Antiphospholipid Syndrome (APS) or Antiphospholipid Antibody Syndrome (APLS)

Antiphospholipid syndrome (APS) is an autoimmune disease caused by antiphospholipid antibodies. It triggers blood clot formation (thrombosis) in both arteries and veins and leads to pregnancy complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia. Diagnosis requires a clinical presentation (e.g., thrombosis or pregnancy complications) and two positive serology results (e.g., detection of anti-β2-glycoprotein-I antibodies in blood) at least three months apart.

APS can be classified as primary or secondary. Primary APS occurs without associated diseases, while secondary APS is linked to autoimmune conditions such as systemic lupus erythematosus (SLE). In rare cases, APS causes generalized thrombosis, leading to sudden organ failure, a condition known as catastrophic antiphospholipid syndrome (CAPS), which is associated with a high mortality risk.

Treatment for APS typically involves anticoagulants like heparin to reduce the risk of thrombosis and improve pregnancy outcomes. Warfarin is avoided during pregnancy because, unlike heparin, it crosses the placenta and is teratogenic.

Clinical Features

APS can cause arterial or venous blood clots in any organ system or lead to pregnancy-related complications. In APS patients:

• Deep vein thrombosis (DVT) of the lower extremities is the most common venous event.
• Stroke is the most common arterial event.
• Pregnant women with APS face risks such as recurrent miscarriages, intrauterine growth restriction (IUGR), and preterm births, often caused by placental infarction.

In some cases, APS appears to impair trophoblast differentiation under the influence of antiphospholipid syndrome (aPL), leading to fetal growth or developmental issues. In particular, APS plays a significant role in miscarriages during the second and third trimesters, often in combination with SLE.

Additional Findings

Other common features, though not part of the diagnostic criteria, include:

• Thrombocytopenia (low platelet count)
• Heart valve disease
• Livedo reticularis (a mottled, net-like discoloration of the skin)

There is also evidence of aPL antibodies being associated with headaches, migraines, and psychiatric conditions, with some studies detecting these antibodies in the blood and cerebrospinal fluid of affected patients.

Pathophysiology

In APS, antiphospholipid syndrome —produced due to autoimmune processes—are implicated in thrombosis and vascular diseases. A subset of anticardiolipin antibodies inhibits protein C, while lupus anticoagulant (LAC) binds to prothrombin, converting it into its active form, thrombin.

The syndrome can be categorized as:

• Primary APS: Occurs without underlying conditions.
• Secondary APS: Associated with autoimmune diseases, particularly SLE.

A small proportion of primary APS patients may later develop lupus.

Diagnostic Criteria

APS diagnosis is based on laboratory findings and clinical presentations, including:

• Documented arterial, venous, or capillary thrombosis—excluding superficial vein thrombosis—in any tissue or organ, without significant inflammation of the vessel wall.
• Pregnancy-related complications, such as:

One or more unexplained fetal deaths of a morphologically normal fetus (confirmed via ultrasound or direct examination) after 10 weeks of gestation.

Three or more unexplained consecutive miscarriages before 10 weeks of gestation.

At least one premature birth before 34 weeks of gestation due to eclampsia, severe preeclampsia, or placental insufficiency.

Epidemiology

APS is more common in women than men, as with many autoimmune diseases. Although the exact cause remains unknown, hypercoagulation is a hallmark.

This condition requires close monitoring and management, especially during pregnancy, to reduce complications and improve outcomes.