Diagnosis and Treatment of Antiphospholipid Syndrome (APS) and Covid
Article: Antiphospholipid Antibodies and COVID-19: A Systematic Review of Clinical Implications
https://onlinelibrary.wiley.com/doi/10.1002/iid3.70134
Gist:
This systematic review examines the link between antiphospholipid antibodies (aPL) and COVID-19, analyzing 59 studies with 28,489 patients. Over half (50.84%) of COVID-19 patients tested positive for aPL, with a 38.55% prevalence in those with thrombosis. The findings suggest a potential role of aPL in COVID-19-related thrombotic events, highlighting the need for further research to understand clinical implications and improve management strategies. Limitations include variability in study designs and methodologies, emphasizing the need for standardized approaches in future studies.
Antiphospholipid syndrome (APS) and hormonal imbalances—particularly involving estrogen and cortisol—can significantly influence the course of APS, especially in women. Estrogen, which is present in birth control pills and hormone replacement therapy, can heighten the risk of clot formation in individuals with APS. As a result, these medications are generally avoided in people with the condition. Cortisol, a hormone associated with the body’s stress response, may also be affected by APS. In some cases, this can lead to adrenal insufficiency, further complicating the disease.
APS is diagnosed based on a combination of clinical criteria (symptoms or events like thrombosis or pregnancy complications) and laboratory findings (specific antibodies).
Diagnosis of APS
1. Clinical Criteria:
- Thrombosis:
- At least one documented episode of venous, arterial, or small-vessel thrombosis. Common examples include:
- Venous thrombosis: Deep vein thrombosis (DVT), pulmonary embolism.
- Arterial thrombosis: Stroke, transient ischemic attack (TIA), or myocardial infarction.
- At least one documented episode of venous, arterial, or small-vessel thrombosis. Common examples include:
- Pregnancy complications:
- Recurrent early miscarriages (≥3 unexplained before 10 weeks).
- At least one unexplained fetal death after 10 weeks of gestation.
- Severe preeclampsia or placental insufficiency leading to premature delivery (<34 weeks).
2. Laboratory Criteria:
- The presence of at least one of the following antiphospholipid antibodies (aPL) on two or more occasions, at least 12 weeks apart:
- Lupus anticoagulant (LA): Interferes with clotting in vitro but is associated with a hypercoagulable state in vivo.
- Anticardiolipin antibodies (aCL): IgG or IgM at moderate to high titers.
- Anti-β2 glycoprotein I antibodies (anti-β2GPI): IgG or IgM.
Both clinical and lab criteria must be met for a definitive diagnosis of APS.
Catastrophic APS (CAPS):
- A rare, life-threatening variant of APS involving multi-organ thrombosis over a short period. It’s a medical emergency.
Treatment of APS
Treatment aims to prevent thrombosis, manage pregnancy risks, and address complications like catastrophic APS. Management is tailored to the type of APS (primary or secondary) and patient-specific factors.
1. Thrombosis Prevention and Management:
- Acute Thrombosis:
- Treated with anticoagulants (e.g., low-molecular-weight heparin [LMWH] or unfractionated heparin) followed by long-term therapy with warfarin.
- Warfarin is titrated to maintain an INR (international normalized ratio) of 2.0–3.0. In high-risk cases (e.g., recurrent thrombosis), the INR target may be 3.0–4.0.
- Prophylaxis:
- In asymptomatic APS patients without thrombosis, aspirin (low dose, 81–100 mg daily) may be considered if risk factors are present.
- Pregnant women with APS typically receive a combination of low-dose aspirin and LMWH to prevent miscarriage.
2. Treatment During Pregnancy:
- APS poses significant risks for pregnancy, such as recurrent miscarriages, preeclampsia, or fetal growth restriction.
- Management includes:
- Low-dose aspirin and LMWH throughout pregnancy and postpartum.
- Close monitoring with frequent ultrasounds to assess fetal growth and placental function.
3. Catastrophic APS (CAPS):
- A medical emergency requiring aggressive treatment, including:
- Anticoagulation: Intravenous heparin.
- High-dose corticosteroids: To reduce inflammation.
- Plasmapheresis or intravenous immunoglobulin (IVIG): To remove antiphospholipid antibodies.
- Sometimes, cyclophosphamide is used if associated with lupus (SLE).
4. Managing Underlying Conditions:
- In secondary APS (APS associated with another autoimmune disease like lupus), the underlying condition is treated (e.g., hydroxychloroquine and steroids in lupus).
What should you avoid with APS (Antiphospholipid Syndrome)?
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Foods rich in vitamin K (especially if you're taking warfarin):
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Avoid or limit large amounts of foods high in vitamin K, such as:
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Avocados
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Broccoli
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Brussels sprouts
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Cabbage
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Leafy greens (spinach, kale, etc.)
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Chickpeas
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Why? Vitamin K can interfere with warfarin, a common blood thinner used in APS.
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Alcohol:
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Alcohol can increase the blood-thinning effect of warfarin, raising the risk of bleeding.
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Always ask your doctor whether to limit or avoid alcohol completely.
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Medications and supplements:
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Be cautious with over-the-counter painkillers like ibuprofen and aspirin—they also thin the blood and can cause bleeding when combined with blood thinners.
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Talk to your doctor about any medication or supplement you're taking, even herbal products.
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Why is Eliquis (Apixaban) not recommended for APS?
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Eliquis (Apixaban) and other DOACs (Direct Oral Anticoagulants), like:
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Dabigatran (Pradaxa)
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Edoxaban (Lixiana)
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Rivaroxaban (Xarelto)
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These are not recommended for patients with APS, especially those at high risk (e.g., with triple antibody positivity), because:
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Studies have shown an increased risk of recurrent blood clots (thrombotic events) in APS patients using DOACs compared to warfarin.
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Can you take Ibuprofen with APS?
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Use with caution:
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Ibuprofen and similar drugs (NSAIDs) may thin the blood slightly.
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If you're already on a blood thinner, taking NSAIDs may increase the risk of bleeding.
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Always consult your doctor before using painkillers.
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What is APS Type 1 (Autoimmune Polyglandular Syndrome Type 1)?
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A rare autoimmune disorder caused by mutations in the AIRE gene.
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Inherited in an autosomal recessive manner.
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Characterized by a triad of symptoms:
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Chronic mucocutaneous candidiasis (persistent fungal infections on skin and mucous membranes)
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Hypoparathyroidism (low calcium levels due to underactive parathyroid glands)
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Adrenal insufficiency (Addison’s disease)
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Over 60 mutations in the AIRE gene are known to cause APS Type 1.
Lifestyle Modifications:
- Avoid risk factors for thrombosis:
- Smoking cessation.
- Maintaining a healthy weight.
- Managing other conditions like diabetes or hypertension.
- Avoid oral contraceptives containing estrogen (they increase clotting risk).
Future Therapies
Research is exploring alternatives to warfarin, such as direct oral anticoagulants (DOACs) like rivaroxaban or apixaban, although these are not yet standard for APS. In addition, therapies targeting the immune system (e.g., rituximab or complement inhibitors) are under investigation.
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