Treatment of very preterm preeclampsia via heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) apheresis: The Freiburg preeclampsia H.E.L.P.-Apheresis study

Pregnancy Hypertens. 2018 Apr:12:136-143. doi: 10.1016/j.preghy.2018.04.007. Epub 2018 Apr 11.

Abstract

Objective: Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as cure to allow prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1.

Study design: Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30-41 years) with very preterm PE (24+4 to 27+0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission (<28 GW; n = 6). Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1 and PlGF were monitored.

Main outcome measures: In apheresis patients (2-6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels throughout treatments, with sFlt-1/PLGF ratio remaining unaffected.

Conclusions: H.E.L.P.-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

Keywords: Apheresis; Fetal outcome; Preeclampsia; Prolongation of pregnancy; sFlt-1.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Biomarkers / blood
  • Blood Component Removal / adverse effects
  • Blood Component Removal / methods*
  • Case-Control Studies
  • Cholesterol, LDL / blood*
  • Female
  • Germany
  • Gestational Age
  • Heparin / administration & dosage*
  • Heparin / adverse effects
  • Humans
  • Pilot Projects
  • Placenta Growth Factor / blood
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / physiopathology
  • Pre-Eclampsia / therapy*
  • Pregnancy
  • Premature Birth / etiology
  • Premature Birth / prevention & control*
  • Time Factors
  • Treatment Outcome
  • Triglycerides / blood
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Young Adult

Substances

  • Anticoagulants
  • Biomarkers
  • Cholesterol, LDL
  • PGF protein, human
  • Triglycerides
  • Placenta Growth Factor
  • Heparin
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1