Antiphospholipid syndrome

What is antiphospholipid syndrome?

Antiphospholipid syndrome is an acquired autoimmune disorder characterised by recurrent arterial or venous thrombosis and/or pregnancy losses, in the presence of persistently elevated levels of anticardiolipin antibodies and/or evidence of circulating lupus anticoagulant (these abnormalities are detected by blood tests). Antiphospholipid syndrome can be primary or secondary.

• Primary antiphospholipid syndrome occurs when there is no evidence of associated diseases.
• Secondary antiphospholipid syndrome is associated with an underlying disease, usually systemic lupus erythematosus, and drugs, including levamisole-adulterated cocaine.

Seronegative antiphospholipid-like syndrome is a similar disease where antiphospholipid antibodies are not detected.

What is the cause of thrombosis in antiphospholipid syndrome?

The mechanisms resulting in a hypercoagulable state and recurrent thrombosis are not yet defined. Complement activation is involved. The 'two-hit' theory has associated the onset of thrombosis with increasing age, hypertension, diabetes, obesity, smoking, pregnancy, surgery, and other genetic hypercoagulable states.

Who gets antiphospholipid syndrome?

Antiphospholipid syndrome is generally diagnosed in young to middle-aged adults. However, it can affect children and adults of all ages.

Secondary antiphospholipid syndrome is more common in females than in males, most likely because systemic lupus erythematosus and other connective tissue disorders have a female predominance.

Patients have a history of spontaneous miscarriage, deep vein thrombosis (DVT), pulmonary embolism, myocardial infarction, or stroke.

What are the signs and symptoms of antiphospholipid syndrome?

To classify as antiphospholipid syndrome a patient must have at least one of the two following clinical manifestations in addition to the presence of certain laboratory abnormalities.

1. Venous or arterial thrombosis: this may involve the cerebral vascular system, coronary arteries, pulmonary emboli or thromboses, hepatic or renal veins, ocular veins or arteries
2. Recurring miscarriages or premature births: patients may have pre-eclampsia in pregnancy and babies may be unexpectedly small

 

Splinter haemorrhages 

Cholesterol emboli 

Other symptoms are not part of the classification criteria.

Skin disorders in antiphospholipid syndrome

Livedo reticularis affects up to 80% of people with antiphospholipid antibodies. Other features include:

• Splinter haemorrhage (one or more red or black streaks on a nail)
• Leg ulcers, both arterial and venous ulcers
• Superficial thrombophlebitis
• Blue toe syndrome
• Vasculitis involving medium-sized and small vessels

Neurological defects in antiphospholipid syndrome

• Migraine headaches
• Seizures
• Stroke
• Multi-infarct dementia

Cardiac abnormalities in antiphospholipid syndrome

• Heart murmur
• Cardiac valve vegetations

Eye disorders in antiphospholipid syndrome

• Blindness

Blood abnormalities in antiphospholipid syndrome

• Thrombocytopenia (low platelet count)
• Haemolytic anaemia (low red cell count due to the destruction of the cells by antibodies)

Catastrophic antiphospholipid syndrome refers to blockage of blood vessels in multiple organs, which may occur over days or weeks. The condition is serious and often lethal.

How is antiphospholipid syndrome diagnosed?

The antiphospholipid syndrome has various clinical manifestations and is associated with a range of autoantibodies. In 2006, revised criteria for the diagnosis of antiphospholipid syndrome stated that at least one clinical criterion and one laboratory criterion must be present [1]. The name 'lupus anticoagulant' is misleading because not all patients with a positive result have systemic lupus erythematosus, and the antiphospholipid syndrome is associated with increased blood clotting rather than increased bleeding.

Laboratory tests detect antiphospholipid antibodies or abnormalities in phospholipid-dependent tests of blood clotting (coagulation). Patients with suspected antiphospholipid syndrome should be tested for the following:

• aCL antibodies
• Anti-beta-2 glycoprotein I antibodies
• Activated partial thromboplastin time (aPTT)
• LA tests such as dilute Russell viper venom time (DRVVT)
• Syphilis (false-positive serology)
• Complete blood cell count (thrombocytopenia, Coombs-positive haemolytic anaemia)

What treatment is available for antiphospholipid syndrome?

The main aim of treatment is to prevent the clinical manifestations of antiphospholipid syndrome. Risk factors for thrombosis should be identified and removed or corrected:

• Encourage smoking cessation
• Avoid oral contraceptives
• Identify and treat high blood pressure and elevated blood fats.

Antiplatelet drugs such as low-dose aspirin may be useful.

There is no specific treatment for antiphospholipid syndrome. Signs and symptoms are treated as they occur. For example, thrombosis or embolism is treated with the anticoagulants heparin and warfarin.