Antiphospholipid Syndrome - APS

Antiphospholipid Syndrome - APS

 

Antiphospholipid syndrome (APS) is an autoimmune disorder in which the body makes antibodies against its own phospholipids or plasma proteins. APS is characterized by thrombosis, fetal loss or both and associated with persistent levels of antiphospholipid (aPL) antibodies.

Epidemiology

  • Prevalence
    • Unknown in general population for APS
    • Lupus anticoagulant (LA) antibodies affect 2-4% of the population and also occur in numerous conditions, particularly autoimmune diseases, thrombocytopenia and neurological disorders
  • Age – 20s-50s most commonly
  • Sex – female predominance

Risk Factors

  • Presence of an autoimmune disease

Pathophysiology

  • The presence of antiphospholipid (aPL) antibodies is a risk factor for vascular thrombosis and pregnancy-related morbidity
    • Antiphospholipid antibodies represent a heterogeneous group of autoantibodies that recognize various phospholipids (PL), PL-binding plasma proteins, and/or PL-protein complexes
  • APL antibodies are present in as many as 50% of people with systemic lupus erythematosus (SLE) and in varying prevalences in the rest of the population
  • Lupus anticoagulants (LA) are autoantibodies that target complexes of phospholipids with either Beta-2 glycoprotein 1 (ß2GP1) or clotting factors such as prothrombin
    • LA are also a risk factor for vascular thrombosis
    • Thrombosis occurs in about 5-20% of all patients with LA
      • Recurrent thrombotic episodes can occur

Clinical Presentation and Diagnosis

Revised Classification Criteria for the Antiphospholipid Antibody Syndrome

For antiphospholipid antibody syndrome to be discussed, at least 1 clinical and 1 laboratory criterion must be met.
Clinical criteria

Vascular thrombosis: One or more clinical episodes of arterial, venous, or small-vessel thrombosis in any tissue or organ, which must be validated by imaging studies or histopathology.

Pregnancy morbidity:

  • One or more unexplained deaths of a morphologically normal fetus beyond the 10th week of gestation or
  • One or more premature births of a morphologically normal neonate before the 34th week of gestation due to preeclampsia, eclampsia, or placental insufficiency or
  • Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.
Laboratory criteria

(Each must be present on 2 or more occasions at least 12 weeks apart.)

Lupus Anticoagulant: Detected in plasma according to the guidelines of the International Society on Thrombosis and Hemostasis.

Anticardiolipin antibody: IgG and/or IgM isotype present in a medium or high titer (> 40 GPL or MPL or > the 99th percentile), measured by a standardized ELISA.

Anti-ß2 glycoprotein I antibody: IgG and/or IgM isotype in high titer (> 99th percentile), measured by a standardized ELISA.
GPL, IgG phospholipid antibobdy; MPL, IgM phospholipid antibody; ELISA, enzyme-linked immunosorbent assay.
Adapted from Miyakis S et al. J Thromb Haemost. 2006.

 

  • Other indications may also include endocarditis, stroke, heart attack, livedo reticularis, thrombocytopenia and hemolytic anemia
  • Some of the antibodies detected in the following tests may be present in APS but occur in association with either LA or aCL or ß2GP1 (IgG and/or IgM) antibodies
    • The presence of IgA antibodies alone are non-diagnostic and are not recommended in the workup of APS
    • Assays not recommended for the definitive diagnosis of APS
      • Cardiolipin IgA antibody
      • Beta-2 glycoprotein 1 Antibody, IgA
      • Phosphatidylserine Antibodies, IgG, IgM, and IgA
      • Prothrombin Antibody, IgG and IgM 

Differential Diagnosis

  • Hypercoagulable state
  • Pregnancy loss
  • Autoimmune disease
  • Drugs

Treatment

  • Treatment of lupus anticoagulants reduces recurrent pregnancy loss

See Also