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Updated: Dec 24 2019

Antiphospholipid Syndrome

  • Snapshot
    • A 30-year-old woman presents to the physician's office for evaluation of recurrent fetal losses. She reports having had 3 past spontaneous abortions at <10 weeks of gestational age. She also reports having a history of deep venous thromboses. She denies ever being diagnosed with systemic lupus erythematosus but has been diagnosed with thyroid disease. Physical exam is remarkable for livedo reticularis on her thighs. Further blood testing reveals positive lupus anticoagulant and anticardiolipin antibody.
  • Introduction
    • Clinical definition
      • autoimmune disorder that is often associated with systemic lupus erythematosus (SLE), characterized by thromboses and recurrent spontaneous abortions
    • Epidemiology
      • incidence
        • increases with age
      • demographics
        • female > male
        • affects adults
      • risk factors
        • SLE
        • drugs
          • procainamide
          • isoniazid
          • hydralazine
          • oral contraceptives
          • malignancy
    • Pathogenesis
      • autoantibodies (lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein antibodies) react against platelet membranes or prothrombin-platelet membrane complex, activating endothelial cells and platelets
        • which further activates complement-mediated thrombosis
    • Associated conditions
      • SLE
      • other autoimmune diseases
      • preeclampsia or eclampsia
    • Prognosis
      • risk of recurrence is high
  • Presentation
    • Symptoms
      • recurrent fetal loss
      • symptoms related to thrombosis site
        • dyspnea
        • abdominal discomfort
        • neurologic symptoms
        • chest pain
        • skin rash
    • Physical exam
      • cutaneous findings include livedo reticularis
        • reticular (lacy) or mottled violaceous rash
  • Studies
    • Labs
      • lupus anticoagulant
        • prolonged dilute Russell viper venom time (DRVVT) test
        • prolonged partial thromboplastin time (PTT)
      • anti-β2 glycoprotein (IgG and IgM)
      • anticardiolipin (IgG and IgM)
      • coagulation studies
        • normal or slightly prolonged prothrombin time
        • normal bleeding time
        • normal platelet count
      • false positives due to antibodies
        • + VDRL/RPR due to anticardiolipin antibodies
        • prolonged PTT due to lupus anticoagulant
          • not corrected by adding normal platelet-free plasma
    • Making the diagnosis
      • based on clinical presentation and laboratory studies
      • diagnostic criteria includes ≥ 1 clinical and ≥ 1 laboratory criteria
        • clinical
          • thrombosis
          • spontaneous abortion at ≥ 10 weeks gestational age
          • premature birth at < 35 weeks gestational age due to eclampsia, pre-eclampsia, or placental insufficiency
          • ≥ 3 spontaneous abortions before < 10 weeks gestational age
        • laboratory
          • lupus anticoagulant
          • anticardiolipin antibody
          • anti-β2 glycoprotein
  • Differential
    • Factor V Leiden mutation
      • distinguishing factor
        • absence of antibodies
    • Antithrombin deficiency
      • distinguishing factor
        • normal PTT
  • Treatment
    • Medical
      • warfarin
        • indications
          • for non-pregnant patients
          • prevention of thrombosis
          • target INR 2-3
      • aspirin plus unfractionated heparin
        • indications
          • for pregnant patients
          • prevention of pregnancy loss
  • Complications
    • Fetal loss
    • Stroke
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