Table 1. Patients had to have a known or suspected infection, as evidenced by one or more of the following:

• white cells in a normally sterile body fluid;
• perforated viscus;
• radiographic evidence of pneumonia in association with the production of purulent sputum;
• a syndrome associated with a high risk of infection (e.g., ascending cholangitis).

• a core temperature of ≥ 38 °C (100.4 °F) or ≤ 36 °C (96.8 °F);
  
• a heart rate of ≥ 90 beats/min, except in patients with a medical condition known to increase the heart rate or those receiving treatment that would prevent tachycardia;
  
• a respiratory rate of ≥ 20 breaths/min or a PaCO2 of ≤ 32 mm Hg or the use of mechanical ventilation for an acute respiratory process;
  
• a white-cell count of ≥ 12,000/mm³ or ≤ 4,000/mm³ or a differential count showing > 10 percent immature neutrophils.

Table 3. Patients had to meet at least one of the following five organ dysfunction criteria:

• for cardiovascular system dysfunction, the arterial systolic blood pressure had to be ≤ 90 mm Hg or the mean arterial pressure ≤ 70 mm Hg for at least 1 hour despite adequate fluid resuscitation, adequate intravascular volume status or the use of vasopressors in an attempt to maintain a systolic blood pressure of ≥ 90 mm Hg or a mean arterial pressure of ≥ 70 mm Hg;
• for kidney dysfunction, urine output had to be < 0.5 ml/kg of body weight/hr for 1 hour, despite adequate fluid resuscitation;
  
• for respiratory-system dysfunction, the ratio of PaO2 to FiO2 had to be ≤ 250 in the presence of other dysfunctional organs or systems or ≤ 200 if the lung was the only dysfunctional organ;
  
• for hematologic dysfunction, the platelet count had to be < 80,000/mm³ or to have decreased by 50 percent in the 3 days preceding enrollment;
  
• in the case of unexplained metabolic acidosis, the pH had to be ≤ 7.30 or the base deficit had to be ≥ 5.0 mmol/liter in association with a plasma lactate level that was > 1.5 times the upper limit of the normal value for the reporting laboratory.

Exclusion criteria:
Pregnancy or breast-feeding.
Age <18 yr or weight >135 kg.
Platelet count <30,000/mm³.
Conditions that increased the risk of bleeding:

• surgery requiring general or spinal anesthesia within 12 hours before the infusion, the potential need for such surgery during the infusion, or evidence of active bleeding postoperatively;
  
• a history of severe head trauma requiring hospitalization, intracranial surgery, or stroke within 3 months before the study or any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system;
  
• a history of congenital bleeding diatheses;
  
• gastrointestinal bleeding within 6 weeks before the study unless corrective surgery had been performed;
  
• and trauma considered to increase the risk of bleeding.

• resistance to activated protein C;
• hereditary deficiency of protein C, protein S, or antithrombin III;
• presence of anticardiolipin antibody, antiphospholipid antibody, lupus anticoagulant, or homocysteinemia;
• or recently documented (within 3 months before the study)or highly suspected deep-vein thrombosis or pulmonary embolism.

• unfractionated heparin to treat an active thrombotic event within 8 hours before the infusion †;
  
• low-molecular-weight heparin at a higher dose than recommended for prophylactic use (as specified in the package insert) within 12 hours before the infusion;
  
• warfarin (if used within 7 days before study entry and if the prothrombin time exceeded the upper limit of the normal range for the institution);
  
• acetylsalicylic acid at a dose of more than 650 mg/day within 3 days before the study;
  
• thrombolytic therapy within 3 days before the study ‡;
  
• glycoprotein IIb/IIIa antagonists within 7 days before study entry;
  
• antithrombin III at a dose of more than 10,000 U within 12 hours before the study;
  
• or protein C within 24 hours before the study.

N.B. - The infusion was interrupted one (1) hour before any percutaneous procedure or major surgery and was resumed one (1) hour after the percutaneous procedure and 12 hours after major surgery, in the absence of bleeding complications.

In both the Xigris and placebo group, "serious bleeding occurred primarily in patients with an identifiable predisposition to bleeding, such as GI ulceration, activated partial-thromboplastin time > 120 secs, prolonged prothrombin time (an international normalized ratio of more than 3.0), a platelet count that decreased to less than 30,000 per mm³ and remained at that level despite standard therapy, traumatic injury of a blood vessel or traumatic injury of a highly vascular organ."

* Serious bleeding was defined as any intracranial hemorrhage, any life-threatening bleeding, any bleeding event classified as serious by the investigator or any bleeding that required the administration of 3 units of packed red cells on two consecutive days.