Hematology Oncology · Year 2 · from Hematology Oncology

Case 2: Antiphospholipid Syndrome

Patient Presentation

Demographics: 32-year-old female

Chief Complaint: Left leg swelling and history of recurrent pregnancy losses

History of Present Illness: The patient presents with 4 days of progressive left leg swelling and pain. She has a history of three first-trimester pregnancy losses and one stillbirth at 24 weeks gestation. She had a "blood clot" 5 years ago in her arm associated with a central line during hospitalization for pneumonia, for which she received 3 months of anticoagulation. She is otherwise healthy and takes no medications.

Physical Examination:

  • Vital signs: BP 125/78, HR 84, RR 16, Temp 36.9C
  • General: Healthy-appearing woman
  • Cardiovascular: Regular rhythm, no murmurs
  • Left leg: Pitting edema to knee, calf tenderness, positive Homan's sign
  • Right leg: Normal
  • Skin: Livedo reticularis pattern on lower extremities

Workup and Results

Compression Ultrasound:

  • Left popliteal and posterior tibial vein thrombosis confirmed

Coagulation Studies:

  • PT/INR: 12.5 sec / 1.0
  • aPTT: 52 sec (prolonged; normal 25-35)
  • Mixing study: Does NOT correct (46 sec after mix)

Antiphospholipid Antibody Panel:

  • Lupus anticoagulant: Positive (dRVVT ratio 2.1)
  • Anticardiolipin IgG: 85 GPL (high positive; normal <20)
  • Anti-beta-2-glycoprotein I IgG: 78 SGU (high positive)

Additional Labs:

  • ANA: Positive 1:80 (low titer)
  • Anti-dsDNA: Negative
  • CBC: Normal

Clinical Image

Clinical photograph demonstrating livedo reticularis, a lace-like violaceous skin pattern commonly seen in antiphospholipid syndrome, resulting from microvascular blood flow abnormalities.

Diagnosis

Antiphospholipid Syndrome (Primary)

Diagnostic criteria met:

  • Clinical criteria: Vascular thrombosis (2 events) AND obstetric morbidity (recurrent early losses, one late fetal loss)
  • Laboratory criteria: Triple-positive (LA, aCL, anti-B2GPI all positive)
  • Confirmation required: Repeat testing at 12+ weeks to confirm persistence

Treatment Plan

  1. Acute DVT treatment:
  • Therapeutic anticoagulation with warfarin (INR target 2.0-3.0)
  • Bridge with LMWH until INR therapeutic for 2 days
  • Note: DOACs are generally NOT recommended for APS (especially triple-positive)
  1. Duration:
  • Indefinite anticoagulation given:
  • Recurrent thrombosis
  • Triple-positive antibodies (highest risk)
  • Obstetric APS
  1. Future pregnancy management:
  • When pregnancy desired: LMWH + low-dose aspirin throughout pregnancy
  • Close obstetric monitoring
  • Avoid warfarin in pregnancy (teratogenic)
  1. Confirm diagnosis:
  • Repeat antiphospholipid antibodies at 12+ weeks
  • Must remain positive to confirm diagnosis
  1. Lupus evaluation:
  • Monitor for development of SLE (currently no criteria met)

Teaching Points

  1. APS is characterized by thrombosis AND/OR pregnancy morbidity with persistent antiphospholipid antibodies
  2. Lupus anticoagulant prolongs aPTT in vitro but causes thrombosis in vivo (paradox)
  3. Triple-positive patients (all 3 antibody types) have highest thrombosis risk
  4. Warfarin is preferred over DOACs for APS, especially if triple-positive or arterial events
  5. Laboratory diagnosis requires positivity on 2 occasions at least 12 weeks apart
  6. Catastrophic APS is rapid-onset multi-organ failure requiring urgent plasmapheresis and anticoagulation
  7. Primary APS occurs without underlying disease; secondary APS is associated with SLE or other autoimmune conditions

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