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

R Thadhani, T Kisner, H Hagmann, V Bossung… - Circulation, 2011 - Am Heart Assoc
R Thadhani, T Kisner, H Hagmann, V Bossung, S Noack, W Schaarschmidt, A Jank, A Kribs…
Circulation, 2011Am Heart Assoc
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 …
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.
Am Heart Assoc