Using apheresis to remove a serum protein called soluble Fms-like tyrosine kinase-1 (Sflt-1) may help pregnant women with severe preeclampsia safely delay delivery, according to a pilot study.
‘Based on recent advances in the understanding of this condition, we and others are developing treatments for preeclampsia to allow women to safely prolong their pregnancy if they are suffering from very preterm preeclampsia,’ first author Ravi Thadhani, MD, MPH, from Massachusetts General Hospital in Boston, said in a press release.
Symptoms of preeclampsia include high blood pressure and proteinuria. The condition affects between 3% and 8% of pregnancies worldwide and can be harmful or even fatal to both the mother and newborn. Because of limited understanding about its underlying mechanisms, no cure exists other than delivery, which can be problematic if preeclampsia develops very early in pregnancy, the authors note.
In the open pilot study, Dr Thadhani and colleagues tested the safety and efficacy of removing sFlt-1 from the blood of pregnant women with very preterm preeclampsia. The serum protein sFLT-1 acts as a receptor for vascular endothelial growth factor. By inhibiting vascular endothelial growth factor activity, sFTL-1 modifies blood vessel growth. Women with preeclampsia often have elevated sFTL-1 levels.
Using apheresis, researchers removed the blood from 11 pregnant women and passed it through a negatively charged dextran sulfate column to bind and remove the positively charged sFLT-1. Participants were aged 20 to 38 years and were between 23 to 32 weeks of gestation. Inclusion criteria included systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher, new-onset protein/creatinine ratio higher than 0.30 g/g, and sFLT-1/placental growth factor ratio higher than 85.
Apheresis resulted in an 18% (range, 7% – 28%) reduction in mean sFLT-1 levels, as well as reductions of 44% in protein/creatinine ratios.
Pregnancy continued 8 days after admission (range, 2 – 11 days) in six women treated once with apheresis, and 12 days (range, 7 – 19 days) in five women treated multiple times. In comparison, delivery occurred after 3 days (range, 0 – 14 days) in untreated women with preeclampsia (n = 22) and women who delivered preterm for other reasons (n = 22); the control participants, who had been treated contemporaneously, were matched to the treated women for several factors, including gestational age at delivery.
Although antihypertensive treatments were withheld the morning of the apheresis treatment, the most common adverse effect of apheresis was transient hypotension, which was treated with saline hydration and decreasing blood flow through the column. Hypotension was not severe enough to cause any of the women to stop treatments. No significant changes in foetal heart monitoring occurred during apheresis.
Babies born to apheresis-treated women needed fewer days of supplemental oxygen than babies born to untreated women. However, neonatal test results, total days in the neonatal ICU, and days spent in the hospital did not differ between the groups.
‘Our pilot study suggested we can safely prolong pregnancy when we target removal of sFlt-1 in women with severe preterm preeclampsia, and we hope this is confirmed in randomized trials,’ Dr Thadhani. MedScape