Antithrombin III deficiency: clinical relevance and replacement therapy

Area of Science:

• Hematology
• Thrombosis Research

Background:

• Inherited antithrombin III (ATIII) deficiency is a known risk factor for venous thromboembolism (VTE).
• The clinical significance of acquired ATIII deficiency, including that associated with oral contraceptives, is not well-established.
• The efficacy of antithrombin III replacement therapy is largely unproven.

Purpose of the Study:

• To evaluate the clinical importance of acquired antithrombin III deficiency.
• To assess the utility of ATIII activity monitoring in surgical and heparin-treated patients.
• To review the evidence for antithrombin III replacement therapy.

Main Methods:

• Literature review and analysis of existing clinical data.
• Assessment of ATIII activity as a predictor of VTE risk.
• Evaluation of ATIII replacement therapy in congenital deficiency and disseminated intravascular coagulation (DIC).

Main Results:

• Moderately reduced ATIII activity lacks sensitivity and specificity for predicting postoperative VTE.
• Reduced ATIII activity during heparin therapy does not predict heparin requirements or recurrence.
• Evidence supporting ATIII replacement therapy in congenital deficiency is anecdotal; benefits in DIC require further demonstration.

Conclusions:

• The clinical role of acquired ATIII deficiency remains uncertain.
• Current measures of ATIII activity are poor predictors of VTE risk in surgical or heparinized patients.
• The benefits of ATIII replacement therapy on morbidity and mortality are not yet demonstrated.