599: Pregnancy-associated atypical hemolytic uremic syndrome: some answers

Abstract

Pregnancy-associated atypical hemolytic uremic syndrome (p-aHUS) is a rare and life-threatening disorder, which may be mistaken for hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. We sought to identify laboratory features that differentiate p-aHUS from HELLP. PubMed was searched (inception to Sep ‘17) with MeSH terms “pregnancy” AND “hemolytic-uremic syndrome”, to identify cases of atypical hemolytic uremic syndrome in pregnancy or postpartum. 395 articles were screened, with p-aHUS cases excluded if diagnosis was made <20 weeks gestation (n=3), >2 weeks postpartum (n=2) or following miscarriage (n=3). HELLP cases (>20 weeks gestation) were identified from our institutional database (Jan ‘13 – Dec ‘17). For recurrent p-aHUS (n=2) or HELLP (n=4), the index pregnancy was selected. Laboratory data were abstracted as peak values [aspartate transaminase (AST, U/L); creatinine (mg/dl); lactate dehydrogenase (LDH, U/L)] or nadir values [hemoglobin (g/dl); platelet count (k/μl)] during hospital course. Data were presented as median (interquartile range), with analysis by test of medians, α=0.05. Receiver operating characteristic (ROC) curves were used to assess individual lab parameters for diagnosis of p-aHUS. We identified 29 unique cases of p-aHUS and 44 unique cases of HELLP syndrome. Women with p-aHUS were more often younger (27.8±6.6 vs. 35.6±3.5 years, p<0.001) and nulliparous (89% vs. 46%, p=0.001), but gestational age at delivery was no different (35.4±3.5 vs. 35.9±4.3 weeks, p=0.64). Hemoglobin and platelet count were lower, and LDH and creatinine levels markedly higher, in p-aHUS vs. HELLP (Table 1). AST levels did not differ between groups. Levels of creatinine and LDH were most useful for diagnosis of p-aHUS, with area under the ROC curve 0.98 (0.95-1.0) and 0.94 (0.89-0.99), respectively (Figure 1). The optimal cut-points to diagnose p-aHUS (vs. HELLP) was creatinine ≥1.9 mg/dl (+ likelihood ratio 21.2) and LDH ≥1850 U/L (+ likelihood ratio 27.4). The combination of creatinine ≥1.9 mg/dl and LDH ≥1000 U/L was seen in 91% of p-aHUS cases and 0% of HELLP cases (p<0.001). We find that standard laboratory data differentiate p-aHUS and HELLP syndrome. Creatinine and LDH levels are most discriminatory, and when both are markedly elevated the diagnosis of p-aHUS is likely.View Large Image Figure ViewerDownload Hi-res image Download (PPT)