Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase 1 in preeclampsia

Circulation. 2011 Aug 23;124(8):940-50. doi: 10.1161/CIRCULATIONAHA.111.034793. Epub 2011 Aug 1.

Abstract

Background: Targeted therapies to stabilize the clinical manifestations and prolong pregnancy in preeclampsia do not exist. Soluble fms-like tyrosine kinase 1 (sFlt-1), an alternatively spliced variant of the vascular endothelial growth factor receptor 1, induces a preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia. Removing sFlt-1 may benefit women with very preterm (<32 weeks) preeclampsia.

Methods and results: We first show that negatively charged dextran sulfate cellulose columns adsorb sFlt-1 in vitro. In 5 women with very preterm preeclampsia and elevated circulating sFlt-1 levels, we next demonstrate that a single dextran sulfate cellulose apheresis treatment reduces circulating sFlt-1 levels in a dose-dependent fashion. Finally, we performed multiple apheresis treatments in 3 additional women with very preterm (gestational age at admission 28, 30, and 27+4 weeks) preeclampsia and elevated circulating sFlt-1 levels. Dextran sulfate apheresis lowered circulating sFlt-1, reduced proteinuria, and stabilized blood pressure without apparent adverse events to mother and fetus. Pregnancy lasted for 15 and 19 days in women treated twice and 23 days in a woman treated 4 times. In each, there was evidence of fetal growth.

Conclusions: This pilot study supports the hypothesis that extracorporeal apheresis can lower circulating sFlt-1 in very preterm preeclampsia. Further studies are warranted to determine whether this intervention safely and effectively prolongs pregnancy and improves maternal and fetal outcomes in this setting.

Publication types

  • Case Reports
  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Component Removal / methods*
  • Cellulose / chemistry
  • Dextran Sulfate / chemistry
  • Female
  • Humans
  • Pilot Projects
  • Pre-Eclampsia / blood*
  • Pre-Eclampsia / therapy*
  • Pregnancy
  • Protein Structure, Tertiary
  • Solubility
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Vascular Endothelial Growth Factor Receptor-1 / chemistry
  • Vascular Endothelial Growth Factor Receptor-1 / isolation & purification
  • Young Adult

Substances

  • Cellulose
  • Dextran Sulfate
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1