Antiphospholipid Syndrome, Familial

Antiphospholipid Syndrome, Familial (Familial APS) is a rare autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPL) in the blood, which can lead to increased risk of blood clots, pregnancy complications, and other related symptoms. This condition is considered a familial variant of Antiphospholipid Syndrome (APS), indicating a genetic predisposition to developing these antibodies. Familial APS is distinguished from the more common, non-familial APS by its occurrence in multiple family members across generations.

Etiology

The exact cause of Familial Antiphospholipid Syndrome remains largely unknown. However, it is believed to involve a combination of genetic predisposition and environmental factors. The presence of antiphospholipid antibodies is central to the condition. These antibodies mistakenly target phospholipids, a type of fat molecule that is a normal component of cell membranes, leading to an increased risk of clot formation.

Pathophysiology

In Familial APS, the antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein I, contribute to a hypercoagulable state. This state is characterized by an increased tendency for blood clot formation, which can occur in both arteries and veins. The mechanism involves the antibodies' interference with the phospholipid-binding proteins that regulate blood clotting, leading to thrombosis.

Clinical Manifestations

The clinical manifestations of Familial APS are similar to those of the non-familial form and can vary widely among individuals. Common symptoms include:

• Deep vein thrombosis (DVT)
• Pulmonary embolism (PE)
• Stroke
• Miscarriage and pregnancy complications
• Thrombocytopenia (low platelet count)
• Livedo reticularis (a mottled purplish skin discoloration)

Diagnosis

Diagnosis of Familial APS involves a combination of clinical criteria and laboratory tests. The presence of antiphospholipid antibodies is confirmed through blood tests, typically performed on two or more occasions at least 12 weeks apart. Clinical criteria include a history of thrombosis or pregnancy morbidity. Familial occurrence of the syndrome strengthens the diagnosis.

Treatment

Treatment of Familial APS focuses on preventing thrombotic events and managing symptoms. Options include:

• Anticoagulation therapy (e.g., warfarin, heparin)
• Low-dose aspirin
• Hydroxychloroquine (for skin and joint symptoms)
• Immunoglobulin therapy (in severe cases)

Prognosis

The prognosis for individuals with Familial APS varies. With appropriate treatment, many can lead normal lives. However, the condition requires lifelong management to prevent thrombotic complications. The risk of recurrent thrombosis is high, necessitating continuous anticoagulation therapy.

Genetic Counseling

Given the familial nature of the syndrome, genetic counseling may be beneficial for affected individuals and their families. Counseling can provide information on the risk of transmission to offspring and discuss the implications of genetic testing.

See Also

• Lupus anticoagulant
• Anticardiolipin antibody
• Thrombosis
• Autoimmune diseases