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THADHANI, Ravi; KISNER, Tuelay; HEMPHILL, Linda; RIGBY, Alan C; KHEDKAR, Santosh; LINDNER, Tom H; MALLMANN, Peter; STEPAN, Holger; ANANTH KARUMANCHI, S; BENZING, Thomas; HAGMANN, Henning; BOSSUNG, Verena; NOACK, Stefanie; SCHAARSCHMIDT, Wiebke; JANK, Alexander; KRIBS, Angela; COMELY, Oliver A; KREYSSIG, Claudia
Circulation, 08/2011, Letnik: 124, Številka: 8Journal Article
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. 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. 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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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