Chairs: H. Zeisler (Vienna, Austria), W. Schaarschmidt (Frankfurt, Germany)
|Cerebro-placental ratio and fetal response to maternal extracorporal sFlt-1 removal
1 Universitätsklinikum Frankfurt, Klinik für Frauenheilkunde und Geburtshilfe, Frankfurt/ Main, Germany
Abstract text :
Schaarschmidt W, Hagmann H, Roth B, Cingoez T, Karumanchi SA, Wenger J, Lucchesi KJ, Tamez H, Lindner T, Fridman A, Thome U, Kribs A, Danner M, Hamacher S, Mallmann P, Stepan H, Benzing T, Thadhani R.
Background: Preeclampsia is a devastating complication of pregnancy affecting both mother and fetus. 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 to 1500 ml. Mean starting sFlt-1 concentration was 18,342 pg/mL (range 8243–35,301 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; especially no changes in cerebro-placental ratio.
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.
|Treatment of very preterm preeclampsia via heparin mediated extracorporeal LDL-precipitation (H.E.L.P) apheresis
1 University Freiburg Medical Center, Clinical Chemistry, Freiburg, Germany
2 University Freiburg Medical Center, Department of Medicine IV (Nephrology and Primary Care), Freiburg, Germany
3 University Freiburg Medical Center, Department of Obstetrics and Gynecology, Freiburg, Germany
Abstract text :
Question: Preeclampsia (PE) is a life-threatening disease in pregnancy, but no treatment options other than sectio exist. In PE, lipid metabolism is substantially altered, and remnant removal disorder like lipoproteins have been observed in PE. Consequently, lipid apheresis is currently being explored as a possible therapeutic approach to prolong preeclamptic pregnancies. In this context, the elimination of endothelial markers sFlt-1 and PlGF is in open debate.
Methods: In the Freiburg H.E.L.P.-Apheresis Study,the prolongation of gestation by H.E.L.P.-apheresis in 6 women with very preterm PE (24 to 27 gestational weeks) is compared to a matched historic untreated PE-group. Pre- and post-apheresis levels of sFlt-1 and PlGF, were monitored. Serum lipids pre- and post-apheresis and during lipid rebound were analyzed in detail via ultracentrifugation.
Results: In the PE-group, average time from admission to birth was 15.0 days compared to 6.3 days in controls (p = 0.027), resulting in a mean fetal weight gain of 101 g (p = 0.029). All children were released in healthy conditions. SFlt-1 significantly increased initially due to heparin release, dropping to almost pre-apheresis levels after apheresis, with sFlt-1/PLGF ratio remaining unaffected. Apheresis efficiency of plasma lipids was lower than expected. Lipids returned to previous pre-apheresis levels before the next apheresis even though apheresis was repeated within 2.9 ± 1.2 days. Apparent fractional catabolic rates and synthetic rates were substantially elevated. The distribution of LDL-subclasses after apheresis shifted to a remnant disease like lipoprotein, with increased large buoyant LDL, while intermediate-density lipoprotein levels remained unaffected.
Conclusion: Addressing sFlt-1/PLGF seems not to be a suitable target for successful apheresis treatments. Lipid metabolism is highly accelerated in preeclampsia, likely outbalancing remnant removal mechanisms. Since cholesterol-rich lipoprotein remnants are able to accumulate in the vessel wall, remnant lipoproteins may contribute to the severe endothelial dysfunction observed in preeclampsia.
|Longer-term follow-up of mothers and children receiving immunoadsorption treatment during pregnancy – Vienna experience
1 Medical University of Vienna, Department of Internal Medicine III, Wien, Austria
2 Medical University of Vienna, Department of Pediatrics and Adolescent Medicine, Wien, Austria
3 Medical University of Vienna, Department of Obstetrics and Gynecology, Wien, Austria
Abstract text :
There is a paucity of data on the safety of immunoadsorption during pregnancy for mother and child. In 2002, we have reported on 5 parous women receiving immunoadsorption at our center. Here we have reanalyzed these and all subsequent immunadsorption treatments in parous women from 1994 through 2017, and have further assessed the outcomes of their children. Our aim was to use these retrospective data for future guidance of women wishing to become pregnant under medical conditions that necessitate immunoadsorption. During the period of analysis, N=26 women underwent apheresis procedures in the course of their pregnancy. N=5 of all patients were part of our regular immunoadsorption program (N=2 had hyperlipidemia, N=1 had systemic lupus erythematosus [SLE], N=1 had myasthenia gravis and N=1 had multiple sclerosis). By contrast, N=21 of all patients were acutely referred, specifically N=7 patients with maternal anti-Ro antibodies (i.e. mothers who had a previous child with anti-SSA/Ro-associated congenital heart block or very high anti-SSA/Ro titer) and N=6 patients with high SLE activity. The remaining N=8 acutely referred patients suffered from gestational pemphigoid, multiple sclerosis or hyperlipidemia. Most of the antibody-based IgG immunoadsorption treatments were performed using TheraSorbTM Ig adsorbers, while LDL immunoadsorption tretments were performed using TheraSorbTM LDL adsorbers (Miltenyi). The mothers all survived. In 3 women, who were all acutely referred patients, intrauterine fetal death occurred, while 23 children are alive today. Preliminary data indicate that birth weight in the majority of the babies was below the 10th percentile. In conclusion, long-term antibody-based immunoadsorption was beneficial and well tolerated in children from women who were already part of our regular immunoadsorption program. In acutely referred patients, where immunoadsorption was the last therapeutic option, we counted 18 surviving babies in 21 pregnancies; all 18 children are alive to date. Our experience is limited by sample size, a collective effort should therefore be made among additional immunoadsorption centers to offer further guidance to women wishing to become pregnant under severe medical conditions necessitating immunoadsorption.
