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