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Updated: Mar 16 2018

Antithrombin III Deficiency

  • Snapshot
    • A 23-year-old girl presents to the emergency room with shortness of breath, pleuritic chest pain, and hemoptysis. She is found to be tachycardic; her pulse is 102/min. She has a history of DVTs requiring heparin at age 20. However, she has not been on any maintenance therapy. Clinical suspicion for a pulmonary embolism is high, and a chest spiral CT scan is ordered. The CT shows a saddle embolism. Heparin is started immediately.
  • Introduction
    • Pathogenesis
      • hypercoagulable state/thrombophilia due to deficiency in antithrombin III
        • antithrombin III, an anticoagulant
          • inhibits primarily thrombin (factor IIa) and factor Xa
          • also inhibits activated factors VII, IX, XI, and XII
          • remember, heparin enhances activity of antithrombin
        • deficiency causes defect in anticoagulation pathway
    • Genetics
      • autosomal dominant inheritance
    • Risk factors
      • liver disease (antithrombin III is synthesized in the liver)
      • renal failure/nephrotic syndrome (loss of proteins in urine)
      • heparin use (causes acquired reduction in antithrombin level)
  • Presentation
    • Symptoms/physical exam
      • may be asymptomatic
      • thrombosis at a young age (venous > arterial)
        • DVT
        • PE
  • Evaluation
    • Normal PT, PTT, and thrombin time
    • Reduces the increase in PTT following heparin administration
    • Heparin cofactor assay, an antithrombin functional assay
      • ↓ antithrombin activity
  • Differential Diagnosis
    • HIT
    • Protein C/S deficiency
    • Factor V Leiden mutation
  • Treatment
    • For acute thrombosis
      • heparin
    • For maintenance therapy
      • bridge to warfarin
    • Medical therapy
      • antithrombin replacement therapy
        • peripartum and perioperative
  • Prognosis, Prevention, and Complications
    • Prognosis
      • at risk of thromboembolism
        • lifetime risk 50-85%
    • Prevention
      • avoid pro-coagulant states
        • OCPs
        • hormone replacement therapy
    • Complications
      • related to thromboembolism
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