Antithrombin Deficiency Treatment & Management

Updated: Aug 22, 2019
  • Author: Bryan A Mitton, MD, PhD; Chief Editor: Perumal Thiagarajan, MD  more...
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Treatment

Approach Considerations

In patients with a known inherited antithrombin (AT) deficiency, management of an acute thrombotic event becomes challenging, as these patients may exhibit a variable response to even large doses of heparin. When a therapeutic response to intravenous heparin is not achievable, additional support with an antithrombin concentrate may be necessary. [56]  Currently, however, direct thrombin inhibitors (eg, argatroban, dabigatran) are recommended. These agents do not require antithrombin for their action. Anticoagulation can be achieved more easily and without the use of exogenous blood products.

For a planned major operation, correction of antithrombin levels using antithrombin concentrate products is recommended in patients with known antithrombin (AT) deficiency. In acute severe trauma, some studies also suggest a beneficial effect with antithrombin replacement.

In contrast to antithrombin concentrates, fresh frozen plasma (FFP) does not have a sufficient concentration of antithrombin to provide adequate replacement in patients who are significantly deficient, so FFP should not be used if alternatives are available. The goal of correction should be to antithrombin activity of 80% or greater, to achieve physiologic function.

Close consultation with a hematologist is necessary; obtain consultation with a geneticist as needed. The support of a laboratory equipped to assay antithrombin activity is necessary in patients receiving antithrombin replacement therapy.

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Prevention

Individuals with antithrombin deficiency who experience an unprovoked acute thromboembolic event are candidates for lifelong administration of an oral anticoagulant (vitamin K antagonists). Discontinuation of oral anticoagulants should be undertaken with great caution and only for essential procedures because of the risk of recurrent thromboembolic events. Replacement with antithrombin concentrate may be needed during such times.

Patients with known antithrombin deficiency may be considered candidates for antithrombotic prophylaxis during high-risk situations such as surgery and pregnancy.

Nishimura and Takagi reported five patients with ATIII deficiency who underwent cardiovascular surgery and were administered ATIII concentratenwithout postoperative complications such as hemorrhage or thrombosis. The authors concluded that in patients with ATIII deficiency undergoing cardiac surgery, it is important to perform ATIII replacement to achieve preoperative ATIII activity ≥120% and postoperative ATIII activity ≥80%, while the activated clotting time (ACT) is maintained at >400 seconds during cardiopulmonary bypass. [57]

In a study of  21 women with inherited AT deficiency who received recombinant human antithrombin (rhAT) therapy up to 24 hours before scheduled induction or cesarean delivery, or at the onset of labor, there were no reported cases of venous thromboembolism (VTE) within 7 days of dosing. However, two VTE events (one deep vein thrombosis and one pulmonary embolism) occurred 11 and 14 days after discontinuation of rhAT, in patients managed with prophylactic doses of heparin or low-molecular-weight heparin following delivery. [58]  

Rivaroxaban, a direct oral factor Xa inhibitor, has been shown to be non-inferior to existing treatments (such as warfarin or low-molecular-weight heparin) for preventing the recurrence of symptomatic DVT and PE. Successful perioperative use of rivaroxaban for prevention of thromboembolism in a patient with AT deficiency has been reported. [59, 60]

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