Management of Antithrombin III Deficiency

Understanding AT III Deficiency

The American Heart Association notes that AT III 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 1
Congenital AT III deficiency typically presents with AT III levels <50% of normal, with patients often experiencing lower-extremity venous thrombosis and pulmonary embolism in teenage years or young adulthood 1
Normal newborns and infants have physiologically lower AT III levels (20-80% of adult values) that approach adult values by 6 months of age 1

AT III deficiency increases risk of thrombosis, particularly venous thromboembolism 2
Patients with AT III deficiency are at higher risk during specific situations, including surgery and perioperative periods 3, and prolonged immobilization or concurrent use of oral contraceptives or hormone therapy 4

The American College of Cardiology recommends long-term anticoagulation with vitamin K antagonists (target INR 2.0-3.0) for patients with history of thrombosis 5
For acute thrombotic events, initial treatment with heparin followed by transition to oral anticoagulants is recommended 4

Patients with AT III deficiency may exhibit heparin resistance, defined as inability to achieve ACT >300 seconds despite administration of >600 U/kg heparin 1
Heparin resistance should be suspected when the ACT fails to prolong beyond 300 seconds despite high-dose heparin administration 1

AT III supplementation is indicated for patients with inherited AT III deficiency when heparin resistance is present 1

Regular monitoring of coagulation parameters is essential, including Activated Partial Thromboplastin Time (APTT) - target 1.5-2.5 times control value 6, and Anti-Factor Xa levels - target 0.3-0.7 U/mL for patients on extracorporeal support 6
AT III concentrate availability may be limited; fresh frozen plasma can be used as an alternative source of AT III but has disadvantages including volume load and transfusion-related complications 1

The British Journal of Anaesthesia recommends antithrombin concentrate as the primary treatment of antithrombin deficiency to improve heparin sensitivity 7
If antithrombin concentrate is unavailable, the British Journal of Anaesthesia suggests fresh frozen plasma as an alternative to treat antithrombin deficiency and improve heparin sensitivity 7

The American College of Obstetricians and Gynecologists, as reported in Blood advances, recommends postpartum antithrombotic prophylaxis for women with a family history of VTE who have antithrombin deficiency to prevent a first venous thromboembolic event 8

The Society of Critical Care Medicine, as reported in Critical Care, advises against the use of antithrombin concentrates in the treatment of bleeding trauma patients 9, 10, 11

Testing for antithrombin deficiency is recommended in patients with venous thromboembolism occurring at a young age, in the absence of identifiable risk factors, especially when there is a strong family history of VTE, as recommended by the European Society of Cardiology 12
Testing is recommended for patients with a first episode of VTE occurring in the absence of a major reversible risk factor, as AT deficiency is a major persistent pro-thrombotic condition that may warrant indefinite anticoagulation, according to the European Heart Journal 13, 12
Testing should be considered in patients with recurrent VTE episodes, as AT deficiency significantly increases the risk of recurrence, as stated by the European Heart Journal 12
Testing is appropriate for first-degree relatives of individuals with confirmed AT deficiency, particularly if the index case had thrombotic events, as recommended by the American College of Medical Genetics 14
Testing should be considered in patients with VTE at unusual body sites, as suggested by the American College of Medical Genetics 14
Testing may be appropriate for patients with thrombosis during pregnancy, as recommended by the American College of Medical Genetics 14

Before diagnosing hereditary AT deficiency, rule out acquired causes of low AT levels, such as liver dysfunction, as recommended by the American Thoracic Society 15
Before diagnosing hereditary AT deficiency, rule out acquired causes of low AT levels, such as proteinuria/nephrotic syndrome, as recommended by the American Thoracic Society 15
Before diagnosing hereditary AT deficiency, rule out acquired causes of low AT levels, such as disseminated intravascular coagulation (DIC), as recommended by the American Society of Hematology 16
Before diagnosing hereditary AT deficiency, rule out acquired causes of low AT levels, such as acute thrombosis, as recommended by the European Society of Cardiology 13
Before diagnosing hereditary AT deficiency, rule out acquired causes of low AT levels, such as recent surgery, as recommended by the American Society of Hematology 17
Before diagnosing hereditary AT deficiency, rule out acquired causes of low AT levels, such as oral contraceptive use, as recommended by the American College of Medical Genetics 14

Confirmed AT deficiency has significant implications for anticoagulation management and duration, as stated by the European Society of Cardiology 12
Patients with AT deficiency and a history of VTE are often candidates for indefinite anticoagulant treatment, as recommended by the European Society of Cardiology 13, 12
In pediatric patients with VTE who have failed to respond clinically to standard anticoagulation, AT level measurement may be indicated to guide potential AT replacement therapy, as recommended by the American Society of Hematology 17, 16