Lupus Anticoagulants

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Investigate unexplained blood clots (DVT, PE, stroke)

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Lupus Anticoagulants - Comprehensive Medical Test Guide

Why is it done?
- Detects antiphospholipid antibodies that prolong clotting time in vitro, increasing thrombotic risk in vivo
- Evaluates patients with unexplained thrombosis (deep vein thrombosis, pulmonary embolism, arterial clots)
- Investigates recurrent miscarriages or fetal loss in pregnant women
- Assesses prolonged activated partial thromboplastin time (aPTT) that does not correct with normal plasma mixing
- Screens for antiphospholipid syndrome in patients with systemic lupus erythematosus (SLE) or SLE-like disorders
- Performed when patients present with thrombotic events, particularly at young age or without typical risk factors
- Part of diagnostic workup for antiphospholipid syndrome diagnosis (requires positive result on two occasions ≥12 weeks apart)
Normal Range
- Negative Result (Normal): Lupus anticoagulant is not detected; aPTT ratio typically <1.2 (normal range varies by laboratory but usually 0.80-1.20 ratio or 24-40 seconds depending on methodology)
- Positive Result (Abnormal): Lupus anticoagulant is detected; aPTT ratio typically >1.2 or significantly prolonged, with failure to normalize on mixing study (indicates presence of inhibitor not deficiency)
- Mixing Study (Confirmatory): Patient plasma mixed 1:1 with normal pooled plasma; lack of correction indicates lupus anticoagulant presence (inhibitor pattern) vs. factor deficiency (would correct)
- Silica Clotting Time (dRVVT): Ratio typically <1.2 is normal; ratio >1.2 suggests lupus anticoagulant; ratio >2.0 strongly suggests positive result
- Units: Reported as ratio, seconds, or simply positive/negative; values expressed as patient plasma aPTT divided by normal plasma aPTT
- Interpretation: Normal = absent lupus anticoagulant (does not indicate normal clotting); Abnormal = presence of lupus anticoagulant antibodies (paradoxically causes bleeding in vivo despite prolonged in vitro clotting)
Interpretation
- Positive Lupus Anticoagulant: Indicates presence of antiphospholipid antibodies; significantly increases thrombotic risk (venous and arterial); paradoxically prolongs in vitro clotting time while promoting in vivo thrombosis
- Negative Lupus Anticoagulant: Suggests absence of lupus anticoagulant; other causes of aPTT prolongation should be investigated (factor deficiencies, other inhibitors, anticoagulation therapy)
- Borderline/Weak Positive: May indicate low-level lupus anticoagulant; repeat testing recommended; clinical correlation essential
- Clinical Significance of Positive Results: Diagnosis of antiphospholipid syndrome requires positive result on ≥2 occasions ≥12 weeks apart plus clinical events (thrombosis or pregnancy morbidity); single positive result requires confirmation
- Factors Affecting Results:
- Warfarin or other anticoagulants may interfere; heparin can cause false positives; lupus anticoagulant may fluctuate over time; transient positivity possible with infections or medications; platelet count <100,000 may affect test accuracy
- Associated Conditions with Positive Results: Antiphospholipid syndrome (primary or secondary to SLE); systemic lupus erythematosus; recurrent thrombosis; recurrent pregnancy loss; thrombocytopenia; hemolytic anemia; livedo reticularis
- Thrombotic Risk Assessment: High-titer lupus anticoagulant (strongly positive) carries greater thrombotic risk than low-titer; triple positivity (lupus anticoagulant plus anticardiolipin and anti-β2-GPI antibodies) indicates highest risk
Associated Organs
- Primary Organ Systems Affected:
- Vascular system (primary): Both venous and arterial circulation affected; deep vein thrombosis most common venous manifestation; arterial thrombosis less common but serious
- Reproductive system: Placental insufficiency leading to recurrent pregnancy loss, intrauterine growth restriction, preeclampsia, eclampsia, and fetal complications
- Central nervous system: Stroke, transient ischemic attacks, migraine, cognitive dysfunction, chorea
- Hematologic system: Thrombocytopenia, hemolytic anemia, coagulation abnormalities
- Pulmonary system: Pulmonary embolism, pulmonary hypertension, acute respiratory distress syndrome
- Associated Diseases and Conditions:
- Primary antiphospholipid syndrome (APS): Thrombotic disease without underlying autoimmune disorder
- Secondary APS: Associated with systemic lupus erythematosus (most common), Sjögren syndrome, rheumatoid arthritis, scleroderma, antiphospholipid syndrome with other autoimmune diseases
