Antiphospholipid Antibody Syndrome

Aka: Antiphospholipid Antibody Syndrome, Antiphospholipid Syndrome, Lupus Anticoagulant Disorder, APLA

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II. Pathophysiology

  1. Antiphospholipid Antibodies bind cell membrane phospholipids (including vascular endothelium)
    1. Antibody binding triggers inflammatory and prothrombotic changes
  2. Increases risk of recurrent thrombosis of any size vessel
    1. Core features include arterial thrombosis, venous thrombosis and Recurrent Pregnancy Loss
  3. Highly associated with Systemic Lupus Erythematosus (SLE)
    1. However, 60% of cases are not related to SLE

III. Risk Factors

  1. Rheumatologic Conditions
    1. Systemic Lupus Erythematosus (40% of cases)
    2. Rheumatoid Arthritis (20% of RA patients are APLA positive)
  2. Genetic predisposition
    1. Inherited Coagulopathy
    2. Various HLA markers
  3. Infections
    1. HIV Infection
    2. Leptospira
    3. Lyme Disease
    4. Syphilis
  4. Medications
    1. Chlorpromazine
    2. Phenytoin
    3. Procainamide
    4. Quinidine
  5. Other factors
    1. Recurrent Pregnancy Loss (20% are APLA positive)

IV. Associated Conditions

  1. Major clinical associations
    1. Venous thrombosis
      1. Deep Vein Thrombosis
      2. Pulmonary Embolism
    2. Arterial thrombosis
      1. Cerebrovascular Accident (CVA)
      2. Transient Ischemic Attacks
      3. Myocardial Infarction
      4. Gangrene
    3. Recurrent Pregnancy Loss
    4. Thrombocytopenia
    5. Hemolytic Anemia
  2. Other clinical associations
    1. Heart Valve abnormality (esp. mitral and aortic valves)
    2. Positive Coombs tests
    3. Livedo Reticularis
    4. Migraine Headaches
    5. Leg ulcers
    6. Myelopathy
    7. Chorea
    8. Pulmonary Hypertension
    9. Avascular necrosis

V. Labs

  1. Antiphospholipid Antibodies (APLA)
    1. Background
      1. Up to 10% of healthy patients are APLA positive at low titers
        1. However persistently high titers occur in less than 1% of healthy patients
      2. APLA positive status is based on at least 1 of 3 markers positive
        1. Positive tests should be confirmed with a second test at >=12 weeks after inital test
        2. Risk increases with the number of positive markers
    2. Anticardiolipin Antibody IgG and IgM (most sensitive test)
      1. IgG > 20 GPL is positive (>40 GPL are associated with increased thrombotic events)
      2. IgM > 20 MPL units is positive
      3. Possibly IgA positive
    3. Anti-B2-Glycoprotein I Autoantibodies
    4. Lupus Anticoagulant (most specific test, but Test Sensitivity only 20%)
  2. Other lab findings
    1. Partial Thromboplastin Time (PTT) prolonged
    2. Autoantibodies are present in 5% of healthy patients
    3. False PositiveVDRL (30-40%)
    4. Cytopenias
      1. Thrombocytopenia
      2. Anemia

VI. Diagnosis: Revised Sapporo Criteria (2006)

  1. Diagnosis requires at least 1 clinical AND 1 lab criteria
  2. Clinical Criteria (at least one required)
    1. Vascular Thrombosis (one or more events)
      1. Arterial thrombosis OR
      2. Deep Vein Thrombosis (but NOT Superficial Thrombophlebitis) OR
      3. Small vessel thrombosis
    2. Recurrent Pregnancy Loss
      1. Unexplained fetal death at >10 weeks OR
      2. Premature birth <34 weeks due to PIH or placental insufficiency OR
      3. Three of more serial Spontaneous Abortions <10 weeks without other cause (e.g. chromosomal, anatomic, hormonal)
  3. Lab Criteria
    1. At least 1 of 3 Positive APLA (at high titers) by two tests spaced at least 12 weeks apart

VII. Prevention: Thrombotic Complications

  1. Anticoagulation
    1. Warfarin
      1. Moderate to high dose (INR >2 to 3) is protective
      2. Low dose (INR <1.9) does not prevent thrombosis
    2. Low Molecular Weight Heparin (LMWH)
      1. May be used for APLA in pregnancy
    3. Aspirin
      1. Protects against pregnancy loss (in those with multiple losses)
      2. Does not protect against thrombosis
  2. Systemic Lupus Erythematosus and APLA positive
    1. Hydroxychloroquine
    2. Consider Aspirin prophylaxis
  3. Avoid factors predisposing to thrombosis
    1. Avoid Oral Contraceptive use
    2. Avoid Immobility
  4. Modify atherosclerotic risk factors
    1. Hyperlipidemia
    2. Tobacco Abuse
    3. Diabetes Mellitus

VIII. Complications

  1. See Associated Conditions above
  2. Catastrophic Anti-Phospholipid Antibody Syndrome (CAPS)

IX. Resources

  1. Not So Benign Antiphospholipid Antibody Syndrome (Hematologist)
    1. https://doi.org/10.1182/hem.V21.1.2024112

X. References

  1. Bustamante (2023) Antiphospholipid Syndrome, StatPearls, Treasure Island, FL [PubMed]
    1. https://www.ncbi.nlm.nih.gov/books/NBK430980/
  2. Levine (2002) N Engl J Med 346:752-63 [PubMed]

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