Z Geburtshilfe Neonatol 2015; 219 - FV13_3
DOI: 10.1055/s-0035-1566532

Removal of soluble Fms-like tyrosine kinase (sFlt-1) by plasma-specific apheresis: pilot study in women with very preterm preeclampsia

W Schaarschmidt 1, H Hagmann 2, B Roth 3, T Cingoez 2, A Karumanchi 4, J Wenger 5, KJ Lucchesi 5, H Tamez 6, T Lindner 7, A Fridmann 8, U Thome 9, A Kribs 4, M Danner 3, S Hamacher 10, P Mallmann 11, H Stepan 1, T Benzing 2, R Thadhani 5
  • 1University Hospital Leipzig, Department of Obstetrics, Leipzig, Germany
  • 2University of Cologne, Renal Division and Department of Medicine and Center for Molecular Medicine, Cologne, Germany
  • 3University of Cologne, Department of Neonatology, Cologne, Germany
  • 4Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Medicine and Obstetrics and Gynecology, Boston, United States
  • 5Massachusetts General Hospital, Division of Nephrology, Boston, United States
  • 6Beth Israel Deaconess Medical Center, Harvard Medical School, Department of Cardiology, Boston, United States
  • 7University Hospital Leipzig, Department of Internal Medicine, Neurology and Dermatology, Leipzig, Germany
  • 8University of Cologne, Department of Obstetrics and Gynecology, Cologne, Germany
  • 9University Hospital Leipzig, Department of Neonatology, Leipzig, Germany
  • 10University of Cologne, Institute of Medical Statistics, Informatics and Epidemiology, Cologne, Germany
  • 11University of Cologne, Cologne Excellence Cluster on Cellular Stress Response in Aging Associated Diseases, Cologne, Germany

Background: Soluble Fms-like tyrosine kinase-1 (sFlt-1) is a potential therapeutic target in preeclampsia. We evaluated the safety and efficacy of treating women with very preterm preeclampsia using a plasma-specific dextran sulfate (PSDS) column to remove circulating sFlt-1.

Methods: This was an open study of up to three extra-corporeal PSDS-apheresis treatments in 10 women with very preterm preeclampsia to determine the extent of sFlt-1 and proteinuria reduction, and its safety for mother and fetus.

Results: Six patients with very preterm preeclampsia (mean gestational age 29 + 2 weeks) underwent one PSDS-apheresis treatment; three were treated twice, and one for three times. The apheresis volumes ranged from 400 – 1500 ml. Mean starting sFlt-1 concentration was 18,342 pg/mL (range 8,243 – 35,301 pg/mL) with a 17% mean reduction per treatment (range 6 – 28%). Mean starting protein:creatinine (P/C) ratio was 6.4 g/g (range 0.4 – 16.9 g/g); mean reduction per treatment was 39% (range 88% reduction to 30% increase). Among women treated multiple times, pregnancy continued on average for 11 days (range 7 – 19 days). The most common side effect during treatment was transient blood pressure reduction (˜10 – 20 mmHg), managed by withholding antihypertensive therapies before treatment, saline prehydration, and reducing blood flow through the apheresis column. There were no adverse effects to fetuses or neonates.

Conclusions: Therapeutic apheresis reduces circulating sFlt-1 and proteinuria in women with very preterm preeclampsia, enabling pregnancy to continue. A controlled trial is needed to determine whether apheresis to remove sFlt-1 safely prolongs pregnancy.