Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome

Arthur J. Vaught, Eleni Gavriilaki, Nancy Hueppchen, Karin Blakemore, Xuan Yuan, Sara M. Seifert, Sarah York, Robert A. Brodsky

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant 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 observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.

Original languageEnglish (US)
Pages (from-to)390-398
Number of pages9
JournalExperimental Hematology
Issue number5
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research


Dive into the research topics of 'Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome'. Together they form a unique fingerprint.

Cite this