Seraph 100—A new extracorporeal device to decrease elevated sFlt‐1 in preeclamptic plasma?

There is still an unmet medical need to treat preeclampsia, a life-threatening multisystem disease affecting 4%–8% of pregnant women after 20 weeks of gestation. The main underlying pathophysiology of this generalized endothelial dysfunction with thrombotic microangiopathy, is an imbalance of circulating proangiogenic and antiangiogenic factors. These are mainly antiangiogenic markers, mediated primarily by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) as well as placental growth factor (PlGF).1 Increased levels of sFlt-1 and reduced levels of PlGF predict the subsequent development of preeclampsia.2 A sFlt-1:PlGF ratio of <38 is therefore used in clinical practice to exclude preeclampsia in women in which it is clinically suspected.3 Several extracorporeal treatments have been used to correct the sFlt-1/PlGF disbalance. Therapeutic plasma exchange (TPE) is the most widely used and easily available apheresis used in preeclampsia. Pregnancy was prolonged for about 5 days as compared to the matched group not receiving TPE. The mean decrease of the elevated sFlt-1 after one TPE is 7.96% the median decrease is 24.78%, indicating large variability.4 A more specific approach is one that is based on the positive charge of sFlt-1, which can be retained by the negatively charged dextran in full blood adsorbers that are usually used for lipoprotein apheresis. In six patients who received one treatment, the median (min–max) sFlt-1 reduction was 20.5 (7.0–26.0) %.5 However, dextrane6 and LDL-apheresis7 have more side effects than TPE. We hypothesized that the Seraph 100, a biomimetic pathogen adsorber that consists of small polyethylene beads to which heparin is covalently bound8 will remove sFlt-1, which has a heparin-binding domain. For the in vitro testing of the Seraph 100, we used a Fresenius Multifiltrate in hemoperfusion mode and plasma from a preeclamptic that we had treated with TPE. Pump speed was set to 200 mL/min. The plasma was filled in a beaker that served as sham patient. The adsorber clearance (CL) of sFLT-1 and PlGF was calculated based on the plasma perfusion rate and extraction ratio (Cpre − Cpost)/Cpre, using the equation CLdrug = Qe * (Cpre − Cpost)/Cpre, where Qe is the effective plasma flow through the adsorber and Cpre and Cpost are pre- and post-adsorber concentrations, respectively. Data are shown in Figure 1. The median (min–max) plasma clearance of the Seraph 100 for sFLT-1 based on seven pre- and post-Seraph 100 plasma levels at a pump speed of 200 mL/min was 8.9 (0.4–13.5) mL/min. Interestingly, the clearance decreased during the treatment, showing the highest clearance at the beginning of the treatment and the lowest at the end of the treatment, which could be a sign of saturation. Based on the plasma concentration before and after the start of the treatment, 3.46 × 10−6 g sFLT-1 had been removed. Further studies are needed to clarify whether the Seraph 100 decreases sFLT-1 to a clinically relevant degree and might be treatment option for patients who cannot receive blood products for religious reasons. The analysis was performed using institutional resources. Jan T. Kielstein received honoraria from ExThera Medical, the manufacturer of the Seraph 100. The remaining authors declare no conflicts of interest. All laboratory data are available upon request.