Antiphospholipid antibody syndrome

Antiphospholipid Antibody Syndrome (Antiphospholipid antibody syndrome, APS)

1) Disease Description (Causes and Symptoms)

• Definition summary: An autoimmune thrombotic disease characterized by a tendency to develop blood clots within blood vessels and recurrent pregnancy loss, associated with the presence of antiphospholipid antibodies such as lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies.
• Summary of causes/pathophysiology:
  • The exact cause is unknown. Antiphospholipid antibodies activate vascular endothelial cells and platelets and stimulate the coagulation system and complement, thereby promoting thrombosis and inhibiting fibrinolysis.
  • Thrombosis in placental blood vessels can impair placental function and lead to recurrent miscarriage and preterm birth.
• Main symptoms:
  • Venous thrombosis, particularly deep vein thrombosis of the lower extremities and pulmonary embolism; arterial thrombosis, such as stroke and transient cerebral ischemia
  • Recurrent spontaneous miscarriage, fetal death, and preterm birth, associated with preeclampsia and placental insufficiency
  • Thrombocytopenia, heart valve abnormalities, and abnormalities of the kidneys, liver, skin, and central nervous system, among others
• Diagnostic summary:
  • Both clinical criteria, such as thrombosis or a pregnancy-related history, and laboratory criteria, such as positive antiphospholipid antibodies, must be met.
  • Antibodies must be confirmed as positive at least twice, generally at an interval of 12 weeks or more.
  • Main tests: lupus anticoagulant testing, anticardiolipin IgG/IgM, and anti-β2-GPI IgG/IgM.

2) Treatment Methods and Precautions

• Basic principles:
  • In cases of isolated antibody positivity without clinical symptoms, such as thrombosis or pregnancy complications, active anticoagulant treatment is generally not given. However, preventive treatment may be considered in high-risk cases, such as triple-positive antibodies, high titer, or the presence of triggering factors including surgery, prolonged bed rest, or the postpartum period.
• Anticoagulant treatment:
  • When acute thrombosis is present: low-molecular-weight heparin (LMWH) or intravenous heparin, followed by switching to oral warfarin, a vitamin K antagonist. The standard recommended treatment duration is generally applied; for example, a single episode of unprovoked venous thrombosis requires at least 3 months, while long-term therapy may be considered for recurrent or unprovoked thrombosis and antiphospholipid antibody positivity.
  • Warfarin target INR:
    • Standard recommendation: For most cases of venous thrombosis, the target INR is 2.0–3.0.
    • In cases of recurrent arterial thrombosis or recurrence, high-intensity treatment, such as an INR of 3.0 or higher, may be considered, but individualization is necessary.
  • Direct oral anticoagulants (DOACs): Not recommended for patients with triple-positive APS or a history of arterial thrombosis; increased risk of recurrence has been reported in clinical trials. Use of DOACs should be decided cautiously under the judgment of a specialist.
• Pregnancy-related management:
  • During pregnancy: Warfarin should be avoided because of the risk of fetal malformations, particularly during the first trimester. During pregnancy, low-molecular-weight heparin, at a prophylactic or therapeutic dose, is generally recommended in combination with low-dose aspirin.
  • Delivery and postpartum period: Because the risk of thrombosis increases after childbirth, a postpartum anticoagulation strategy, such as LMWH for a certain period or resumption of warfarin, is necessary.
• Management in preventive situations:
  • Temporary preventive anticoagulation, such as LMWH, is recommended in cases involving surgery, prolonged bed rest, long-distance travel, or a risk of obstetric complications.
• Severe form (catastrophic APS, CAPS):
  • In cases of rapidly developing, multiorgan thrombosis that are high-risk and life-threatening: combine anticoagulation with heparin, high-dose steroids, and plasma exchange or IVIG. If necessary, immunosuppressants such as cyclophosphamide and complement-targeted treatment such as eculizumab may be considered.
• Lifestyle management and general precautions:
  • Do not smoke; actively manage cardiovascular risk factors, including weight, blood pressure, diabetes, and lipid levels.
  • Oral estrogen preparations, including oral contraceptives, increase the risk of thrombosis, so alternative contraceptive methods are recommended.
  • During anticoagulant treatment, manage the risk of trauma and bleeding and be cautious about drug interactions.
• Complications:
  • Stroke, myocardial infarction, pulmonary embolism, chronic kidney damage, including renal vein thrombosis, and catastrophic APS, involving multiple organ failure.
• Monitoring:
  • Regular monitoring is necessary during anticoagulant use, including INR for warfarin, platelet count, kidney function when heparin/LMWH dose adjustment is necessary, and obstetric follow-up during pregnancy.

3) Checklist Before an Outpatient Visit (Including Items to Bring and Example Questions)

• Items to bring to the appointment
  • A list of all medications currently being taken, including prescription drugs, OTC drugs, supplements, and herbal medicines, along with the times and doses taken
  • Reports or summaries of previous thrombosis-related tests and imaging results, such as ultrasound, CT, MRI, and previous INR records
  • Previous antiphospholipid antibody test results, including the test type, date, and value, and the interpretation date if the result was positive
  • A record of recent symptoms, such as thrombosis symptoms, bleeding, history of miscarriage, and pregnancy history, including when the symptoms began and how they progressed
  • If planning a pregnancy or currently pregnant, the gestational age and obstetric records
• Information to check in advance for the outpatient visit
  • Whether there has been recent surgery, hospitalization, prolonged bed rest, or a long-distance flight
  • Family history, including thrombosis and inherited thrombophilia
• Items for the patient to record and bring
  • Whether leg pain or swelling, shortness of breath, chest pain, or neurological symptoms, such as hemiplegia or speech impairment, have occurred within the past 3 months
  • Menstrual, pregnancy, and childbirth history
• Tests and preparations that may be requested from the doctor in advance
  • Current antibody tests, including lupus anticoagulant, anticardiolipin, and anti-β2-GPI, and baseline blood tests, including platelet count and kidney function
  • If necessary, imaging for diagnosing thrombosis, such as deep vein ultrasound and CT/CTA

4) Examples of General Questions to Ask the Doctor

• "When do I need to start and stop anticoagulant treatment in my case? What should my target INR be?"
• "What are the main side effects of this medication, warfarin/heparin/aspirin, and what precautions should I take?"
• "I am pregnant or planning a pregnancy. What anticoagulation strategy do you recommend?"
• "How should I prepare for life events such as surgery, dental treatment, pregnancy, or travel?"
• "What lifestyle change should I make first to reduce the risk of recurrent thrombosis?"

5) Examples of Disease-Specific Questions

• If planning a pregnancy:
  • "Based on my current antiphospholipid antibody test results, including the type and value, what anticoagulation regimen, including the dose and duration, do you recommend during pregnancy?"
• If surgery or a procedure is scheduled:
  • "How should I manage anticoagulant interruption and bridging before and after the upcoming surgery or procedure? Which is more concerning in my case, the risk of bleeding or the risk of thrombosis?"

Note: The diagnosis and treatment plan vary depending on the individual patient's medical history, antibody profile, including single or combined positivity and antibody titer, history of thrombosis, and pregnancy status. Specific management should be determined in consultation with a specialist, such as a hematologist, rheumatologist, or obstetrician-gynecologist.