Antithrombin III Measurement and Treatment

Introduction to AT III Deficiency

The American College of Cardiology recommends that Antithrombin III (AT III) deficiency should be treated with AT III concentrate as the primary intervention, especially in cases of heparin resistance, as it provides superior clinical outcomes compared to alternatives like fresh frozen plasma 1

AT III activity is primarily measured through functional assays that assess its enzymatic inhibitory action against serine proteases (thrombin and factor Xa) 2
Anti-Xa activity assays can indirectly reflect AT III function 2

AT III deficiency can be inherited (autosomal dominant with prevalence of 1 in 2000 to 1 in 20,000) or acquired 3
Congenital AT III deficiency typically presents with AT III levels <50% of normal, with increased risk of venous thromboembolism 3
Normal newborns and infants have physiologically lower AT III levels (20-80% of adult values) that approach adult values by 6 months of age 3

Heparin resistance should be suspected when the Activated Clotting Time (ACT) fails to prolong beyond 300 seconds despite administration of >600 U/kg heparin 3
AT III deficiency is a major cause of heparin resistance as heparin's anticoagulant effect depends on AT III 2
In patients with suspected heparin resistance, AT III levels should be measured before initiating treatment 3

AT III concentrate is the preferred treatment for AT III deficiency, particularly in cases of heparin resistance 1
AT III concentrate is a stable, lyophilized product derived from pooled normal human plasma, purified, and heat-treated to eliminate viral transmission 3
Advantages of AT III concentrate over fresh frozen plasma include diminished volume load, absence of transfusion-related complications, rapid availability, and more predictable increase in AT III levels 3, 1

Regular monitoring of coagulation parameters is essential during treatment, including Activated Partial Thromboplastin Time (aPTT) with a target of 1.5-2.5 times control value 1
Anti-Factor Xa levels should be targeted at 0.3-0.7 U/mL for patients on extracorporeal support 1
ACT should be checked at least every 30 minutes during cardiopulmonary bypass 3

For patients undergoing cardiopulmonary bypass with AT III deficiency, target ACT should be achieved before initiating cardiopulmonary bypass, and additional heparin should be given if ACT is below target value 3
Postpartum antithrombotic prophylaxis is recommended for women with AT III deficiency and family history of venous thromboembolism 1

Anti-Xa assays used to monitor heparin therapy can be affected by concurrent use of direct oral anticoagulants (DOACs), potentially leading to falsely elevated results 4
Before diagnosing hereditary AT III deficiency, rule out acquired causes of low AT III levels such as liver dysfunction, proteinuria, DIC, acute thrombosis, recent surgery, or oral contraceptive use 1