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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 74 - Antiphospholipid Syndrome

“Living consciousness somehow is the influence that turns the possibility of something into something real...The most essential ingredient in creating our universe is the consciousness that observes it. ” - Lynne McTaggart


2018 Sonoma Zinfandel from Seghesio Family Vineyards

PB#132 - Published December 2012 (Reaffirmed 2017)


Five Pearls

  1. The clinical diagnosis of APS is made through a careful clinical history that takes into account thrombotic events, history of pregnancy loss, and development of preterm preeclampsia.

  2. Lab studies to detect specific antibodies can confirm your diagnosis, but these lab studies are not indicated when clinical criteria are not met.

  3. The three relevant antibodies on your board exam are: lupus anticoagulant, anti-β₂-glycoprotein, and anticardiolipin

  4. The worst consequence of APS is thrombosis.

  5. In pregnancy, thrombotic risk is EVEN higher. APS patients with history of thrombosis should be treated with prophylactic heparin throughout pregnancy until 6 weeks postpartum.


Antiphospholipid syndrome (APS) is such a brat

- here what happens: specific plasma antibodies (Ig) cause thromboses and other bad things (like recurrent pregnancy loss)

- the primary relevant Ig is anti-β₂-glycoprotein, which actually serves a physiological role in regulating coagulation and fibrinolysis

- lupus anticoagulant and anticardiolipin are the other two relevant antibodies

- diagnosis: 1 of these Ig must be present on two occasions at least 12 weeks apart

- associated with arterial thrombosis and VTE, autoimmune thrombocytopenia, fetal loss, preeclampsia, fetal growth restriction (FGR), placental insufficiency, and preterm delivery (PTD)


More on these specific Ig...


Lupus anticoagulant

- commonly seen in systemic lupus erythematous (SLE), but often also present in individuals without SLE (probably a misnomer)

- contrary to its name, it's often associated with thrombosis rather than anticoagulation

- with variance in sensitivity across tests for this Ig depending on reagents used by various laboratories

- it's a complicated testing process, but basically, blood is checked for clotting time. If clotting in a test tube is prolonged (I know...it's paradoxical because clinically thrombosis is seen in the body), then normal plasma is added to ensure that the prolonged clotting time is not due to clotting factor deficiencies

- a second confirmatory test includes addition or removal of phospholipid from the assay (addition of phospholipid should trigger clotting in the absence of lupus anticoagulant); if lupus anticoagulant is present, it'll bind up the phospholipid to prevent this from happening

- that was a mouthful


Anticardiolipin Ig

- diagnosed through the presence of IgG or IgM (not IgA) on enzyme-linked immunosorbent assays

- a positive result will be reported as >40 GPL (IgG) or 40 MPL (IgM)


Anti-β₂-glycoprotein Ig

- diagnosed through the presence of IgG or IgM (not IgA) on enzyme-linked immunosorbent assays

- a positive result will be reported as >99th percentile for SGU (IgG) and SMU (IgM)


Thrombosis risk in APS

- the most common (and most serious) complications are related to arterial thrombosis and VTE

- ~70% of thrombotic events are venous, particularly in places in the body other than lower extremities

- 2% of all patients diagnosed with VTE will test positive for lupus anticoagulant

- however, even among asymptomatic nonpregnant patients with APS Ig <1% will develop thromboses over a given year

- 25% risk of recurrence in patients with APS, but this risk if reduced dramatically with anticoagulation

- risk goes up significantly in pregnancy: 25% thrombotic events among APS patients occur in pregnancy; 5-10% risk of thrombosis in pregnancy or puerperium in APS patients

- arterial occlusions can happen anywhere in the body, including retina or digits

- stroke is the dreaded outcome, but very rare; most common site is middle cerebral artery

- APS Ig can be found in ~5% of otherwise healthy adults under the age of 50 who suffer stroke


Thrombocytopenia in APS

- occurs in 40-50% of patients witih APS

- difficult to distinguish from idiopathic thrombocytopenic purpura (ITP)

- treated in the same way as ITP


Other rare conditions (we'll get to common obstetrics issues in a minute...)

- AI hemolytic anemia

- livedo reticularis

- cutaneous ulcers

- chorea gravidarum

- multi-infarct dementia

- transverse myelitis

- catastrophic APS: progressive global thromboses resulting in multi-organ failure


Common obstetrics complications


Fetal and recurrent pregnancy loss

- a large proportion of early pregnancy loss due to APS is >10 wga (but these represent only a small fraction of all early SAB --> the vast majority occur <10 wga)

- 85% of women w/ APS Ig experienced at least one fetal death compared to 25% of women without APS Ig

- even though not associated with isolated, sporadic embryonic pregnancy loss, APS is associated with recurrent early pregnancy loss


Preeclampsia

- ~15% of women with preeclampsia will have APS Ig

- association is especially strong for women who develop early preeclampsia (<34 wga)

- odds ratio 5.5 for women w/ APS to develop gestational HTN

- odds ratio 8 for women w/ APS to develop severe preeclampsia


Fetal growth restriction (FGR)

- seen in 15-30% of pregnancies complicated by APS



How is APS diagnosed?

- laboratory criteria Box 1 (only check for Ig if clinical features are present, see Box 2)


Note: if preterm preeclampsia or early-onset placental insufficiency are used to make clinical diagnosis, no evidence that anticoagulation will improve future pregnancy outcomes (e.g. reduce risk of early pregnancy loss)


Management of APS in pregnancy

- antepartum surveillance is recommended in the 3rd trimester due to risk for stillbirth and FGR

- anticoagulation is important


History of thrombotic event

- prophylactically dosed heparin throughout pregnancy and continued until 6 weeks postpartum (can be switched to coumadin postpartum: who wants to stick themselves with needles?!)

- the available literature on the efficacy of this practice often includes aspirin 81 mg, as well, started no earlier than 12 wga (unclear if aspirin played a role in improving maternal/fetal outcomes)


No history of thrombotic event

- less evidence to guide decision-making in this case

- some data to support similar approach as those patients w/ thrombotic events to decrease risk of pregnancy loss

- this approach seems superior to aspirin alone

- no evidence to support or refute efficacy of IVIG (also very pricey)

- risks of corticosteroids likely outweigh benefits


One final note...

- given the increased risk of thrombosis in APS, these women should be counseled against estrogen-containing contraception over the long haul

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