BASIC SCIENCE: OBSTETRICS Soluble endoglin in preeclamptic patients with or without HELLP syndrome Alexandre Hertig, MD, PhD; Julie Fort; Guillaume Lefevre, MD; Nathalie Chabbert-Buffet, MD, PhD; Martine Uzan, MD; Eric Rondeau, MD, PhD; Patrick Rozenberg, MD OBJECTIVE: The pathogenesis of the HELLP (hemolysis, enzyme liver, low platelets) syndrome is unknown. Recently soluble endoglin (sEng) was identified as a cause of the appearance of schistocytes and liver pathology in an animal model of preeclampsia (PE). STUDY DESIGN: We explored the value of sEng in 82 women who de- livered in a context of normal pregnancy (NP, n = 10), PE (n = 49), or HELLP (n = 23). RESULTS: sEng was elevated in pathological pregnancies (66.7  62 and 75.7  48 pg/mL in PE and HELLP, respectively, vs 5.29  1.25 in NP, P  .001 for both comparisons) and was correlated with an in- crease in transaminases (r 2 = 0.17; P = .05), but it was not statisti- cally different between PE and HELLP. CONCLUSION: Although recent literature findings demonstrated a role of sEng in the pathophysiology of HELLP syndrome in animal models, we found that, at the time of delivery, sEng was not specifically elevated in preeclamptic patients with HELLP. Key words: endoglin, HELLP (hemolysis, enzyme liver, low platelets) syndrome, preeclampsia, soluble form of the vascular endothelial growth factor type 1 receptor Cite this article as: Hertig A, Fort J, Lefevre G, et al. Soluble endoglin in preeclamptic patients with or without HELLP syndrome. Am J Obstet Gynecol 2010;202:594.e1-4. P athophysiology of the maternal syn- drome of preeclampsia is not en- tirely understood. However, Maynard et al 1 in 2003 published a seminal paper demonstrating the role of the soluble form of the vascular endothelial growth factor type 1 receptor (sFlt-1) in preg- nancy-induced hypertension and albu- minuria. As a result, the following schema has become widely accepted: be- cause of poor pseudovasculogenesis, 2 a placenta will produce excessive quanti- ties of numerous soluble mediators. The concentrations of these mediators progressively increase in maternal serum from the end of the first trimester through the end of pregnancy, altering endothelial function, thus leading to sys- temic hypertension, glomerular endo- theliosis, and liver and brain disor- ders. 3-7 Although sFlt-1 is important, other antiangiogenic factors are proba- bly at work here. Recently the soluble form of endoglin (sEng), a receptor for transforming growth factor beta on endothelial cells, has been incriminated on the basis of ex- perimental findings in the pathophysiol- ogy of a severe variant of preeclampsia, the hemolysis, enzyme liver, low platelets (HELLP) syndrome. 8 Briefly, it was shown in this paper that: (1) coinfection of gravid rats with 2 recombinant viruses encoding sEng and sFlt-1 could repro- duce elements of the human HELLP syn- drome in animals; and (2) sEng levels were significantly higher in blood from women delivering a baby in a context of the HELLP syndrome than in pre- eclampsia, even in its severe forms. 8 Later it was also reported in a large pop- ulation that sEng was indeed increased in maternal blood from women with pre- eclampsia, relative to women with normal outcome, from the 20th week of gestation; 4 however, this paper did not address the specific importance of sEng in respect of HELLP syndrome. Regardless, the relative concentration of several factors could, in conjunction with individual susceptibili- ties (ie, maternal endothelial thresholds), arouse different clinical syndromes. As far as HELLP syndrome is concerned, an excessive concentration of sEng and sFlt-1 is thought to play a causal role. Be- cause this has not yet been confirmed, nei- ther prospectively nor retrospectively, we explored the value of sEng in women with pathological pregnancies and tried to es- tablish correlations with clinical and bio- logical data. Our hypothesis was that sEng would be significantly higher in patients with HELLP syndrome vs patients with the classical form of preeclampsia. MATERIALS AND METHODS Population study The aim of this retrospective study was to determine whether the maternal serum From the Institut National de la Santé et de la Recherche Médicale (Drs Hertig and Rondeau), Service de Biochimie et Hormonologie (Dr Lefevre), Service de Gynécologie-Obstétrique (Dr Chabbert-Buffet), and Urgences Néphrologiques et Transplantation Rénale, Assistance Publique–Hôpitaux de Paris, Hôpital Tenon (Dr Rondeau), Hôpital Tenon, and Université Pierre et Marie Curie (Drs Hertig and Rondeau), Paris, and Service de Gynécologie- Obstétrique, Hôpital de Poissy (Ms Fort and Dr Rozenberg), and Service de Néphrologie, Centre Hospitalier Intercommunal Poissy-Saint Germain (Dr Uzan), Poissy, France. Received Oct. 9, 2009; revised Dec. 24, 2009; accepted March 3, 2010. Reprints: Alexandre Hertig, MD, PhD, Institut National de la Santé et de la Recherche Médicale Unité 702, Hôpital Tenon, 4 Rue de la Chine, 75020 Paris, France. alexandre.hertig@tnn.aphp.fr. 0002-9378/$36.00 • © 2010 Mosby, Inc. All rights reserved. • doi: 10.1016/j.ajog.2010.03.006 Research www. AJOG.org 594.e1 American Journal of Obstetrics & Gynecology JUNE 2010