High-dose antithrombin III therapy had no effect on 28-day all-cause mortality in adult patients with severe sepsis and septic shock when administered within 6 hours after the onset. High-dose antithrombin III was associated with an increased risk of hemorrhage when administered with heparin. There was some evidence to suggest a treatment benefit of antithrombin III in the subgroup of patients not receiving concomitant heparin.

). At 30 min thereafter, INR declined to £1.3 in 93% of patients. At all postinfusion time points through 48 h, median INR remained between 1.2 and 1.3. Clinical hemostatic efficacy was classified as very good or satisfactory in 42 patients (98%). Prompt and sustained increases in circulating coagulation factors and anticoagulant proteins were observed. One fatal suspected pulmonary embolism in a patient with metastatic cancer was judged to be possibly PCCrelated. Conclusions: PCC treatment serves as an effective rapid hemorrhage control resource in the emergency anticoagulant reversal setting. More widespread availability of PCC is warranted to ensure its benefits in appropriate patients.

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Summary. Background: Although fibrinogen concentrate has been available for the treatment of congenital fibrinogen deficiency for years, knowledge of its pharmacokinetics comes from only two small studies. Objectives: To assess the pharmacokinetic (PK) profile, clot integrity and safety of fibrinogen concentrate (human) (FCH) in patients with afibrinogenemia. Patients and methods: A multinational, prospective, open-label, uncontrolled study of patients with afibrinogenemia ‡ 6 years of age was conducted in the USA and Italy. Plasma was collected before and after infusion for PK analyses and evaluation by rotational thromboelastometry of maximum clot firmness (MCF) to assess clot integrity. Safety was assessed on the basis of adverse events and laboratory parameters. Results: After a single dose of 70 mg kg )1 body weight (b.w.)FCH in 14 patients, median incremental in vivo recovery was a 1.7 mg dL )1 increase per mg kg )1 b.w., and median levels were 1.3 g L )1 for fibrinogen activity and antigen 1 h after infusion.Median half-life (t 1/2 ) was 77.1 h for fibrinogen activity and 88.0 h for antigen. Plasma recovery in children < 16 years old was similar to that in adults aged 16 to < 65 years, but the t 1/2 and area under the curve were decreased, with an increased steady-state volume and clearance. MCF increased by a mean of 8.9 mm from baseline to 1 h after infusion of FCH (P < 0.0001). All four adverse events reported were mild, and none was serious or related to study drug. Conclusions: These PK findings confirm a rapid increase in plasma fibrinogen levels after infusion with FCH. Together with the clot integrity and safety data and published data on efficacy, the results support the idea that FCH substitution can restore hemostasis with a good safety profile.