From the Guidelines
Antithrombin III deficiency is a condition that requires careful management with anticoagulation as the primary treatment, with antithrombin replacement therapy considered only in specific scenarios where there is progressive clinical thrombosis that is failing to respond to anticoagulation alone, as suggested by the American Society of Hematology 2018 guidelines 1. The pathophysiology of antithrombin III deficiency involves impaired inhibition of activated clotting factors, particularly thrombin and factor Xa, resulting in excessive clot formation and a hypercoagulable state. For medical workup, the following tests are recommended:
- Antithrombin activity levels (functional assay)
- Antithrombin antigen levels (immunologic assay)
- Complete thrombophilia panel
- Coagulation studies (PT, PTT)
- D-dimer
- Imaging studies if thrombosis is suspected Treatment focuses on preventing thrombotic events through anticoagulation, with the first line of treatment being anticoagulation, independent of the AT level, as stated in the guidelines 1. The treatment approach includes:
- Initial therapy with heparin (unfractionated or low molecular weight) for acute thrombosis
- Long-term warfarin with a target INR of 2.0-3.0
- Direct oral anticoagulants may be considered in some cases
- Prophylactic anticoagulation for high-risk situations like surgery or pregnancy
- Antithrombin concentrates may be necessary during acute thrombotic events, surgery, or childbirth to temporarily restore antithrombin levels, but the evidence for this is of very low certainty and the risk of bleeding must be carefully considered 1. Lifelong management with regular monitoring of anticoagulation therapy and education about thrombosis symptoms is crucial, as this genetic disorder significantly increases lifetime thrombotic risk, particularly during high-risk periods such as immobilization, surgery, or pregnancy.
From the Research
Pathophysiology of Antithrombin 3 Deficiency
- Antithrombin 3 deficiency is a condition characterized by a lack of antithrombin, a protein that helps regulate blood clotting [(2,3,4)].
- Antithrombin inhibits multiple procoagulant serine proteases, acting as an endogenous anticoagulant 4.
- Congenital antithrombin deficiency constitutes a major thrombophilic state, increasing the risk of venous thrombosis 4.
Medical Workup
- Diagnosis of antithrombin 3 deficiency involves measuring antithrombin activity levels [(3,4)].
- Patients with suspected heparin resistance should have their antithrombin activity levels checked, as antithrombin deficiency is a common cause of heparin resistance 3.
- Medical workup may also involve assessing the patient's thrombosis risk, particularly in high-risk situations such as surgery and pregnancy 4.
Treatment
- Treatment of antithrombin 3 deficiency typically involves anticoagulation therapy, such as warfarin or heparin [(2,3,5)].
- Antithrombin concentrates may be used to treat acute venous thrombosis in patients with antithrombin deficiency 4.
- In cases of heparin resistance, antithrombin substitution may be necessary to achieve adequate anticoagulation [(3,5)].
- Argatroban, a direct thrombin inhibitor, may be used as an alternative to heparin in patients with heparin-induced thrombocytopenia 6.
- The goal of treatment is to prevent thrombosis and manage anticoagulation, particularly in high-risk situations [(2,4)].