Antiphospholipid Antibody Syndrome

Antiphospholipid Antibody Syndrome is a topic covered in the 5-Minute Clinical Consult.

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Basics

Description

Antiphospholipid antibody syndrome (APS) is an autoantibody-mediated thrombophilic disorder characterized by recurrent arterial or venous thrombosis and/or recurrent fetal loss in the presence of antiphospholipid antibodies (APAs). The APAs enhance clot formation by interacting with phospholipid-binding plasma proteins. The resulting APS can cause morbidity and mortality in both pregnant and nonpregnant individuals:

  • Types of APS (based on clinical presentation)
    • Primary: occurs without associated underlying disease
    • Secondary: associated with autoimmune diseases (systemic lupus erythematosus [SLE] is most common); transient APAs linked to certain infections, drugs, and malignancies.
    • Catastrophic APS (CAPS) a.k.a. Asherson syndrome (<1%)
      • Most severe form of disease; characterized by thrombotic microangiopathy and associated with multiorgan failure
      • High mortality if treatment is delayed
      • Severe thrombocytopenia, hemolytic anemia, and DIC are additional features.
    • Associated clinical manifestations: livedo reticularis, cardiac valvular disease, thrombocytopenia, nephropathy, hemolytic anemia, coronary artery disease, and cognitive impairment
Pregnancy Considerations
  • Complications include maternal thrombosis (stroke, venous thromboembolism [VTE]), fetal death, preeclampsia and placental insufficiency, fetal growth retardation, and preterm birth.
  • Low-dose aspirin and low-molecular-weight heparin (LMWH) or unfractionated heparin are the drugs of choice in pregnancy.
  • Prophylactic-dose heparin is recommended in the postpartum period (unless patient is on therapeutic anticoagulation) given high risk of thrombosis during this time. With adequate treatment, >70% of patients with APS deliver viable infants.

Epidemiology

  • The prevalence of APAs increases with age but is not necessarily associated with a higher risk of thrombosis.
  • For APS, female > male

Incidence
  • In patients with positive APAs without prior risk of thrombosis, the annual incident risk of thrombosis is 0–3.8%. This risk is up to 5.3% in those with triple positivity (anticardiolipin antibodies, lupus anticoagulant [LAC], and anti–β2-glycoprotein-1 (GP1) antibodies positive).
  • 10–15% of recurrent abortions are attributable to APS.

Prevalence
APAs are present in 1–5% of the general population and in ~40% of those with SLE. A higher prevalence is seen in those with VTE and stroke.

Etiology and Pathophysiology

  • Anti–β2-GP1 antibodies play a central role in the pathogenesis of APS. The procoagulant effect is mediated by various possible mechanisms:
    • Endothelial effects: inhibition of prostacyclin production and loss of annexin V cellular shield
    • Platelet activation resulting in adhesion and aggregation
    • Interference of innate anticoagulant pathways (such as inhibition of protein C)
    • Complement activation
  • Pregnancy-related complications are also a result of autoantibody-mediated effects:
    • Interference with expression of trophoblastic adhesion molecules resulting in abnormal placentation and placental thrombosis
  • Proposed mechanisms: excess production of natural antibodies, molecular mimicry due to infections, exposure of phospholipid antigens during platelet activation, cardiolipin peroxidation, and genetic predisposition
  • A “second hit” by environmental factors may be required to produce thrombosis.

Genetics
Most cases of APS are acquired. There are a few studies of familial occurrence of anticardiolipin antibodies and LAC. A valine 247/leucine polymorphism in β2-GP1 could be a genetic risk for the presence of anti–β2-GP1 antibodies and APS.

Risk Factors

  • Age >55 years in males, >65 years in females
  • Cardiovascular risk factors (hypertension, diabetes, obesity, smoking, combined oral contraceptive use)
  • Underlying autoimmune disease (SLE, rheumatoid arthritis, collagen vascular disease, Sjögren syndrome, idiopathic thrombocytopenic purpura, Behçet syndrome)
  • Surgery, immobilization, pregnancy

General Prevention

Risk factor modification: Control HTN and diabetes; smoking cessation; avoidance of oral contraceptives in high-risk patients; start thromboprophylaxis in established cases.

Commonly Associated Conditions

  • Autoimmune diseases: SLE (most common), scleroderma, Sjögren syndrome, dermatomyositis, and rheumatoid arthritis
  • Malignancy
  • Infections: viral, bacterial, parasitic, and rickettsial
  • Certain drugs associated with APA production without increased risk of thrombosis: phenothiazines, hydralazine, procainamide, and phenytoin
  • Hemolysis, elevated liver enzymes, and low platelet count in association with pregnancy (HELLP) syndrome
  • Sneddon syndrome (APS variant syndrome with livedo reticularis, HTN, and stroke)

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Citation

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TY - ELEC T1 - Antiphospholipid Antibody Syndrome ID - 116896 Y1 - 2019 PB - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116896/all/Antiphospholipid_Antibody_Syndrome ER -