antiphospholipid antibody syndrome Flashcards
What is a general definition of antiphospholipid antibody syndrome?
an autoimmune condition with recurrent vascular thrombosis and/or pregnancy loss associated with persistently elevated levels of anti-phospholipid antibodies
What are the salient clinical features of anti-phospholipid antibody syndrome (manifestations, comorbidities, general treatment guidelines)
manifestations related to where the occlusion (venous/arterial) and to recurrent pregnancy losses
often comorbid with SLE (and other autoimmune diseases like RA)
for treatment, give prophylactic anticoagulation for prevention of recurrent thrombosis
give heparin and low dose aspirin during pregnancy to help the pt carry a pregnancy to term
Why is antiphospholipid antibody syndrome important?
it is the MOST frequent ACQUIRED risk factor for hypercoagulability
it is a treatable cause of pregnancy loss
How do you diagnose antiphospholipid antibody syndrome?
you need one clinical criterion AND one lab criterion
clinical: vascular thrombosis or pregnancy morbidity
Lab: lupus anticoagulant, anticardiolipin antibodies, or anti-beta2 glycoprotein. lab elevations must be consistent: true on at least 2 occasions at least 12 wks apart (though you can begin tx before waiting 12 wks if clinical and lab findings are highly suggestive, you must do confirmatory lab work)
What are important features of vascular thrombosis in anti-phospholipid antibody syndrome?
one or more episodes of arterial, venous, or small vessel thrombosis
must be confirmed by doppler or histopath
histopath biopsy must be BLAND- no evidence of inflammation in the vessel wall
What are some features of pregnancy morbidity in antiphospholipid antibody syndrome
greater than 1 spontaneous abortion after 10 wsk pregnancy with a morphologically normal fetus
or
greater than 3 unexplained sponateous abortions before 10 wks of gestation
more than 1 premature births of a morphologically normal neonate at or before 34 wks d/t severe pre-eclapsia or eclampsia or severe placental insufficiency
How do you test for lupus anticoagulant?
may see increases in prothrombin time with failure to correct the prolonged coag time by the addition of excess phospholipid and by a mixing test (mix of pt and control plasma still shows increased PTT- suggests that it isn’t due to factor deficiency)
exclude other coagulopathies like factor VIII inhibitor or heparin
Why is lupus anticoagulant a misnomer?
50% of pts with lupus anticoagulant do not have lupus
this factor prevents coagulation in vitro but is associated with hypercoagulability in vivo
What are some clinical manifestations (specific) of antiphospholipid antibody test? (7 main categories)
DVT, stroke, TIA, pulmonary embolism, (superficial thrombophlebitis), preg complications, thrombocytopenia, hemolytic anemia (rare), cardiac valve abnormalities, livedo reticularis and leg ulcers, renal disease, (GI and endocrine dysfunction)
Most important “other” manifestations: livedo reticularis, thrombocytopenia, cardiac valve disease
What should I know, in a very general sense of the word, about epidemiology/prognosis of antiphospholipid antibody sydnrome?
- Positive antibodies don’t equal disesae
- The higher the titer, the higher the probability of clinical disease
- Once a pt has had one event, 10-30% will have another event within 4 yrs, and higher titers confer greater risks.
- Risk of stroke in pts with antibody positivity is significantly exacerbated by OCPs or smoking
- lupus anticoagulant has a higher risk of thrombosis than anti-cardiolipin, while positivity on multiple assays increases risk of thrombosis and pregnancy complications
(other less important facts: you can also see these antibodies in isolation, in SLE and RA, in a drug-induced fastion, or as part of syphilis or HIV)
What is catastrophic anti-phospholipid antibody syndrome?
widespread thrombotic disease with multi-organ failure
it develops in less than 1 wk
seen in less than 1% of pts with antiphospholipid antibody syndrome but has a mortality of 50%
What is the pathophysiology of anti-phospholipid antibody syndrome?
these antibodies may inhibit natural anticoag proteins, activate platelets, cause endothelial cell activation, up regulate tissue factor (which is a pro-coagulant in the clotting cascade), or promote antibody-mediated complement activation (this last point is esp. important- she shows evidence from research in mice)
In any case, we know that the antiphospholipid antibodies themselves directly pathogenic- they aren’t just markers of another disease process (they cause disease when we put them in mice and disease is removed when we remove the antibodies)
What do you do for primary prophylaxis in antiphospholipid antibody syndrome?
general measures to prevent thrombosis (no estrogen, no smoking, and movement when you take a long trip)
give low dose aspirin (or hydroxychloroquine/statins- not emphasized in lecture)
these are pts with antibodies but no episodes of thrombosis
What do you do for secondary prophylaxis in pts with antiphospholipid antibody syndrome?
after at least one event, give life-long anticoagulation for spontaneous and/or life-threatening events.
usually give coumadin (which is contraindicated in pregnancy)
Moderate intensity warfarin/coumadin is fine. You want INR around 2-3 (I’m not going to memorize this)
What do you do to treat pregnancy loss from antiphospholipid antibody syndrome?
Heparin and low dose aspirin during pregnancy.
In extreme cases give IVIG
If the pt has never been pregnant before but positive antiphospholipid antibodies, try observation and low dose aspirin only.
