Antiphospholipid syndrome

Overview

Antiphospholipid Syndrome (APS) is an autoimmune disorder characterized by the presence of antibodies that target phospholipids, components of cell membranes, leading to increased risk of blood clots in veins and arteries. APS can cause complications such as deep vein thrombosis (DVT), stroke, recurrent pregnancy loss, and other clotting-related conditions. It may occur on its own (primary APS) or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE).

APS affects individuals of all ages but is more common in women, particularly of childbearing age.

Causes

APS is caused by the immune system mistakenly producing antiphospholipid antibodies, which attack proteins bound to phospholipids on cells. The three main antibodies associated with APS are:

• Anticardiolipin antibodies (aCL)

• Lupus anticoagulant (LA)

• Anti-beta-2 glycoprotein I antibodies

The exact reason these antibodies develop is not fully understood. Possible contributing factors include:

• Genetic predisposition

• Infections (e.g., viral or bacterial)

• Certain medications (e.g., hydralazine, phenytoin)

• Other autoimmune conditions

Symptoms

Symptoms of APS can vary depending on which part of the body is affected by abnormal clotting. Common manifestations include:

Thrombotic Events:

• Deep vein thrombosis (DVT): Swelling and pain in the legs

• Pulmonary embolism (PE): Shortness of breath, chest pain

• Stroke or transient ischemic attacks (TIA): Sudden numbness, weakness, or speech difficulties

• Arterial thrombosis: May cause heart attack or limb ischemia

Obstetric Complications:

• Recurrent miscarriages, especially in the second or third trimester

• Preeclampsia or eclampsia

• Preterm birth due to placental insufficiency

Other Possible Symptoms:

• Livedo reticularis (mottled skin pattern)

• Headaches or migraines

• Seizures or cognitive dysfunction (rare)

• Thrombocytopenia (low platelet count)

Diagnosis

Diagnosis of APS is based on both clinical and laboratory criteria, established by the updated Sapporo (Sydney) classification criteria. Requirements include:

Clinical Criteria:

• At least one documented episode of vascular thrombosis

• History of pregnancy morbidity (e.g., ≥3 early miscarriages, ≥1 late miscarriage, or premature birth due to placental complications)

Laboratory Criteria (at least one must be present on two occasions ≥12 weeks apart):

• Positive lupus anticoagulant

• Positive anticardiolipin antibody (IgG or IgM)

• Positive anti-beta-2 glycoprotein I antibody (IgG or IgM)

Additional tests like Doppler ultrasound, echocardiography, or brain imaging may be used to assess clotting damage.

Treatment

Treatment for APS focuses on preventing blood clots and managing associated complications. Main approaches include:

Anticoagulation Therapy:

• Warfarin (Coumadin): Long-term blood thinner for patients with prior thrombosis

• Heparin and low-dose aspirin: Often used during pregnancy to reduce miscarriage risk

• Direct oral anticoagulants (DOACs): May be used in some cases but not yet standard for APS

Immunosuppressive Therapy:

• Used in patients with APS associated with lupus or other autoimmune diseases

Lifestyle Modifications:

• Avoid smoking and estrogen-containing contraceptives

• Manage cardiovascular risk factors (e.g., hypertension, cholesterol, diabetes)

Prognosis

With proper treatment and monitoring, many individuals with APS can lead normal, productive lives. However, APS is a lifelong condition with risks of recurrent clotting and pregnancy complications. Key points about prognosis include:

• Recurrent thrombosis risk remains high without anticoagulation

• Women with APS can have successful pregnancies with appropriate management

• Catastrophic APS (CAPS), a rare form involving multiple organ thrombosis, has a high mortality rate and requires aggressive treatment

Long-term follow-up with a hematologist or rheumatologist is often necessary to manage the condition and adjust therapy as needed.