened outcomes. Our objective was to evaluate baseline demographics; incidence, and risk factors for major bleeding; and mortality of patients receiving rhAPC for severe sepsis at our institution.MethodsA retrospective study was performed for all patients receiving rhAPC for treatment of severe sepsis at a tertiary academic medical center from January 2002 to June 2009. Demographic information, clinical variables, intensive care unit, and hospital outcomes were recorded.ResultsOf the 156 patients that received rhAPC, 54 (34.6%) did not meet institutional criteria for safe use at baseline due to bleeding precaution or contraindication. Twenty-three (14.7%) patients experienced a major bleeding event. Multivariate analysis demonstrated baseline International Normalized Ratio ≥2.5 (odds ratio [OR] 3.68, 95% confidence interval [CI]: 1.28-10.56; P = 0.03) and platelet count ≤100 × 10(3)/mm(3) (OR 2.86, 95% CI: 1.07-7.67; P = 0.01) as significant predictors of a major bleed. Overall hospital mortality was 57.7%. Multivariate analysis demonstrated the presence of ≥3 organ dysfunctions (OR 2.46, 95% CI: 1.19-5.09; P < 0.05) and medical intensive care unit admission (OR 1.99, 95% CI: 1.00-3.98; P = 0.05) were independent variables associated with hospital mortality.ConclusionPatients receiving rhAPC at our institution had higher APACHE II scores, mortality, and major bleeding events than published postmarketing studies. Risk factors for major bleeding other than package-labeling contraindications and bleeding precautions were identified in our patient population.

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