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Updated: Dec 18 2021

Antiphospholipid Syndrome

  • Snapshot
    • A 40-year-old woman with systemic lupus erythematosus presents for evaluation of recurrent deep venous thromboses. In the past year, she has had 5 events. On further questioning, she also reveals a history of having 2 spontaneous abortions at > 10 weeks gestation. Today, her physical exam is unremarkable. Blood testing reveals a positive antinuclear antibody and lupus anticoagulant. She is started on anticoagulation.
  • Introduction
    • Clinical definition
      • an autoimmune disorder, 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
  • ETIOLOGY
    • Pathogenesis
      • autoantibodies (lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein antibodies) react against platelet membranes or prothrombin-platelet membrane complex, activating endothelial cells and platelets
        • this activates complement-mediated thrombosis
    • Associated conditions
      • SLE
      • other autoimmune diseases
      • preeclampsia or eclampsia
  • 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
  • Differential
    • Factor V Leiden mutation
      • distinguishing factor
        • absence of antibodies
    • Antithrombin deficiency
      • distinguishing factor
        • normal PTT
  • 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
  • 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
  • Prognosis
    • Risk of recurrence is high
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