|Lipoprotein Apheresis Treatment during Pregnancy
1 Royal Brompton & Harefield NHS Foundation Trust, Harefield Hospital, Cardiology, Harefield, Middlesex, United Kingdom
Abstract text :
A 32 year old British Iraqi lady was diagnosed with homozygous familial hypercholesterolaemia (HoFH) of the low density lipoprotein (LDL) receptor (C281W/C281W) at the age of 3. She commenced lipoprotein apheresis at the age of 9 in Qatar and moved to the UK in 2000 where she was recommended apheresis following at gap of 2½ years with no treatment. Initially she was treated on the Kaneka LA15 system but changed to DFPP after 16 years following an allergic reaction. In 2011 she became pregnant and was treated weekly on the DFPP system with up to 6L of plasma. She received apheresis up to the 37th week when she delivered a healthy girl. She recommenced Atorvastatin 80mg, Ezetimibe and Colestagel 2 weeks post-delivery.
In July 2015 she moved apheresis units and planned another pregnancy, hence stopping her medication in November 2015. She suffered an ectopic pregnancy in April 2016 and a miscarriage in July 2016 but then became pregnant in September 2016.
Pre-pregnancy she was treated weekly on the DFPP system with 3-4L plasma at each treatment. Weekly apheresis treatments continued until November 2016, when, due to significant increases in both total and LDL cholesterol, treatment was increased to twice weekly. Treatment volumes were decreased to between 2-3L of plasma and twice weekly treatment continued until she delivered a healthy baby girl at 38 weeks. All treatments were carried out using peripheral venous access. Cholesterol lowering medication was restarted 5 days post-delivery and lipoprotein apheresis 2-weeks afterwards. PCSK9 inhibitors were commenced in addition to the above therapy in September 2017.
The mean LDL reduction pre cessation of medication was 66.5% (mean post treatment LDL 3.16mol/L). The lipid reductions achieved during the different treatment protocols are shown in the table.
|Paediatric data from the WAA register – Up date
1 Umea University, Sweden, Public Health and Clinical Medicine, Umea, Sweden
2 WAA Registry Study Group, , New South Wales, Australia
3 WAA Registry Study Group, , Vienna, Austria
4 WAA Registry Study Group, , Roeselar, Belgium
5 WAA Registry Study Group, , Frydek-Mistek, Czech Republic
6 WAA Registry Study Group, , Hradec Kralove, Czech Republic
7 WAA Registry Study Group, , Prague, Czech Republic
8 WAA Registry Study Group, , Ostrava, Czech Republic
9 WAA Registry Study Group, , Rostock, Germany
10 WAA Registry Study Group, , Rome, Italy
11 WAA Registry Study Group, , Livorno, Italy
12 WAA Registry Study Group, , Vilnius, Lithuania
13 WAA Registry Study Group, , Amsterdam, Netherlands
14 WAA Registry Study Group, , Maastricht, Netherlands
15 WAA Registry Study Group, , Oslo, Norway
16 WAA Registry Study Group, , Skopje, Republic of Macedonia
17 WAA Registry Study Group, , Coimbra, Portugal
18 WAA Registry Study Group, , Zagreb, Croatia
19 WAA Registry Study Group, , Barcelona, Spain
20 WAA Registry Study Group, , Orebro, Sweden
21 WAA Registry Study Group, , Huddinge, Sweden
22 WAA Registry Study Group, , Linköping, Sweden
23 WAA Registry Study Group, , Lund, Sweden
24 WAA Registry Study Group, , Umea, Sweden
25 WAA Registry Study Group, , Uppsala, Sweden
26 WAA Registry Study Group, , Skövde, Sweden
27 WAA Registry Study Group, , Karlstad, Sweden
Abstract text :
The electronic registration through a web-page has been possible, at no cost, since 2002. So far 36 centres from 17 countries have entered data. A total of 87147 procedures (12853 patients) have been reported up to January 18, 2018. Data was missing of the age of the patients in 159 procedures (46 patients). A total of 598 children (4.7%) represented the age 0 up including 18 years and another 162 with the age 19 or 20 years (1.3%) these groups had performed 3519 (4.0% of all) and 1115 (1.3%) procedures, respectively. Most children were treated with stem cell collection (51%) adding collection from donors (3%), plasma exchange by centrifugation (31%) or filtration (3%), photopheresis (5%), lipid apheresis in 9 children.
The extent of work load in the units for these children was most pronounced for centrifugation (31%), photopheresis (25%), lipid apheresis (14%), and cell collection 12%). No documented child or young adult died due to apheresis. Side effects appeared during procedures in children, young adults versus adults either as mild (in 1.9, 2.3 versus 2.4%), moderate (2.3, 1.8, 3.3%) or severe (0.2, 0.2, 0.3%). The most common diagnoses treated were mainly oncological diseases (40%), haematological (24%), neurological (9%) and transplantation related reasons (8%).
The distribution of the treatments over the years will be reported.
Conclusion: Six percent of apheresis activities are performed on children and young adults. Most children perform apheresis for stem cell collection. However, these procedures are not so numerous.