The H.E.L.P Aphersis as a possible intervention before 28th week of pregnancy

Transcription

1 The H.E.L.P Aphersis as a possible intervention before 28th week of pregnancy C. Contini 1 ; B. König 1 ; B. Krumrey 1, F. Markfeld-Erol 2 ; M. Kunze 2 ; S. Zschiedrich 3 ; H. Prömpeler 2 ; G. Pütz 1 ; K. Winkler 1 1 Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsklinik Freiburg 2 Abteilung für Frauenheilkunde, Geburtshilfe und Perinatologie, Universitätsklinik Freiburg 3 Klinik für Innere Medizin IV, Universitätsklinik Freiburg

2 Preeclampsia Severe pregnancy disorder 2-8% worldwide Characterized by high blood pressure and proteinuria Leading cause of maternal death (29000 in 2013) No treatment so far, only relief by cesarian section High risk for fetus in early onset PE Group of hypertensive disorders in pregnancy Often but not always IUGR (intra uterine growth restriction) Placenta malfunction, but detailed mechanisms unclear Mai 2015

3 First study of H.E.L.P.-apheresis in preeclampsia: Mothers: Improvement of blood pressure, proteinuria and edema 8/9 3 patients ( week) single treatment prolongation 3-19 Tage 6 patients ( week) multiple treatments (2-7) prolongation 5-49 Tage Newborns: 8 newborns discharged in good condition 1 newborn late-onset Sepsis Transfusion and Apheresis Science 35 (2006)

4 Triglycerides H.E.L.P.-Apheresis Heparin-mediated Extracorporal LDL Precipitation therapeutic intervention for sereve dyslipidemia ApoB containing lipoproteins + - VLDL IDL LDL1 LDL 2 LDL 6: (Very-Low-Density) (Intermediate-Density) (Low Density) Subfractions of LDL With kind permission of B.Braun Avitum GmbH

5 Manifold effects of H.E.L.P.-apheresis Lipid: ApoB: - 60 % Cholesterol: - 50 % Triglycerids: - 53 % Thrombotic markers [%] Pro-inflammatory markers IL-6-34% TNF- -25% [%] Rheology Improvement of microcirculation: acute hearing loss macular degeneration diabetic foot preeclampsia etc... [%] Cytokine 56, 2011,

6 Lipidmetabolism and preeclampsia Highest triglycerid level associated with 4-fold increase for PE* predominance of triglyceride-rich lipoproteins** Correlation of triglycerid content in IDL with diastolic blood pressure** **p<0,01 ***p<0,001 Control (n=23) 34. ± 2 week preeclampsia (n=15) 33. ± 4 week * BJOG 2006, 113: , **J Clin Endocrinol Metab 2003, 88(3): ;

7 H.E.L.P.-apheresis in early pregnancies in the University Hospital Freiburg Patients 7 pregnancies complicated by preeclampsia (ongoing) week 24+4 bis 27+0 in part IUGR and/or HELLP-Syndrome Parameter: duration of pregnancy clinical signs fetal outcome (e.g. birth weight, APGAR, RDS, ) maternal parameters (e.g. lipids, coagulation, hematology...) Mit freundlicher Genehmigung der Patientin des UKF

8 Duration of pregnancy: From first apheresis to delivery treatments ,5 7 days

9 Clinical benefit of apheresis Prolongation of gestation (Wang et al, Tadhani et al, Winkler et al No clear cut primary outcome parameter Apheresis may help, but why? sflt (Tadhani) but H.E.L.P sflt??? TG rich lipoproteins microcirculation

10 Lipoproteinprofile: Baseline before first apheresis healthy pregnancies (week 23-28) Controls from: J Clin Endocrinol Metab 2003, 88(3):

11 Lipoproteinprofile: Baseline before first apheresis healthy pregnancies (week 23-28) Controls from: J Clin Endocrinol Metab 2003, 88(3):

12 Comparison before after apheresis before apheresis after apheresis expected after apheresis

13 Recovery of ApoB-Lipoproteins Recovery to basal level: 8-10 days Normal pregnancy??? Rau, Dissertation, Freiburg, 1995

14 Lipids in cord blood of newborns MW ± SD uncomplicated pregnancy week n=27* PE week n=12 * * *Pecks, Z Geburtsh Neonatol (2012)

15 Lipids in cord blood of newborns MW ± SD uncomplicated pregnancy week n=27* PE week n=12 * * n=3 * *Pecks, Z Geburtsh Neonatol (2012)

16 Clinical benefit of apheresis Prolongation of gestation (Wang et al, Tadhani et al, Winkler et al Apheresis may help, but why? sflt (Tadhani) but H.E.L.P sflt??? Lipidmetabolism? microcirculation

17 PE as a result of a fetal lipidmetabolism disorder? Fetal High need on fatty acids (brain development) Maternal Lipidstorage (FA) Triglycerids placentar microcirculation VLDL LDL1 (TG-rich) Turnover Triglycerid? Quality (composition) Malabsorption Dyfunction of FAmetabolism High TG-Load: Erythrocyte function Thrombocyt function Endothelial function

18 The study team of the University Hospital Freiburg Institute of Clinical Chemistry and Laboratory Medicine C. Contini B. König B. Krumrey G. Pütz K. Winkler Department of Obstetrics and Perinatology F. Markfeld-Erol M. Kunze H. Prömpeler Clinic of Internal Medicine IV S. Zschiedrich G. Walz Thank you for your attention! B.Braun Melsungen AG provided the H.E.L.P. Plasmat Futura for the apheresis. The principal investigator K. Winkler has in the past received remunerations for talks, research participation and clinical studies by B.Braun Melsungen AG.