Antiphospholipid syndrome is an autoimmune condition, where autoantibodies are formed that target the glycoprotein of circulating phospholipids and endogenous coagulative and anti-coagulative proteins. This results in thromboembolism and pregnancy complications in females. All ages can be affected, but most diagnoses occur between the ages 20 and 50 years. Females are more commonly affected, as seen in other autoimmune conditions, although pregnancy-related symptoms are likely to increase diagnosis in this sex.
This article will describe the aetiology and presentation of antiphospholipid syndrome, and how the condition is investigated, diagnosed and treated.
Aetiology
Antiphospholipid autoantibodies are thought to be produced in response to a combination of genetic, hormonal and environmental factors, although these are not known. Some factors identified to increase risk include:
- a family member with antiphospholipid syndrome
- some HLA genotypes (ie. HLA- B8, DR2, DR3, DR4 and DR7)
- viral infection (ie. cytomegalovirus, parvovirus B19)
- bacterial infection (ie. E. coli, leptospirosis)
- medicines (ie. anti-epileptic agents, oral contraceptives)
- poor lifestyle (ie. high cholesterol intake, limited exercise, smoking, obesity)
The condition can be primary or secondary, when it occurs alongside other autoimmune conditions such as systemic lupus erythematosus (SLE) or rheumatoid arthritis.
Clinical Assessment
The two main symptoms of antiphospholipid syndrome fall under two categories:
- increased clotting, most commonly deep vein thrombosis (DVT), pulmonary embolism (PE) and stroke. Other potential thrombosis complications include high blood pressure, transient ischaemic attack (TIA), pulmonary embolism, retinal thrombosis, although any blood vessels and organs can be affected
- adverse pregnancy outcomes, including recurrent miscarriage, preterm delivery, intrauterine growth restriction, stillbirth and severe pre-eclampsia
Some believe that this condition can cause balance and mobility problems, visual disturbance and other symptoms of multiple sclerosis (MS). However, this is controversial, as antiphospholipid antibodies can be seen in up to 5% of the normal population, including in MS patients.
Investigation of antiphospholipid syndrome should involve a thorough blood screen. This should ideally be taken when the patient is stable and before medication is commenced, and should include:
- full blood count (ie. low platelets, signs of haemolytic anaemia)
- clotting screen
- antiphospholipid antibodies
- extended thrombophilia screen, including Factor V Leiden variant, prothrombin, protein C, protein S, factor VIII, antithrombin, plasminogen and tissue plasminogen activator (TPA)
Intravascular thrombosis can be investigated through various imaging techniques, such as Doppler ultrasound, CT, MRI.
Diagnosis
Proper diagnosis is vital in order to treat this condition effectively and avoid severe complications. Diagnosis requires at least one clinical criterion and at least one laboratory criterion. Blood tests should be repeated after 12 weeks to exclude false positives.
Clinical criteria:
- 1+ confirmed arterial, venous or small vessel thrombosis
- 1+ unexplained late miscarriages (post-10 weeks gestation)
- 3+ unexplained consecutive early miscarriages (pre-10 weeks gestation)
- 1+ premature births at or before 34 weeks, due to eclampsia, severe pre-eclampsia or placental insufficiency
Laboratory criteria:
- positive anticardiolipin antibody
- positive anti-ß2 glycoprotein I antibody
- positive lupus anticoagulant
Management
Antiphospholipid syndrome causing thrombotic complications should be treated immediately with long-term prophylactic anticoagulation or low-dose antiplatelet therapy. Warfarin should be used rather than direct oral anticoagulants, with an INR target of 2-3. Warfarin is preferred over antiplatelets if the patient has shown thrombotic symptoms.
If thrombotic events persist despite the adequate anticoagulation, other medications can be considered in conjunction, including corticosteroids, plasmapheresis and rituximab.
During pregnancy, aspirin or heparin, or a more commonly a combination of both, should be used. This should continue 1 to 6 weeks postpartum. Warfarin is highly teratogenic so should be avoided.
A healthy lifestyle should be encouraged to avoid complications, including smoking cessation, balanced diet, regular exercise, weight loss and avoiding excessive alcohol intake. Diabetes, hypertension and hyperlipidaemia should be managed to reduce cardiovascular risk. The cessation of exogenous female hormone, such as the combined oral contraceptive (COCP) or hormone replacement therapy (HRT), should be considered.
Complications & Prognosis
Long-term prognosis of antiphospholipid syndrome is mainly determined by the frequency and severity of thrombosis complications. These can be in part avoided with adequate anticoagulation, which can also decrease the risk of unsuccessful pregnancy to roughly 20%. However, a small number of patients still experience complications despite extensive treatment.
Catastrophic antiphospholipid syndrome is a rare but severe complication of this syndrome, where multiple small vessel thromboses occur throughout the body, leading to multiple organ failure. It is thought to arise in response to an infection, trauma, surgery or other stressful insult. The lungs, brain and kidneys are commonly affected, causing dyspnoea, confusion, seizures and peripheral oedema. Patients require immediate hospitalisation and strong anticoagulation, but even in these circumstances, the complication carries a 50% mortality.
Summary
- Antiphospholipid syndrome is an autoimmune condition, most commonly diagnosed in women of child-bearing age
- Symptoms arise from an increased risk of thrombosis, causing DVT, PE and stroke, and adverse pregnancy outcomes, such as miscarriage and preterm labour
- Diagnosis requires one clinical criteria and a persistent positive antibody detected in the serum
- Long-term anticoagulation or antiplatelet therapy helps reduce complications, and therefore improve prognosis
Authors
Written by Paul Armitage (Medical Student)
Reviewed by Dr Bethan Myers (Consultant Haematologist)