Therapeutic rationale for antithrombin III in sepsis

Objective: To review the preclinical evidence that provides the therapeutic rationale for antithrombin as a novel treatment for human sepsis. Data Sources: A summary of published medical literature from MEDLINE search files and other reviews published about antithrombin use in sepsis. Data Summary: Antithrombin has a variety of anti-inflammatory properties in addition to its functions as an endogenous anticoagulant that appear to have an important therapeutic role in the prevention of microvascular dysfunction and multiple organ injury in sepsis. Appropriate timing and dosing of antithrombin III is critical to realize its full therapeutic potential as an anti-sepsis therapy. Conclusions: Antithrombin is a potent inhibitor of thrombin-mediated vascular injury in the microcirculation in severe sepsis. This endogenous anticoagulant is rapidly depleted in the early phases of sepsis as a result of decreased synthesis, increased destruction, and enhanced clearance by thrombin-antithrombin complex formation. The therapeutic efficacy of antithrombin in experimental sepsis is readily demonstrable in numerous animal systems. Appropriately defined patient populations with early onset severe sepsis and/or septic shock may benefit from antithrombin therapy if it is administered in adequate doses at the optimal time interval.