Antiphospholipid Syndrome: Diagnosis and Management

Garcia D, Erkan D.
Diagnosis and Management of the Antiphospholipid Syndrome. N Engl J Med 2018;May 23:[Epub ahead of print].

The following are key points to remember from this review article about the diagnosis and management of antiphospholipid syndrome (APS):

  1. APS is a systemic autoimmune disease defined by thrombotic or obstetrical events that occur in patients with persistent antiphospholipid antibodies.
  2. Antiphospholipid antibodies target β2-glycoprotein I. This suppresses the activity of tissue factor pathway inhibitor, reduces activated protein C activity, and activates complement.
  3. Thrombotic events in APS can be venous, arterial, or microvascular. Patients with catastrophic APS present with thrombosis involving multiple organs.
  4. Obstetrical APS is characterized by fetal loss after the 10th week of gestation, recurrent early miscarriages, intrauterine growth restriction, or severe preeclampsia.
  5. APS is often associated with other systemic autoimmune diseases (such as systemic lupus erythematosus); however, APS commonly occurs without other autoimmune manifestations.
  6. Not every positive antiphospholipid antibody test is clinically significant. Lupus anticoagulant testing correlates better with clinical events than anti-cardiolipin antibodies or anti-β2-glycoprotein I antibodies.
  7. The risk of thrombosis in a patient with antiphospholipid-antibody-positive testing but no prior thrombotic episodes or other risk factors (e.g., autoimmune disease) is <1% per year.
  8. Persistently positive APS requires that laboratory tests be conducted at least 12 weeks apart. A high-risk profile involves a persistently positive lupus anticoagulant independent of anti-cardiolipin or anti-β2-glycoprotein I antibody results.
  9. The use of low-dose aspirin for “primary thrombosis prevention” in patients with APS but no prior thrombosis is controversial. No other prophylactic therapy has been robustly proven effective.
  10. For patients with APS and a history of venous thrombosis, treatment with heparin and warfarin (target international normalized ratio [INR] 2-3) is recommended. Anticoagulation is usually recommended indefinitely for patients whose venous thrombosis was unprovoked.
  11. Antiphospholipid antibodies can lead to falsely elevated INR results (most common with point-of-care devices). Confirming the factor X activity (using a chromogenic assay) can be useful to calibrate the target INR range.
  12. Currently, there is insufficient evidence to support the use of direct oral anticoagulants in APS patients.
  13. Many experts recommend warfarin use for patients with APS and a history of arterial thromboses. However, patients with a history of stroke and a low-titer of anticardiolipin antibodies may be treated with aspirin alone.
  14. Early treatment is essential in catastrophic APS. This usually involves anticoagulants, steroids, intravenous immune globulin, and plasma exchange.
  15. Low-dose aspirin and therapeutic-dose heparin should be used in pregnant women with thrombotic APS, regardless of the pregnancy history. Low-dose aspirin or prophylactic-dose heparin can be used in pregnant women with APS, but no prior history of thrombosis (including 6 weeks postpartum).

Clinical Topics: Anticoagulation Management, Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism

Keywords: Antibodies, Anticardiolipin, Antibodies, Antiphospholipid, Antiphospholipid Syndrome, Anticoagulants, Aspirin, Cardiolipins, Factor X, Fetal Growth Retardation, Heparin, Immunoglobulins, Intravenous, Lupus Coagulation Inhibitor, Lupus Erythematosus, Systemic, Point-of-Care Systems, Postpartum Period, Pre-Eclampsia, Pregnancy, Protein C, Primary Prevention, Risk Factors, Stroke, Thromboplastin, Thrombosis, Thromboembolism, Venous Thrombosis, Vascular Diseases, Warfarin

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