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To the Editor: Dr Warren and colleagues¹ reported that antithrombin III (AT) did not improve clinical outcomes in patients with severe sepsis or septic shock. These results are surprising in light of evidence of a procoagulant state during severe sepsis, which can be favorably affected by activated protein C (APC).² Without a full understanding of the mechanisms of APC and AT activity, we are left with the empirical finding that a 4-day treatment of APC is helpful while 4 days of AT is not.

Warren et al also raise the issue of the concomitant treatment with low-dose heparin, which was allowed in the protocol at a dosage commonly used to prevent deep venous thrombosis or catheter occlusion. When comparing 28-day mortality in the group of patients treated with AT but not with heparin (37.8%) and the patients who received neither AT nor heparin (43.6%), the difference in survival rates approaches . . . [Full Text of this Article]

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