Critical Care Medicine
In addition to anti-inflammatory properties, activated protein C also possesses anticoagulant and profibrinolytic properties, and, not unexpectedly, these properties increase the risk of bleeding in patients receiving drotrecogin alfa (activated). In the PROWESS trial, bleeding was the only adverse effect of administration of drotrecogin alfa (activated).1 Serious bleeding, defined as intracranial hemorrhage, life-threatening bleed, or bleeding that required administration of 3 U of packed RBCs on 2 consecutive days, occurred in 3.5% of patients receiving drotrecogin alfa (activated) as compared with 2% of those receiving placebo. This increased risk occurred primarily during the peri-infusion period. Any bleeding event during the 28-day study period also occurred more frequently in patients receiving drotrecogin alfa (activated) (24.9% versus 17.7% with placebo). rhAPC should not be given to any patient with a recent history (within 3 months) of hemorrhagic stroke due to the risk of intracranial hemorrhage. Post hoc analysis of PROWESS trial data found that increased bleeding was associated with a platelet count that fell below 30,000 cells/µL and/or INR that rose above 3.0.1 As such, both represent relative contraindications to administration of rhAPC; the case patient has adequate platelets and an acceptable INR for rhAPC. Uncomplicated bedside procedures (eg, lumbar puncture) are not contraindications to rhAPC therapy; rhAPC should be discontinued for 2 hours prior to the procedure and restarted once hemostasis is acheived.
- Previous hemorrhagic CVA.
1. Bernard GR, Vincent JL, Laterre PF, et al; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699–709.
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