What is the management approach for a patient with suspected Antithrombin 3 (AT3) deficiency and normal Antigen values?

From the Guidelines

Management of a patient with suspected Antithrombin 3 (AT3) deficiency and normal Antigen values should prioritize confirming the diagnosis through functional AT3 activity testing. This approach is crucial as normal antigen values may indicate a type II deficiency where the protein is present but dysfunctional. Initial treatment includes anticoagulation with low molecular weight heparin (LMWH) such as enoxaparin 1mg/kg twice daily or unfractionated heparin with careful monitoring, as these patients may be heparin-resistant 1. For acute thrombotic events, AT3 concentrate (typically 50-100 IU/kg) should be administered to achieve AT3 activity levels above 80%. Long-term management involves indefinite oral anticoagulation with warfarin (target INR 2-3) or direct oral anticoagulants (DOACs) like rivaroxaban 20mg daily or apixaban 5mg twice daily. During high-risk periods such as surgery or pregnancy, prophylactic anticoagulation and potential AT3 supplementation are recommended, as suggested by guidelines for women with antithrombin deficiency and a family history of VTE 1. Key considerations include:

• Genetic testing for confirmation and family screening, given the autosomal dominant inheritance pattern of AT3 deficiency
• Regular monitoring of AT3 activity levels to guide treatment adjustments, particularly during acute thrombotic episodes or high-risk situations
• Adherence to anticoagulation therapy to minimize the risk of venous thromboembolic events, considering the patient's specific risk factors and clinical context.

From the Research

Antithrombin 3 Deficiency Management

• The management approach for a patient with suspected Antithrombin 3 (AT3) deficiency and normal Antigen values involves a thorough assessment of venous thromboembolism (VTE) risk, comprising the degree and type of AT deficiency, genetic mutations, personal and family history, and additional preexisting or pregnancy-specific risk factors 2.
• Low-molecular-weight heparin (LMWH) is the medication of choice for the pharmacological prophylaxis and treatment of VTE in pregnancy, and patients with a history of VTE should receive full-dose LMWH during pregnancy and the postpartum period 2.
• Antithrombin concentrates are a treatment option when anticoagulation is withheld in potentially high-risk events such as childbirth, bleeding, or surgery and in cases of acute VTE despite the use of therapeutic dose anticoagulation 2.
• Direct oral anticoagulants (DOACs) may also be considered, as they appear to be efficacious and relatively safe in patients with inherited antithrombin deficiency, with a low VTE recurrence rate and minimal bleeding risk 3.

Normal Antigen Values

• Normal values for antithrombin III (AT III) antigen in plasma were obtained by testing samples from 20 normal subjects, and patients who had decreased AT III activity in the functional assays also had decreased AT III antigen 4.
• However, the presence of normal antigen values does not necessarily rule out AT3 deficiency, as the condition can be caused by a variety of genetic mutations and other factors 2.

Pregnancy Considerations

• Pregnancy is a high-risk period for VTE in women with AT3 deficiency, and close cooperation between obstetricians and anesthesiologists is warranted before delivery and during the peripartum period 2, 5.
• Women with AT deficiency should be counseled at specialized centers for coagulation disorders or vascular medicine, and prophylactic anticoagulation should be considered throughout pregnancy, especially in patients with a history of thrombosis 2, 5.