Antiphospholipid syndrome

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
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Immune disorder leading to increased risk of blood clots

Antiphospholipid syndrome
Synonyms	Hughes syndrome, aCL syndrome, anticardiolipin antibody syndrome, lupus anticoagulant syndrome
Pronounce	N/A
Field	Immunology, Hematology, Rheumatology
Symptoms	Thrombosis, miscarriage, stroke, chronic headache, seizures, livedo reticularis
Complications	Deep vein thrombosis, pulmonary embolism, stroke, pregnancy loss, dementia
Onset	Usually young to middle adulthood
Duration	Chronic
Types	Primary, Secondary (e.g., in systemic lupus erythematosus)
Causes	Autoimmune reaction to phospholipid-binding proteins
Risks	Systemic lupus erythematosus, infections, genetic factors
Diagnosis	Antibody testing, coagulation studies, clinical criteria
Differential diagnosis	Thrombophilia, systemic lupus erythematosus, disseminated intravascular coagulation
Prevention	Risk reduction of thrombosis; monitoring during pregnancy
Treatment	Anticoagulants, low-dose aspirin, immunosuppressive therapy
Medication	Warfarin, Heparin, Aspirin, Hydroxychloroquine
Prognosis	Variable; risk of recurrence manageable with long-term treatment
Frequency	~5 per 100,000 people annually
Deaths	Associated with thrombotic events and pregnancy complications

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the presence of autoantibodies against phospholipid-binding proteins, most notably β₂-glycoprotein I and cardiolipin. These antibodies increase the risk of blood clot formation in both arteries and veins, as well as pregnancy complications such as recurrent miscarriage, stillbirth, and preeclampsia.

APS may occur as a primary condition or in association with other autoimmune diseases, particularly systemic lupus erythematosus (SLE).

Pathophysiology

APS results from an immune-mediated attack on phospholipid-protein complexes. This leads to endothelial cell activation, platelet aggregation, and impaired fibrinolysis, which together promote a hypercoagulable state. The most commonly implicated autoantibodies are:

• Lupus anticoagulant
• Anti-cardiolipin antibodies
• Anti-β₂ glycoprotein I antibodies

Signs and Symptoms

Symptoms of APS stem from thrombotic events and may include:

• Deep vein thrombosis (DVT)
• Pulmonary embolism (PE)
• Ischemic stroke
• Transient ischemic attack
• Recurrent miscarriages or stillbirth
• Livedo reticularis – a lacy purplish skin discoloration
• Thrombocytopenia
• Seizures, dementia, chorea, and other neurological disorders

Venous blood clots in legs due to Antiphospholipid syndrome.

Diagnosis

Diagnosis is based on both clinical and laboratory criteria, evaluated on two occasions at least 12 weeks apart:

• At least one clinical criterion: vascular thrombosis or pregnancy morbidity.
• At least one laboratory criterion:
  • Positive lupus anticoagulant
  • Moderate to high titers of anticardiolipin antibodies (IgG or IgM)
  • Positive anti-β₂ glycoprotein I antibodies

Diagnostic techniques include:

• Activated partial thromboplastin time (APTT)
• Dilute Russell’s viper venom time (DRVVT)
• Enzyme-linked immunosorbent assay (ELISA)
• Genetic thrombophilia screening (e.g., factor V Leiden, prothrombin G20210A, MTHFR mutation)

Types

• Primary APS: Occurs in the absence of other autoimmune conditions.
• Secondary APS: Occurs with conditions like SLE.
• Catastrophic antiphospholipid syndrome (CAPS): A rare, life-threatening variant involving widespread microvascular thrombosis.

Neurological Features

• Stroke, migraine, cognitive dysfunction, epilepsy
• Rarely: Chorea, transverse myelitis, optic neuropathy, psychosis

Obstetric Manifestations

• Recurrent first trimester miscarriages
• Intrauterine growth restriction (IUGR)
• Preterm birth due to preeclampsia or placental insufficiency

Treatment

APS is managed by preventing thrombosis and managing associated autoimmune disease:

• Anticoagulation: Warfarin, Heparin, Low molecular weight heparin
• Low-dose aspirin
• In pregnancy: Heparin and aspirin combination is preferred.
• For CAPS: Plasma exchange, glucocorticoids, intravenous immunoglobulin (IVIG)

Prognosis

With proper treatment, long-term outlook is generally favorable. Patients require lifelong monitoring, especially during pregnancy and surgical procedures. The risk of recurrence is significant if therapy is discontinued.

History

APS was first described by Dr. Graham Hughes in the early 1980s, hence its alternative name, Hughes syndrome.

See also

• Systemic lupus erythematosus
• Coagulopathy
• Thrombophilia
• Autoimmune diseases
• Pregnancy loss
• Stroke

External links

• Johns Hopkins Lupus Center – APS
• NIH – National Heart, Lung, and Blood Institute
• UpToDate – Clinical Manifestations and Diagnosis