AntiPhosphoLipid Syndrome - Abu-Shakra

Question 1

What are the assays that test for anti-phospholipid (aPL) syndrome?

Answer 1

1. Anti-Cardiolipin Elisa
   -Anti-Anti-aPL antibodies, show color if positive
   -Problematic because will be positive in 80% of normal population.
   -30-40% of SLE patients will be positive but only 10-15% have aPL features
   -Sensitive but not specific, better for screening
   -IgG, IgM (pathogenic), IgA (not diagnostic)
   -Done first because:
   • 80% of patients with LAC have aCL
   • 20% of patients with aCL have LAC
2. Lupus Anti-coagulant
   - Add reagent to the blood to alter the coagulation cascade
   - 30% of SLE patients are positive, less sensitive but increased clinical association (50% of SLE patients with +LAC develop thrombosis within 20 years)
   - Test will show increased PPT (despite thrombophilia) because of serum interaction with the test, unlike with bleeding diseases, adding normal serum won’t slow the PPT but adding PL will
3. Anti-beta-2-Glycoprotein I
   - Becoming the major secondary test

50% are +ANA

Question 2

What is the pathogenesis of antiphospholipid syndrome?

Answer 2

• -ve charged PL (phosphatidylserine)
migrate from inner to outer cell membrane.
• GPI binds phosphatidylserine (themselves, then Ab bind complex)
• APL binds GPI-PL and initiate a signaling
cascade that induces tissue factor expression
causing platelet aggregation and thrombosis

Question 3

What is the treatment of anti-phospholipid syndrome?

Answer 3

Asymptomatic
○ If there are high titers that are there for a long period of time, you treat with low-dose of aspirin (but not evidence based)
○ Low titer: won’t do anything
○ If SLE give aspirin + antimalarials

• Thrombosis
○ Give warfarin
○ With the first venous thrombosis, we want INR: 2-3
 More high intensity
○ With recurrent venous thrombosis or arterial thrombosis, we want INR>3 and give warfarin for life

• For skin rash, livedo, you don’t use anything to treat
• Valve nodule or leg ulcers: can give warfarin for anti-coagulation

• Treat only severe thrombocytopenia (PLT<50,000) with steroids

Question 4

What is catastrophic antiphospholipid syndrome (CAPS) and what are its criteria?

How is CAPS managed?

Answer 4

1. Multiple vascular occlusion of small vessels affecting 3 or more internal organs. (Kidney, heart, lung, brain, liver)
2. Simultaneous onset or in less than 1 week.
3. Confirmation by histology of small vessels occlusion.
4. Positive aCL, LAC.

Look very sick, usually intubated

• Thrombocytopenia
• Develop after major infection, surgery, or withdrawal of anti-coagulant therapy (or post-partum)
• Identify triggering factor (Infection)
• IVIG
• Plasma-pheresis
• High doses of corticosteroids
• Heparin

50-60% chance of mortality