Treatment of Antithrombin Deficiency

Antithrombin concentrate is recommended as the primary treatment of antithrombin deficiency to improve heparin sensitivity. 1

Understanding Antithrombin Deficiency

Antithrombin (AT) is a glycoprotein that functions as a potent natural anticoagulant and serine protease inhibitor, inactivating many enzymes in the coagulation cascade, particularly factors IIa (thrombin) and Xa 2
AT deficiency can be inherited (autosomal dominant with prevalence of 1 in 2000 to 1 in 20,000) or acquired, and is associated with increased risk of venous thromboembolism 3
Congenital AT deficiency is one of the most severe inherited thrombophilias, with up to 85% lifetime risk of venous thromboembolism 4
Acquired AT deficiency can arise during heparin therapy or states of hypercoagulability like sepsis and premature infancy 4

Antithrombin concentrate is recommended as the primary treatment of antithrombin deficiency to improve heparin sensitivity 1
If antithrombin concentrate is unavailable, fresh frozen plasma (FFP) should be considered to treat antithrombin deficiency to improve heparin sensitivity 1

For patients with a history of thrombosis, long-term anticoagulation with vitamin K antagonists (target INR 2.0-3.0) is recommended 3
For acute thrombotic events, initial treatment with heparin followed by transition to oral anticoagulants is recommended 3
Standard-dose direct oral anticoagulants (DOACs) appear efficacious and relatively safe in inherited antithrombin deficiency, with a VTE recurrence rate of 0.5/100 patient-years in compliant users 5

Patients with AT deficiency may exhibit heparin resistance, defined as inability to achieve adequate anticoagulation despite high doses of heparin 3
The anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency 6
To reduce the risk of bleeding, a reduced dosage of heparin is recommended during treatment with antithrombin III (human) 6

Short-term thromboprophylaxis is recommended in high-risk clinical settings, including surgery and trauma 7
The goal of treatment for patients with hereditary AT deficiency is an initial increase in AT activity to ≥120% of normal levels followed by maintenance of AT activity at ≥80% of normal levels 7

Optimization of AT levels is an important treatment consideration during pregnancy and postpartum 4
Antithrombin concentrate is often used around the time of birth when low molecular weight heparin (LMWH) may increase the risk of post-partum hemorrhage 2
For women with a family history of VTE who have antithrombin deficiency, postpartum antithrombotic prophylaxis is recommended to prevent a first venous thromboembolic event 1

Regular monitoring of coagulation parameters is essential, including Activated Partial Thromboplastin Time (APTT) - target 1.5-2.5 times control value 3
Anti-Factor Xa levels should be monitored in patients on extracorporeal support - target 0.3-0.7 U/mL 3
Patients on long-term anticoagulation should be assessed periodically for bleeding risk 2

AT concentrate availability may be limited; fresh frozen plasma can be used as an alternative source of AT but has disadvantages including volume load and transfusion-related complications 3
Prophylactic anticoagulation is not recommended in asymptomatic patients with AT deficiency because of the increased risk of hemorrhage 7
Antithrombin concentrates are not recommended in the treatment of bleeding trauma patients 1
The concurrent use of any form of heparin with antithrombin treatment in sepsis settings may remove whatever benefit may be derived from antithrombin treatment 2