Therapeutic plasma exchange and dextran‐sulfate plasma adsorption as extracorporeal treatments of extremely preterm preeclampsia with fetal growth restriction

Abstract

Aim To evaluate effectiveness and safety of therapeutic plasma exchange (TPE) and dextran‐sulfate plasma adsorption (DSA) for extracorporeal removal of soluble Fms‐like tyrosine kinase‐1 (sFlt‐1) as part of expectant management of preeclampsia at extremely preterm gestational age. Methods Retrospective case series of six patients with preeclampsia at <28 weeks of gestation, treated with DSA or TPE. Laboratory results, clinical characteristics and neonatal outcomes were collected from charts and National Perinatal Information System. Results Fetal growth restriction (FGR) was diagnosed in all cases. Pregnancy was prolonged for a median of 14 (range 5‐74) days from admission and 10 (3‐73) days from first apheresis. A mixed effects model showed a decrease in sFlt‐1 and sFlt‐1/PlGF ratio during DSA/TPE (significant effect of time [before/after]), which was comparable between DSA and TPE (no effect of procedure type). Median absolute reduction in sFlt‐1 was 42% (inter‐quartile range [IQR] 13%‐57%) during DSA and 34% (16%‐40%) during TPE; for sFlt‐1/PlGF ratio it was 29% (22%‐36%) and 38% (29%‐42%), respectively. All procedures were well tolerated by fetuses. Anaphylactoid reaction, often with angioedema, occurred in 4/6 patients undergoing DSA and was attributed to bradykinin activation. One patient developed wound hematoma after cesarean section, possibly attributed to depletion coagulopathy. Conclusions As potential novel treatment of early preeclampsia, a non‐selective and widely available TPE was comparable to DSA regarding sFlt‐1 reduction but was associated with fewer side‐effects. Both seem to allow maternal stabilization and pregnancy prolongation even when early preeclampsia is complicated by FGR.

Prospective directions for creating a strategy for effective medicine prevention of preeclampsia (Literature review)

“…Аферез є інвазивним методом, тому проводити великі клінічні випробування буде складно. Навіть без таких випробувань цей метод, ймовірно, може знайти місце у лікуванні захворювань, що виникають у ранньому терміні вагітності, де можливості обмежені, а прогноз примарний (аналогією може бути абдомінальний серкляж, запропонований жінкам, які мали повторні передчасні пологи на дуже ранніх термінах гестації, незважаючи на те що докази, які підтверджують цю техніку, є лише з серії випадків) [24].…”

Magnetic blood purification‐based soluble fms‐like tyrosine kinase‐1 removal in comparison with dextran sulfate apheresis and therapeutic plasma exchange

“…8 In a recently published study, Gubensek et al showed that maternal stabilization can be achieved with dextran sulfate plasma adsorption (DSA) and therapeutic plasma exchange (TPE). 9 However, the researchers observed anaphylactic reactions and coagulation alterations, especially in patients treated with DSA, illustrating the need for an alternative sFlt-1 removal approach.…”

“…For example, Thadhani et al were able to reduce the blood concentrations of sFlt‐1 in five women, yielding promising results with a reduction of preeclamptic symptoms and prolonging those pregnancies by at least 14 days 8 . In a recently published study, Gubensek et al showed that maternal stabilization can be achieved with dextran sulfate plasma adsorption (DSA) and therapeutic plasma exchange (TPE) 9 . However, the researchers observed anaphylactic reactions and coagulation alterations, especially in patients treated with DSA, illustrating the need for an alternative sFlt‐1 removal approach.…”

Single-Cell Heterogeneity Restorative Chimeric Engineering Nanoparticles for Alleviating Antibody-Mediated Allograft Injury

“…In recent years, some progress has been made in the prevention and treatment of DSAs, mainly including physical adsorption and biological therapies . In vitro, the plasma exchange and immunoadsorption can reduce the serum DSA titer of patients to a certain extent; however, they are prone to supersaturation . Also, the risks of bleeding, allergy, and infection are still unavoidable, and they are still not applicable to patients with blood coagulation dysfunction. , Additionally, although the intervention strategies in vivo with gamma globulin and rituximab have achieved some efficacy, there are limitations such as low clearance efficiency, poor specificity, and bleeding. , In particular, a single-profile adsorption strategy is difficult to solve progressive and diverse subtype switching .…”

“…9 In vitro, the plasma exchange and immunoadsorption can reduce the serum DSA titer of patients to a certain extent; however, they are prone to supersaturation. 10 Also, the risks of bleeding, allergy, and infection are still unavoidable, and they are still not applicable to patients with blood coagulation dysfunction. 11,12 Additionally, although the intervention strategies in vivo with gamma globulin and rituximab have achieved some efficacy, there are limitations such as low clearance efficiency, poor specificity, and bleeding.…”