antiphospholipid syndrome

The "Sticky Blood" Syndrome

Acquired autoimmune thrombophilia characterised by venous OR arterial thrombosis and/or adverse pregnancy outcomes in the presence of persistent antiphospholipid antibodies (aPL).

pathophysiology

• Target: Autoantibodies target phospholipid-binding proteins (primarily ${\beta }_2$-glycoprotein I) on endothelial cells, monocytes, and platelets.
• Mechanism: Upregulation of Tissue Factor $\to$ complement activation $\to$ systemic hypercoagulability.
• “Two-Hit” Hypothesis: aPL provides the “first hit” (primed state); a “second hit” (infection, surgery, pregnancy) triggers the event.

diagnosis (clinical framework)

Based on Revised Sapporo (Sydney) Criteria. Used for clinical diagnosis to maximize sensitivity.

clinical diagnosis vs. research classification

• Clinical Practice (Sapporo): Use these criteria. If a patient has a “high-risk profile” (e.g., Triple Positive) but doesn’t strictly meet criteria, they may still have APS.
• Research (2023 ACR/EULAR): Weighted point system. Do not use for diagnosis. It is highly specific but insensitive (misses ~20-40% of real patients, especially those with isolated IgM or lower titres).

Requirement: 1 Clinical + 1 Laboratory Criterion.

1. clinical criteria

• Vascular Thrombosis:
  • $\ge$ 1 episode of arterial, venous, or small vessel thrombosis in any tissue.
  • Must be confirmed by imaging (Doppler/CT) or histopathology.
  • Note: Includes unusual sites seen in slides (e.g., Cerebral Venous Sinus Thrombosis, Portal Vein Thrombosis, Budd-Chiari).
• Pregnancy Morbidity (One of the following):
  • $\ge$ 1 Late Loss: Fetal death $\ge 10$ weeks gestation (morphologically normal).
  • $\ge$ 1 Premature Birth: Delivery $<34$ weeks due to severe pre-eclampsia, eclampsia, or placental insufficiency.
  • $\ge$ 3 Early Losses: Spontaneous abortions $<10$ weeks (maternal/chromosomal causes excluded).

2. laboratory criteria

Must be positive on two occasions at least 12 weeks apart (to rule out transient infection-associated antibodies).

1. Lupus Anticoagulant (LA): Functional clotting assay. Strongest predictor of thrombosis.
2. Anti-Cardiolipin (aCL): IgG or IgM (Medium/High titre: $>40$ GPL/MPL or $>99$th percentile).
3. Anti-${\beta }_2$-Glycoprotein-I: IgG or IgM ($>99$th percentile).

clinical pearl: "triple positive"

Patients positive for ALL three (LA + aCL + Anti-${\beta }_2$GPI) have the highest risk of thrombosis ($>30\%$ recurrence/year) and pregnancy loss.

laboratory nuances & traps

• Lupus Anticoagulant (LA):
  • In vitro: Prolongs phospholipid-dependent clotting times (e.g., aPTT).
  • In vivo: Potent pro-thrombotic.
  • Interference: Heavily affected by anticoagulants (Heparin, DOACs, Warfarin). Do not test LA while on therapeutic anticoagulation.
• Solid Phase Assays (aCL, Anti-${\beta }_2$GPI):
  • ELISA-based.
  • Generally NOT affected by anticoagulation (can test while on Warfarin/DOAC).

management

1. venous thromboembolism (vte)

• Drug of Choice: Warfarin.
• Target: INR 2.0 – 3.0.
• Duration: Indefinite (APS is a chronic/persistent risk factor).
• DOACs?

  • contraindication: doacs

  • TRAPS Trial (2019): Rivaroxaban vs. Warfarin showed increased rates of arterial thrombosis (stroke) and major bleeding.

  • Guideline: Avoid DOACs in definitive APS, especially if triple positive or arterial history.

2. arterial thrombosis (stroke/mi)

• Drug of Choice: Warfarin.
• Target:
  • Standard: INR 2.0 – 3.0 (often combined with Aspirin).
  • Recurrent/High Risk: INR 3.0 – 4.0 (requires expert consultation).
• Secondary Prevention: Aggressive control of CV risk factors (BP, lipids).

3. pregnancy (obstetric aps)

• Standard of Care: Prophylactic LMWH + Low-dose Aspirin (ASA).
  • Start: ASA pre-conception; LMWH once pregnancy confirmed.
  • Post-partum: Continue anticoagulation for 6 weeks (high-risk period).
• Refractory Cases: Add Hydroxychloroquine or low-dose Prednisone.
• Warfarin: Teratogenic (embryopathy). Contraindicated in first trimester (6-12 weeks).

4. catastrophic aps (caps)

• Definition: “Thrombotic Storm”. Multiple organ thrombosis ($\ge 3$ organs) over <1 week.
• Mortality: High (~30%).
• Triggers: Infection, surgery, subtherapeutic INR.
• Triple Therapy Protocol:
  1. Anticoagulation: Heparin (IV UFH).
  2. Steroids: High-dose (Methylprednisolone).
  3. Removal/Exchange: Plasma Exchange (PLEX) or IVIG.

special considerations

• Isolated aPL (Carriers):
  • Positive labs but no clinical history.
  • Management: Do not anticoagulate. Address CV risk factors.
  • SLE Patients: Hydroxychloroquine reduces thrombotic risk (primary prevention).
• Thrombocytopenia:
  • Common in APS (20-40%). usually mild ($70-100\times 10^9/L$).
  • Paradox: Does not protect against thrombosis.
• Unusual Sites:
  • APS is a major cause of Budd-Chiari, Portal Vein Thrombosis, and Cerebral Venous Sinus Thrombosis.

related pages: Deep Vein Thrombosis, Pulmonary Embolism, Systemic Lupus Erythematosus, Warfarin