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Antiphospholipid Syndrome – Causes, Symptoms & Treatment

Antiphospholipid syndrome (APS) is an autoimmune disorder causing abnormal blood clotting and pregnancy complications due to specific antibodies targeting the body's own proteins.

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Antiphospholipid syndrome (APS) is an autoimmune disorder causing abnormal blood clotting and pregnancy complications due to specific antibodies targeting the body's own proteins.

What is Antiphospholipid Syndrome?

Antiphospholipid syndrome (APS) is an acquired autoimmune disorder in which the immune system mistakenly produces antibodies against certain phospholipid-binding proteins in the blood. These antibodies increase the risk of abnormal blood clot formation in arteries and veins, as well as pregnancy-related complications such as recurrent miscarriages and preeclampsia. APS can occur as a standalone condition (primary APS) or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE) (secondary APS).

Causes

The exact cause of APS is not yet fully understood. It involves a misdirected immune response in which the body produces antibodies against its own phospholipid-associated proteins. The most clinically relevant antibodies include:

Lupus anticoagulant
Anticardiolipin antibodies (aCL)
Anti-beta-2 glycoprotein I antibodies (ß2GPI)

Known risk and triggering factors include:

Genetic predisposition
Other autoimmune diseases (e.g., SLE, rheumatoid arthritis)
Certain infections (e.g., HIV, hepatitis C, Lyme disease)
Certain medications (e.g., hydralazine, phenytoin)

Symptoms

Symptoms of APS are mainly caused by the increased tendency for blood clot formation. Common manifestations include:

Deep vein thrombosis (DVT): Blood clots in the deep veins, most often in the legs
Pulmonary embolism: A blood clot blocking a pulmonary blood vessel
Stroke or transient ischemic attacks (TIA)
Heart attack in younger patients without classical cardiovascular risk factors
Pregnancy complications: Recurrent miscarriages, stillbirth, preterm birth, and preeclampsia
Livedo reticularis: A net-like, bluish-purple discoloration of the skin
Thrombocytopenia (low platelet count)

In rare and severe cases, catastrophic APS (CAPS) can develop, characterized by rapid multiorgan failure due to widespread microvascular thrombosis.

Diagnosis

The diagnosis of APS is based on a combination of clinical features and laboratory findings. According to the internationally recognized Sapporo criteria (revised in 2006), both a clinical criterion and a laboratory criterion must be fulfilled:

Clinical Criteria

At least one documented thrombotic event in an artery, vein, or small vessel
One or more pregnancy losses after the 10th week of gestation, three or more consecutive early miscarriages before the 10th week, or a premature birth before the 34th week due to preeclampsia or placental insufficiency

Laboratory Criteria

Detection of lupus anticoagulant, anticardiolipin antibodies, or anti-ß2GPI antibodies at medium to high levels
The finding must be confirmed on two separate occasions at least 12 weeks apart

Additional tests such as a full blood count, coagulation studies, and imaging procedures (e.g., ultrasound, MRI) may be used to assess complications.

Treatment

The primary goal of treatment is to prevent further thrombotic events and manage existing complications. Therapy is tailored to the individual risk profile of each patient.

Anticoagulation (Blood Thinning)

Heparin and vitamin K antagonists (e.g., warfarin, phenprocoumon) are the standard treatment after confirmed thrombosis
The intensity of anticoagulation (target INR) depends on the type and location of the thrombotic event
Direct oral anticoagulants (DOACs) may be used in certain cases but are generally not recommended as first-line therapy for high-risk APS

Treatment During Pregnancy

Combination of low-molecular-weight heparin and low-dose aspirin to reduce pregnancy loss
Close monitoring by specialist physicians throughout pregnancy

Treatment of Catastrophic APS (CAPS)

Intensive care management
High-dose anticoagulation, corticosteroids, intravenous immunoglobulins, and plasmapheresis

General Measures

Avoiding additional risk factors such as smoking, estrogen-containing contraceptives, and prolonged immobility
Regular follow-up appointments with a specialist

Prognosis

With consistent treatment and regular monitoring, many patients with APS can lead largely normal lives. However, the risk of recurrent thrombosis remains elevated, often requiring long-term or lifelong anticoagulation therapy. Early diagnosis and close medical follow-up are essential for a favorable prognosis.

References

Miyakis S. et al. – International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). Journal of Thrombosis and Haemostasis, 2006.
Devreese K. M. J. et al. – Antiphospholipid antibodies and the antiphospholipid syndrome: Pathogenesis, diagnosis, and treatment. Seminars in Thrombosis and Hemostasis, 2023.
European League Against Rheumatism (EULAR) – Recommendations for the management of antiphospholipid syndrome in adults, 2019.

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