What is the management for patients with low antithrombin III (AT III) levels?

Management of Low Antithrombin III Levels

Patients with low antithrombin III (AT III) levels should receive AT III concentrate replacement therapy during high-risk periods and appropriate anticoagulation based on their thrombotic risk profile. 1

Evaluation of Low AT III Levels

• Determine if deficiency is hereditary (congenital) or acquired:

  • Hereditary: Autosomal dominant transmission, typically presents with thrombosis around age 20-30 2
  • Acquired: More common, associated with liver disease, nephrotic syndrome, DIC, or ECMO therapy 1, 2

• Assess current thrombotic risk:

  • History of previous thromboembolism
  • Presence of additional thrombophilias
  • Current clinical situation (surgery, pregnancy, immobilization)

Management Algorithm

1. For Acute Thrombosis with AT III Deficiency:

• Immediate intervention:

  • Administer AT III concentrate to achieve AT III activity of at least 80% of normal value 1, 3
  • Calculate dose based on current AT III level (target >80-100%)
  • Monitor AT III levels daily during acute treatment

• Anticoagulation:

  • Start heparin therapy (IV or LMWH) 2
  • Be aware that heparin resistance may occur due to AT III deficiency 4
  • Higher than usual heparin dosing may be required due to AT III urinary loss 1
  • Monitor anti-FXa levels and PTT more frequently than standard protocols 1

2. For Prophylaxis in High-Risk Situations:

• Perioperative management:

  • Administer AT III concentrate 1 hour before surgery 3
  • Target AT III activity level of at least 120% 3
  • Continue monitoring AT III levels (half-life approximately 7-14 hours) 3
  • Add prophylactic anticoagulation with LMWH or unfractionated heparin 3

• Pregnancy:

  • AT III concentrate throughout pregnancy for women with AT III deficiency 2
  • Avoid oral contraceptives in women with AT III deficiency 2

3. For Long-Term Management:

• Chronic anticoagulation:

  • Warfarin (target INR 2.0-3.0) is the anticoagulant of choice for long-term therapy 5, 1
  • Consider indefinite anticoagulant therapy for patients with AT III deficiency who have had a thrombotic event 1
  • Monitor INR frequently as warfarin-protein binding may fluctuate with changing serum albumin 1

• Special considerations:

  • For patients with refractory thrombosis despite warfarin, consider LMWH as alternative 5
  • Direct oral anticoagulants (DOACs) have limited evidence in AT III deficiency 1

Important Considerations and Pitfalls

• AT III replacement options:

  • AT III concentrates (preferred for targeted replacement) 3
  • Fresh frozen plasma (FFP) or cryoprecipitate-depleted plasma contain equal quantities of AT III 6

• Monitoring effectiveness:

  • Measure AT III activity levels before and after replacement therapy
  • Target AT III activity level >80% for treatment, >120% for high-risk procedures 3
  • Monitor for signs of thrombosis despite treatment

• Common pitfalls:

  1. Failing to recognize heparin resistance as a sign of AT III deficiency 4
  2. Inadequate AT III replacement before high-risk procedures 3
  3. Not monitoring AT III levels during ECMO or other extracorporeal therapies 1
  4. Prescribing oral contraceptives to women with AT III deficiency 2

Special Situations

ECMO and Extracorporeal Therapies

• AT III deficiency can occur during ECMO support, especially in patients <1 year of age 1
• Suspect AT III deficiency if increasing heparin is needed to maintain target ACT 1
• Correct with fresh-frozen plasma or AT III supplementation 1
• Follow-up laboratory testing to confirm correction of the deficiency 1

Nephrotic Syndrome

• Consider prophylactic anticoagulation when serum albumin <20-25 g/L with additional risk factors 1
• Higher than usual heparin dosing may be required due to AT III urinary loss 1

By addressing low AT III levels promptly with appropriate replacement therapy and anticoagulation, you can significantly reduce the risk of thrombotic complications in these high-risk patients.