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