Antiphospholipid antibodies (aPL) are autoantibodies that target phospholipid-binding proteins and are used to detect antiphospholipid syndrome (APS).
Antiphospholipid syndrome is an autoimmune disorder characterized by:
- Thrombosis: This can be venous, arterial, or microvascular. Common manifestations include deep vein thrombosis, pulmonary embolism, and stroke.
- Pregnancy complications: This includes recurrent miscarriages, especially in the second and third trimesters, preterm births due to eclampsia or severe pre-eclampsia, and placental insufficiency.
To diagnose APS, both clinical (thrombosis or pregnancy morbidity) and laboratory criteria must be met. The laboratory criteria involve the presence of antiphospholipid antibodies. These antibodies include:
- Lupus anticoagulant (LA): Detected by coagulation assays.
- Anticardiolipin antibodies (aCL): Detected by enzyme-linked immunosorbent assays (ELISA).
- Anti-β2 glycoprotein I antibodies: Also detected by ELISA.
For a diagnosis of APS, one or more of these antibodies should be present in the blood on two or more occasions at least 12 weeks apart.
In addition to APS, elevated levels of antiphospholipid antibodies can also be seen in:
- Systemic lupus erythematosus (SLE) and other autoimmune diseases.
- Infections like syphilis, HIV, hepatitis C, etc.
- Certain medications, such as chlorpromazine, quinidine, and phenytoin.
- Elderly individuals, without any apparent associated disease or condition.
It’s crucial to interpret the results in the clinical context, as the presence of these antibodies alone (without clinical manifestations) does not confirm a diagnosis of APS.
Management
The management of antiphospholipid syndrome (APS) primarily focuses on reducing the risk of thrombosis and managing complications associated with the syndrome, such as pregnancy morbidity. The specific treatment plan depends on the individual’s clinical presentation and associated risk factors.
- Thrombotic APS (Patients with a history of thrombosis)
- Venous or Arterial Thrombosis: Lifelong anticoagulation is generally recommended. The most commonly used anticoagulant is warfarin (with a target INR of 2.0 to 3.0 for venous thrombosis). Direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, and dabigatran are being investigated for use in APS but are not routinely recommended for APS patients with arterial thrombosis or those who are positive for lupus anticoagulant due to concerns over efficacy and safety in these subgroups.
- Recurrent Thrombosis while on Anticoagulation: Some patients may require a higher INR target (e.g., 3.0 to 4.0) or the addition of low-dose aspirin.
- Obstetric APS (Patients with pregnancy morbidity)
- Low-risk (history of early miscarriage only): Treatment with low-dose aspirin and possibly heparin (usually low molecular weight heparin like enoxaparin) during pregnancy.
- High-risk (history of late miscarriage, preterm birth due to preeclampsia, or previous placental insufficiency): Both low-dose aspirin and heparin are recommended throughout the pregnancy.
- Close monitoring during pregnancy with frequent obstetric ultrasounds is crucial.
- Primary Prophylaxis (Patients with aPL antibodies but no history of thrombosis or pregnancy morbidity)
- The decision to initiate primary prophylaxis in asymptomatic aPL-positive individuals depends on the presence of other risk factors for thrombosis. For those with additional risk factors (e.g., hypertension, smoking, oral contraceptive use), low-dose aspirin may be considered.
- Catastrophic APS (CAPS)
- CAPS is a rare and severe form of APS leading to multiorgan failure due to widespread microthromboses. It requires aggressive treatment, including high-dose anticoagulation, corticosteroids, plasma exchange, and intravenous immunoglobulin (IVIG). Rituximab or eculizumab may also be considered for refractory cases.
- Other Considerations
- Patients with APS should be counseled on lifestyle modifications to reduce thrombotic risk, including smoking cessation, blood pressure control, and avoiding estrogen-containing contraceptives.
- For patients undergoing surgical procedures, careful perioperative management of anticoagulation is necessary to balance the risk of thrombosis against the risk of bleeding.
- Vaccinations: There is no established guideline suggesting that APS patients should avoid any particular vaccine, including COVID-19 vaccines. Patients with APS should follow the same vaccination guidelines as the general population.
The treatment of APS requires a multidisciplinary approach, often involving rheumatologists, hematologists, obstetricians, and other specialists, tailored to the individual patient’s clinical presentation and needs.