Antithrombin III Deficiency Medication

Updated: Feb 10, 2018
  • Author: James L Harper, MD; Chief Editor: Hassan M Yaish, MD  more...
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Medication

Medication Summary

Antithrombin III (ATIII) deficiency may be quickly corrected with infusions of antithrombin III concentrates. Long-term therapy for congenital deficiency is generally not indicated, as an asymptomatic period may last decades. Once thrombosis has occurred, warfarin therapy is generally undertaken.

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Antithrombin-III concentrates

Class Summary

Antithrombin III concentrate (Thrombate III [Bayer Corporation]) is used for replacement therapy. This product is a plasma-derived concentrate made from pooled human plasma using modified Cohn ethanol separation and heat-treated for viral inactivation. The vials have no preservatives and are labeled in international units calibrated against a World Health Organization (WHO) standard.

Antithrombin, recombinant (ATryn)

Recombinant AT made in goats. AT regulates hemostasis by inhibiting thrombin and factor Xa, key proteases for blood coagulation. Indicated for prevention of perioperative and peripartum thromboembolic events in patients with hereditary AT deficiency. Not indicated for treatment of thromboembolic events. Available as a lyophilized powder that is reconstitution for IV infusion. Normally administered as a continuous IV infusion medication.

Antithrombin III (Thrombate III)

Alpha2-globulin that inactivates thrombin; plasmin; and other serine proteases of coagulation including factors IXa, Xa, XIa, XIIa, and VIIa, which, in turn, inhibits coagulation.

Mean recovery in healthy patients is 1.6% activity/U/kg infused (ie, 160% activity when 100 U/kg is infused) based on immunologic ATIII assays. Recovery based on functional assays is 1.4% activity/U/kg (ie, 140% activity when 100 U/kg is infused). Functional assay results are most commonly used to calculate dose. Half-life of ATIII is approximately 22 h. This number should be considered in light of patient's underlying clinical problems, as the rate of ATIII consumption may be increased, which would affect extent of recovery and half-life.

A target of 120% is the upper limit of the reference range for ATIII and is chosen as a target value to allow for maximum amount of time to elapse before clearance and consumption of ATIII drops the level in patient's plasma to < 80%.

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Anticoagulants

Class Summary

In patients with congenital ATIII deficiency, anticoagulation reduces the incidence of thrombosis. The duration of therapy is likely to be indefinite.

Warfarin (Coumadin)

Inhibits vitamin K–dependent gamma carboxylation of procoagulant proteins factor II, VII, IX, X, as well as the anticoagulant factor, protein C. Tailor dose to maintain an INR in the range of 2-2.5. The length of time to achieve target INR is age dependent. In infants, the median time to achieve the target INR is 5 d and in adolescents, 3 d.

Enoxaparin (Lovenox)

Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). Binds to ATIII, enhancing its therapeutic effect. The heparin-ATIII complex binds to and inactivates activated factor X (Xa) and factor II (thrombin).

Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Advantages include intermittent dosing and decreased requirement for monitoring. Heparin antifactor Xa levels may be obtained if needed to establish adequate dosing.

LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared with UFH.

Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Used for prevention in hip replacement surgery (during and following hospitalization), knee replacement surgery, or abdominal surgery in those at risk of thromboembolic complications, or in nonsurgical patients at risk of thromboembolic complications secondary to severely restricted mobility during acute illness.

Used for the treatment of DVT or PE in conjunction with warfarin, for the inpatient treatment of acute DVT with or without PE, or for the outpatient treatment of acute DVT without PE.

No use in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect). Average duration of treatment is 7-14 d.

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