Snapshot A 30-year-old Caucasian man presents with sudden shortness of breath. He denies any recent long train or plane rides, but endorses a history of multiple DVTs. A Doppler ultrasound shows a small DVT in his left calf. His complete blood count is normal. His PT and PTT are also normal. He is started on LMWH with the intention of bridging to warfarin. A few days later, his activated protein C resistance assay comes back positive for a factor V Leiden mutation. Overview Introduction Hypercoagulable state/thrombophilia from mutated factor V Epidemiology Most common cause of inherited hypercoagulable states Most common in Caucasians etiology Pathogenesis review of anticoagulation pathway protein C (with protein S as a co-factor) inactivates factors V and VIII mutated factor V lacks cleavage site for activated protein C factor V remains active in coagulation pathway defective anticoagulation thrombosis Genetics factor V Leiden mutation incomplete autosomal dominant heterozygous → risk of thrombosis homozygous → higher risk of thrombosis Presentation Symptoms/physical exam most common DVT, recurrent less common PE central retinal vein occlusion hepatic vein thrombosis if pregnant higher risk of miscarriage STUDIES Normal PT/PTT Differential Diagnosis Protein C/S deficiency Malignancy HIT Antiphospholipid syndrome Antithrombin deficiency presents with no change in PTT with heparin administration treat with direct thrombin inhibitor (or very high dose heparin) followed by warfarin Diagnosis Activated protein C resistance assay (factor V Leiden specific functional assay) if positive, confirm with DNA testing Treatment Prevention avoid external causes of hypercoagulability OCPs hormone replacement therapy If thrombosis LMWH bridge to warfarin If pregnant, give thromboprophylaxis LMWH warfarin contraindicated Long-term antithrombotic therapy not recommended Complications Miscarriage Thrombosis Prognosis Mortality not affected