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HELLP! I Need Somebody (Preferably a Rheumatologist)… Distinguishing TMA Syndromes in Pregnancy

February 19 2016 2:07 AM ET via RheumReports RheumReports

Obstetrical complications in patients with pre-existing rheumatological diagnoses can be challenging. If that pre-existing diagnosis is systemic lupus erythematosus (SLE) or antiphospholipid antibody syndrome (APS), the level of complication (and physician stress!) can increase exponentially.

Dr. Laskin delivered an excellent talk on the differential diagnosis of catastrophic antiphospholipid antibody syndrome (CAPS) in an obstetrical setting entitled "Antiphospholipid Antibody Syndrome: A Long and Winding Road."

When a pregnant woman presents with hypertension, elevated liver enzymes, and low platelets, the differential diagnosis most certainly includes pre-eclampsia and HELLP (hemolytic anemia, elevation in liver enzymes, and low platelets) syndrome. However, in patients with a prior diagnosis of APS or SLE, the differential diagnosis may be broadened to include the possibility of active APS, CAPS, or SLE flare. In addition, low platelets in a pregnant or immediately post-partum woman may be seen with other syndromes that are included under the umbrella term of thrombotic microangiopathy (TMA) syndromes. 

TMA syndromes present with a constellation of findings including hemolytic anemia, thrombocytopenia, and organ injury. These syndromes include thrombotic thrombocytopenia purpura (TTP); atypical hemolytic uremic syndrome (HUS); HELLP; and CAPS. Each of the prior subtypes has its own associated clinical symptoms as well as laboratory findings. However, in certain cases, distinguishing between these different diagnoses may be unclear.

Regarding APS, there are different subtypes of antiphospholipid (aPL) antibodies. Of these subtypes, lupus anticoagulant (LAC) is most clinically significant and anti-cardiolipin antibodies (IgG>IgM) are more significant than anti-beta-2-glycoprotein antibodies. 

CAPS is characterized by: 

  1. involvement of 3 or more organ systems

  2. all system manifestations must occur in a period of <1 week

  3. there is histopathologic evidence of small vessel occlusion

  4. there is lab confirmation of the presence of aPL

Definite CAPS is defined by the presence of all four above criteria. In individuals with a background of SLE, CAPS always carries a worse prognosis.

APS and CAPS have different clinical presentations. APS targets medium and large vessels leading to vessel occlusion, results in single peripheral venous or arterial thromboses, is not associated with DIC, is not associated with HELLP syndrome, and has a mortality of 5% at 5 years. Conversely, CAPS involves small vessels, may affect unusual organs( e.g. ovaries, uterus, bone marrow, testes), is associated with DIC in 20% of cases, is frequently associated with HELLP syndrome in the puerperium, and carries a mortality rate that has varied in the literature between 36.5-55%.

In a pregnant woman with a pre-existing rheumatological diagnosis such as APS or SLE, distinguishing between a SLE flare, HELLP, or CAPS can be challenging. Regarding the difference between SLE flare and HELLP, with HELLP one would expect to see hypertension, increased reflexes, proteinuria, increased uric acid levels, increased liver enzymes, as well as increased complement. With a SLE flare, one would expect decreased complement, increased anti-dsDNA, proteinuria with active urinary sediment, and other symptoms of a SLE flare.

The distinction between CAPS and HELLP can be a bit more obscure, depending on the clinical presentation. CAPS often follows HELLP in pregnancy related cases. HELLP itself can actually worsen, or wax and wane even after delivery of the baby; however, it often does not have a protracted course. Overall, CAPS should be suspected in a patient with microangiopathic hemolytic anemia (MAHA) with multi-organ involvement, with a history of APL or a high titre of aPL. Indicators of poor prognosis include age > 36 years, pulmonary and renal involvement, and ANA positivity. The primary causes of death are cerebral and cardiac involvement as well as infection.

Recognizing CAPS in the peripartum period is important because one must treat aggressively with triple or quadruple therapy. The aim of therapy is to target thrombosis and suppress the cytokine cascade involved in CAPS; however, no randomized controlled trials or meta-analyses exist for this condition in the peripartum period. Triple therapy includes glucocorticoids, IVIG plus or minus plasmapheresis (PLEX), as well as anticoagulation, and quadruple therapy includes cyclophosphamide. Other therapies that have been utilized include hydroxychloroquine, azathioprine, mycophenolate mofetil, rituximab, abatacept, sirolimus, and eculizumab. Triple and quadruple therapy have been associated with the lowest acute mortality rates.


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About the Author

Dr. Pari Basharat
Dr. Pari Basharat

Dr. Pari Basharat, BSc, MD is a Rheumatologist based in London, ON.

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