Placenta derived factors involved in the pathogenesis of the liver in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP): A review

Aim: With this review we try to unravel if placenta-derived factors are able to initiate liver sinusoidal endothelial cells (LSEC) decay in HELLP syndrome and eventually cause the development of sinusoidal obstruction syndrome (SOS).

Background: Haemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is a severe complication of pregnancy. It is characterized by elevated liver enzymes, low platelet count and haemolytic anaemia. The risk of developing HELLP syndrome within a pregnancy is 0.1-0.8%. The mortality rate among women with HELLP syndrome is 0-24% and the perinatal death goes up to 37%. The aetiology of HELLP syndrome is not fully understood but the pathogenesis of the liver pathology in the HELLP syndrome resembles that of a SOS with endothelial damage of the LSECs which ultimately leads to liver failure.

Objectives: We hypothesize that placenta derived factors cause LSEC damage and thereby liver dysfunction.

Methods: We searched in the PubMed database for relevant articles about placenta derived factors involved in endothelial activation especially in the liver. We yielded eventually 55 relevant articles.

Results: Based on this literature search we associate that in HELLP syndrome there is an increase of soluble fms-like tyrosine kinase (sFlt1), vascular endothelial growth factor (VEGFR), soluble endoglin (sEng), galectin-1 (Gal-1), endothelin-1 (ET-1), Angiopoietin 2 (Angs-2), Asymmetric dimethylarginine (ADMA), activin B, inhibin A, Fas ligand (FasL) and heat shock protein 70 (Hsp70).

Conclusion: We assume that these eleven increased placenta derived factors are responsible for LSEC damage which eventually leads to liver failure. This concept shows a possible design of the complicated pathophysiology in HELLP syndrome. However further research is required.