Case Presentation: Young female with history of juvenile rheumatoid arthritis, not on any medications, <2 weeks post-partum presented to us for the evaluation of thrombotic microangiopathy (TMA). Pregnancy was complicated by pre-eclampsia and gestational diabetes which had both improved after the birth of a heathy baby at term via an uncomplicated C-section. Patient had presented for her usual post-natal care visit where she complained of being uncharacteristically dizzy. She was referred to the ER where labs showed hemoglobin 5.8 g/dL (range 11.5-16), platelets 32 x 10^3/uL (140-440 x 10^3), creatinine 3.5 mg/dL (0.6-1.1), total bilirubin 4.0 mg/dL (0.3-1.2), direct bilirubin 1.5 mg/dL (0-0.5), AST 75 U/L (5-34), ALT 35 U/L (normal =55), haptoglobin <8 mg/dL (35-250 mg/dL), aPTT 26 sec (23-35), fibrinogen 350 mg/dL (163-419), PT 10.9 sec (9-10), INR 1.0, LDH 2030 U/L (125-243), Coombs negative, retic count 3.7% (0.5-1.5%). Peripheral smear was positive for schistocytes. Vitals: BP 161/88, HR 90, RR 16, O2 sats 99% on room air, afebrile. 10 days before presentation patient’s Hb was 10, plts 163, creatinine 1.0, ALT 18, AST 27, LDH 324. Patient was given 125 mg IV methylprednisolone and transferred to us. She did not have any neurological signs and symptoms; no abnormal bleeding was noticed on exam. She reported a few soft stools prior to presentation. A stool Shiga toxin PCR was done and was negative. Empiric diagnosis of atypical hemolytic uremic syndrome (aHUS) was made, and a hemodialysis catheter was placed immediately on arrival to the floor. Plasma exchange (PEX) was started urgently. ADAMTS 13 activity later came back at 80% (cut off for diagnosis of thrombotic thrombocytopenic purpura is < 10%). Patient received PEX and IV steroids for two consecutive days without any significant improvement in platelets, LDH, bilirubin, or haptoglobin. Therapy was switched to eculizumab after ADAMTS13 activity resulted, and patient was discharged home with close follow up with oncology and nephrology. Patient’s labs improved on outpatient recheck and her platelets and renal function returned to baseline within one week of initiation of eculizumab. Complement levels were later reported as normal.
Discussion: Pregnancy associated aHUS (P-aHUS) is a rare but life-threatening form of complement mediated TMA, with an incidence of 1 in 25,000 pregnancies (1). Despite its rarity, it accounts of 20% of all the aHUS cases in women. Majority of the cases are seen in post-partum period (2), and most of the patients end up under the care of Medicine. TTP/HUS carry a significant number of similarities to other pregnancy associated TMAs including pre-eclampsia and HELPP syndrome. It is also incredibly challenging to differentiate between TTP and aHUS themselves at the onset of lab abnormalities, as the diagnostic test (ADAMTS13 activity) takes a few days to result. aHUS carries a mortality rate of 25% in the acute phase and of those who survive, 50-60% end up with irreversible renal/neurological damage. Given the significant mortality rate, treatment is started empirically with high dose steroids and PEX. Initiation of eculizumab has been associated with improved renal outcomes and should be initiated as early as possible.
Conclusions: Internists should be cognizant of this rare life-threatening disorder, especially in patients in who are in their post-partum period. Hematology team should be consulted urgently for evaluation and patient should be transferred to a tertiary care center for initiation of PEX and eculizumab, and specialized care.