title: Seeking the mechanism(s) of action for corticosteroids in HELLP syndrome: SMASH study.
abstract: BACKGROUND
  Administration of dexamethasone to the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome patients (10 mg intravenously [IV] every 12 hours) shortens the disease course and reduces maternal morbidity in patients treated at the University of Mississippi Medical Center (UMMC), associated with this severe form of preeclampsia. However, the pathophysiological mechanisms involved with this intervention remain unclear.
  
  
  OBJECTIVE
  We sought to investigate the potential role of IV dexamethasone to restore the imbalance among antiangiogenic and inflammatory factors known to be significantly elevated in women with HELLP syndrome.
  
  
  METHODS
  This was a single-center prospective study of women diagnosed with HELLP syndrome who were treated for IV dexamethasone at UMMC. Blood was drawn prior to dexamethasone administration and again 12 and 24 hours after the initial dexamethasone administration. Enzyme-linked immune assays were used to measure circulating inflammatory cytokines and antiangiogenic factors. A repeated-measures analysis of variance was used to analyze the data collected before, after, and during dexamethasone administration.
  
  
  RESULTS
  Seventeen women with HELLP syndrome were enrolled in this study. Dexamethasone significantly decreased evidence of hemolysis (P = .002) and liver enzymes (P = .003), and significantly increased platelets (P = .0001) within 24 hours of administration. Circulating interleukin-6 levels after 24 hours were decreased (P < .001); soluble fms-like tyrosine kinase-1 and soluble endoglin were also significantly decreased by 24 hours after dexamethasone administration (P < .002 and P < .004, respectively). There were no significant differences in circulating levels of placental growth factor (P = .886) due to dexamethasone administration. Angiotensin II receptor autoantibody levels were unchanged by dexamethasone administration.
  
  
  CONCLUSIONS
  We conclude that 1 important mechanism of dexamethasone administration is to blunt the release of both antiangiogenic and inflammatory factors suggested to play role in the pathophysiology of HELLP syndrome.
authors: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA.
authors: Kedra
authors: K
authors: Wallace
authors: James N
authors: JN
authors: Martin
authors: Kiran
authors: K
authors: Tam Tam
authors: Gerd
authors: G
authors: Wallukat
authors: Ralf
authors: R
authors: Dechend
authors: Babbette
authors: B
authors: Lamarca
authors: Michelle Y
authors: MY
authors: Owens
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D020533:Angiogenesis Inhibitors / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D017359:HELLP Syndrome / Q000097:blood / Q000188:drug therapy*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D011446:Prospective Studies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D005938:Glucocorticoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone