Inclusion Criteria

To be considered for rhAPC therapy the patient should have:

1. A known or suspected site of infection as indicated by one or more of the following:

1. Purulent sputum or respiratory sample or a CXR with new infiltrates not explained by a non-infectious process
2. Spillage of bowel contents noted during an operation
3. Radiographic or physical exam evidence of an infected collection
4. White blood cells in a normally sterile body fluid
5. Positive Blood culture
6. Evidence of infected mechanical hardware by physical or radiological exam

1. Evidence of systemic inflammation syndrome as indicated by at least 3 of the following:

1. Fever or hypothermia: core temp > 38° C or < 36° C
2. Respiratory Dysfunction as defined as
   1)Tachypnea: > 20 breaths/minute or
   2) Mechanical ventilation for an acute process or
   3)PaCO2<32mm Hg
3. Heart rate:> to 90 beats/minute.
   Patient only needs to meet 2 of the other criteria if:
   1) the patient has a pacemaker, or
   2) the patient is on pharmacological therapy for a pre-existing tachycardia
4. White Blood Cell Count: > 12,000 cells/mm³ or < 4000 cells/mm³ or 10% bands on WBC differential

1. Sepsis-Induced Organ Failure Criteria:

1. The need for vasopressors to maintain adequate blood pressure after an adequate volume replacement or fluid challenge

1. Respiratory: PaO₂/FIO₂ ratio < 200
2. Renal: Urine output < 0.5 ml/kg/hr for 2 hour in the face of adequate intravascular volume (CVP > 8 or PAWP > 12), or after an adequate fluid challenge (12 cc/kg) has been given
3. Hematologic: Thrombocytopenia (as defined as < 80,000 platelets/ mm³ but >30,000 platelets/ mm³) or a 50% drop in the last 3 days
4. Unexplained metabolic acidosis: pH < 7.30 with an elevated plasma lactate level that is > 1.5 times the upper limit of normal

Exclusion Criteria

1. Patients with surgery in the previous 12 hours
2. Thrombocytopenia < 30,000 platelets/mm³
3. Patient requiring therapeutic doses of heparin (> 15000 Units/day) to treat a thrombotic condition within the previous 8 hours, LMWH at a dose higher than prophylaxis within in the previous 12 hours
4. Patients who have received systemic thrombolytic therapy within the past 3 days, ASA > 650 mg/day within the past 3 days, Glycoprotein IIb/IIIa antagonists within the past 7 days, warfarin within the past 4 days, or clopidogrel or ticlopidine within the past 4 days
5. INR >3 or aPTT>100 seconds
6. Evidence of post-operative bleeding
7. Evidence of active and clinically significant gastrointestinal bleeding
8. Patients with a central nervous system mass lesion, stroke within 3 months, history of AVM, cerebral aneurysm, intracranial surgery, or history of severe head trauma requiring hospitalization
9. Patients with cirrhosis (history of esophageal varicies, portal hypertension, or Child's Class C)
10. Patients with a new nephrostomy tube or evidence of a bleeding complication following a percutaneous procedure, e.g.:
    a)Decreasing Hgb
    b)Flank hematoma after femoral line placement
11. Patients with unexplained mental status changes or neurologic exam changes in whom a CT scan has not been performed to rule out a mass lesion or CNS bleed
12. Patients with end-stage disease processes in which there is not a commitment to aggressive management of the patient
13. Patients enrolled in a clinical trial involving a molecule that targets the coagulation cascade
14. Patients with pulmonary, splenic or liver contusions following trauma
15. Patients with an epidural catheter in place within 12 hours of initiation of therapy w rhAPC
16. Pediatric patients only with approval of Pediatric Infectious Disease or unless treating purpura fulminans

Guidelines for Monitoring rhAPC Use

1. rhAPC should be dosed based on patient ideal body weight
   a)for males:50Kg + 2.3Kg for every inch in height over 5 feet
   b)for females:45Kg + 2.3Kg for every inch of height over 5 feet
   c)for patients weighing less than ideal body weight, actual weight should be used
2. Patients should be given 24 mcg/kg/hr of rhAPC as a continuous infusion for 96 hours.
3. If a surgery or percutaneous procedure or epidural catheter needs to be performed, rhAPC should be stopped 2 hours prior to the procedure.


rhAPC can be restarted 1 hour after a percutaneous procedure and 12 hours after a surgical procedure, lumbar puncture or epidural catheter removal if adequate hemostasis has been achieved.

4. If evidence of GI bleeding occurs, rhAPC should be stopped and the cause of the bleeding investigated
5. Patients receiving rhAPC should be on some form of gastroprotective agent such as sucralfate, a histamine-2 antagonist, or a proton-pump inhibitor.
6. If a patient requires full-dose therapeutic heparin for the treatment of a thrombotic event, the rhAPC infusion should be stopped.
7. If a patient requires renal replacement therapy, attempts should be made to run the dialysis with rhAPC alone, if clotting occurs, the lowest dose of heparin necessary to maintain the patency of the dialysis filter should be used.

Approval Process

1. rhAPC is NOT a STAT agent.
2. Orders for rhAPC received in the pharmacy between 10 pm and 7 am will be dealt with after 7 am (except in the case of meningococcal infections).
3. The pharmacist will review the review the case for eligibility. In all cases, Infectious Disease consultation is required to ensure appropriate antibiotic coverage during rhAPC use. In the event the patient is deemed ineligible, and the attending physician of record wishes to proceed, the case will be brought to one of the prenamed intensivist sponsors for adjudication
4. Routine review of the appropriate use of this agent will be performed

*These guidelines were developed based on those drafted by Dr. S. Larosa and colleagues at the Cleveland Clinic Foundation