Challenge and Rechallenge: Drotrecogin alfa (activated)–Induced Prolongation of Activated Partial Thromboplastin Time in a Patient with Severe Sepsis

An 81-year-old woman with ischemic bowel underwent laparotomy with small-bowel resection and developed septic shock. She required broadspectrum antibiotics, norepinephrine, and mechanical ventilation. The patient received drotrecogin alfa (activated) 24 μg/kg/hour for a total of 67.5 hours. Coagulation parameters were monitored during her therapy. Significant increases in activated partial thromboplastin time (aPTT) during infusion led to two temporary discontinuations of the drug. Coagulation parameters decreased when the drug was held and increased with each rechallenge. The patient survived the episode and was discharged on postoperative day 27. Medical records of 26 other patients who received drotrecogin alfa (activated) at our institution from November 2001–August 2003 were reviewed retrospectively for coagulation parameters and bleeding rate. Of the 26 patients, nine (35%) were treatment compliant (> 90% of the 96-hr course). Coagulopathy and bleeding resulted in early discontinuation in four (15%) and six (23%) patients, respectively. An increase in aPTT from baseline to during infusion of drotrecogin alfa (activated) was noted in 14 patients with complete data (p=0.56). A decrease in median platelet count from baseline to during infusion was noted in the six patients who bled during therapy (p=0.01). Two of these patients had platelet counts less than 30 × 10³/mm³ during administration. Drotrecogin alfa (activated) should be considered an anticoagulant. In postmarketing reports, clinically significant bleeding occurred more frequently than was noted in a large, randomized, multicenter trial. Patients receiving drotrecogin alfa (activated) should be closely monitored for prolongation of coagulation parameters. Temporary discontinuation of the drug should be considered when international normalized ratio is greater than 3.0, platelet count is less than 15 × 10³/mm³, and aPTT is greater than 100 seconds.