HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of preeclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome (aHUS), a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we utilized a functional complement assay, the modified Ham test, to test sera of women with classic or atypical HELLP syndrome, preeclampsia with severe features, normal pregnancies and healthy non-pregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was found in participants with classic or atypical HELLP compared to normal pregnancy and non-pregnant controls. Mixing HELLP serum with eculizumab containing serum resulted in a significant decrease in cell killing compared to HELLP serum alone. In conclusion, HELLP syndrome is associated with increased complement activation demonstrated by the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and confirm its pathophysiology relates to aHUS.

National Heart Lung and Blood Institute grants T32HL007525 and R01HL133113.

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