- Catastrophic antiphospholipid syndrome (CAPS): Rare life-threatening form with multiple simultaneous thrombotic events
- Chronic infections (HIV, hepatitis C, syphilis) can induce lupus anticoagulant
- Malignancy-associated antiphospholipid antibodies
- Potential Complications of Positive Results:
- Recurrent thrombotic episodes (venous thromboembolism, arterial thrombosis) often requiring long-term anticoagulation
- Reproductive complications: Infertility, recurrent miscarriages, preeclampsia, fetal loss, prematurity
- Organ damage from chronic anticoagulation or thrombotic events
- Hemorrhagic complications if anticoagulation therapy is necessary (bleeding risk)
- Development of catastrophic APS (fulminant thrombosis in multiple organs) if untreated
Follow-up Tests
- Confirmatory Testing (if initial positive):
- Repeat lupus anticoagulant test 12-24 weeks after initial positive result (required for APS diagnosis); confirmation establishes persistent antibodies
- Mixing study with normal plasma to confirm inhibitor pattern
- Complementary Antiphospholipid Antibody Testing:
- Anticardiolipin (aCL) antibodies (IgG and IgM): Independent marker of APS; often present concurrently
- Anti-β2-glycoprotein-I (anti-β2-GPI) antibodies: Third criterion for APS diagnosis; may be isolated marker
- Associated Autoimmune Screening:
- Antinuclear antibodies (ANA) and specific SLE antibodies (anti-dsDNA, anti-Smith): To diagnose secondary APS associated with SLE
- Complement levels (C3, C4): Assess autoimmune activity
- Extractable nuclear antigens (ENA panel): Sjögren's syndrome antibodies (SSA/Ro, SSB/La), other connective tissue disease markers
- Coagulation Panel Studies:
- Prothrombin time (PT) and International Normalized Ratio (INR): Baseline for anticoagulation monitoring
- Fibrinogen level: Assess overall coagulation status
- Platelet count: Evaluate for thrombocytopenia associated with APS
- D-dimer: Rule out acute thrombosis if clinically indicated
- Imaging Studies (when indicated):
- Duplex ultrasound of lower extremities: To evaluate for deep vein thrombosis in positive patients with symptoms
- CT pulmonary angiography (CTPA): To assess for pulmonary embolism if clinically suspected
- MRI/CT brain: Evaluate neurological manifestations (stroke, TIA) if present
- Monitoring Frequency for Positive Results:
- Initial: Repeat lupus anticoagulant 12-24 weeks to confirm diagnosis (once positive, may repeat annually or as clinically indicated)
- Anticoagulation: INR monitoring every 2-4 weeks initially, then monthly to quarterly if on warfarin; periodic CBC, PT/INR assessment
- Pregnant patients with APS: Baseline testing at first prenatal visit, then serial monitoring as clinically indicated (typically monthly)
- Post-thrombotic event: Baseline coagulation studies, then periodic monitoring based on anticoagulation therapy type and patient stability
- Serial Antibody Testing:
- May repeat anticardiolipin and anti-β2-GPI antibodies to establish persistence and assess thrombotic risk stratification
Fasting Required?
- Fasting Requirement: No fasting required for lupus anticoagulant test
- General Preparation:
- Patient can eat and drink normally before the test
- No special preparation needed beyond standard venipuncture requirements
- Medications and Anticoagulation:
- Anticoagulation therapy (warfarin, DOACs, heparin): Should NOT be stopped prior to testing; report current anticoagulation status to laboratory
- Heparin therapy: Can cause false positive results; unfractionated heparin can be reversed with protamine if necessary before testing for accurate results
- All current medications should be reported to the laboratory and healthcare provider
- Sample Collection Requirements:
- Blood sample collected via venipuncture into citrated tube (blue-top tube with specific anticoagulant)
- Proper fill volume critical (specific ratio of blood to anticoagulant); underfilled or overfilled tubes invalidate results
- Sample should be inverted 4-5 times immediately after collection to ensure proper mixing
- Transport to laboratory promptly; room temperature preferred; some labs may require cool transport
- Processing typically within 1-2 hours of collection for optimal accuracy
- Special Circumstances:
- Severe thrombocytopenia (<20,000 cells/μL): May require correction or adjustment; notify laboratory
- Lupus anticoagulant most reliably detected when aPTT is prolonged; best timing is when patient not on heparin
- Multiple specimens may be collected to perform different coagulation studies simultaneously
- Patient education: Inform phlebotomist of bleeding disorders, anticoagulation therapy, or recent transfusions

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