Early Pregnancy-Associated Atypical Hemolytic Uremic Syndrome (aHUS)

Introduction: aHUS in pregnancy is typically reported to occur in the third trimester. Here we report a case of aHUS presenting in the first trimester of pregnancy. Case Description: A 30 year old G2P0A1 diabetic biracial woman presented at 9 weeks gestation with new hypertension. By 18 weeks, she developed acute kidney injury and macular edema. Investigations revealed hemoglobin 68 g/L, platelets 120 x 109/L, LDH 588 U/L, undetectable haptoglobin and schistocytes. Creatinine increased from 50 to 88 umol/L, and microscopic hematuria and proteinuria >1 g/day were detected. ASA 162 mg, low molecular weight heparin, and anti-hypertensives were prescribed. Pre-eclampsia (PET) was ruled out as her symptoms began within the first trimester, and normal uterine artery doppler results were obtained. Placental growth factor levels at 24 and 28 weeks were >100 pg/mL. HELLP syndrome was excluded given the timing in pregnancy (<20 weeks) and normal liver transaminases. TTP was excluded by normal ADAMTS13. Complement Factor H autoantibody was negative. Complement studies revealed elevated plasma C5b-9 level of 1.05 (normal <0.3 mg/L). aHUS was diagnosed and eculizumab (ECU) was prescribed. Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells (Noris, Blood, 2014) was abnormal pre-treatment with ECU (activated 223%, normal <150%), and normalized with ECU therapy (activated 123%, normal <150%). Genetic testing revealed a Complement Factor I mutation, NM_000204.3:c.550G/A, p. Vall84Met reported as pathogenic, confirming primary aHUS. Due to worsening renal function, she delivered a healthy baby at 30 weeks gestation by Caesarean section. A renal biopsy performed 3 weeks postpartum demonstrated features of TMA, mainly chronic (i.e. treated) and advanced diabetic nephropathy. Six months postpartum, she required dialysis. aHUS is in clincial remission on ECU, and she awaits kidney transplantation. Discussion: aHUS is classically described to occur late in pregnancy or postpartum. Here, this patient presented uniquely during the first trimester with complement function testing aiding the diagnosis. Thus, TMA in pregnancy is not always PET or HELLP and aHUS should be considered as the diagnosis particularly for presentations occurring prior to 20 weeks gestation. Episodes of severe PET/ HELLP should trigger TMA workup for underlying complement disorder.

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