Therapeutische Apherese als erfolgreiches Behandlungskonzept einer Alloimmunisierung in der Schwangerschaft am Beispiel von maternalen Anti-Kell- und Anti-Duffy-Antikörpern

Maternale Anti-Kell-Antikörper (Kell-AK) und Anti-Duffy-Antikörper (Duffy-AK) sind äußerst selten, können jedoch schwere fetale hämolytische Anämien verursachen. Nur etwa 3% aller positiven Antikörper-Suchtests lassen sich auf Kell-AK und Duffy-AK zurückführen. Die Behandlung hoher maternaler AK-Titer erfordert bereits in der Frühschwangerschaft ein intensives Überwachungs- und Therapieregime. Am Beispiel zweier Schwangerschaften wird gezeigt, wie die therapeutische Apherese (TA) als erfolgreiches Therapieregime bei der Alloimmunisierung mit Kell- und Duffy-AK etabliert werden konnte.

Publikationsverlauf

Artikel online veröffentlicht:
05. März 2021

• Literatur

• 1 Vaughan JI, Manning M, Warwick RM. et al. Inhibition of erythroid progenitor cells by anti-Kell antibodies in fetal alloimmune anemia. N Engl J Med 1998; 338: 798-803 doi:10.1056/NEJM199803193381204
• 2 Weiner CP, Widness JA. Decreased fetal erythropoiesis and hemolysis in Kell hemolytic anemia. Am J Obstet Gynecol 1996; 174: 547-551
• 3 Aldarweesh AF. The Duffy Blood Group System. IntechOpen [Online First], Online (Stand: 17.12.2020): https://www.intechopen.com/online-first/the-duffy-blood-group-system
• 4 Goodrick MJ, Hadley AG, Poole G. Haemolytic disease of the fetus and newborn due to anti-Fy(a) and the potential clinical value of Duffy genotyping in pregnancies at risk. Transfus Med 1997; 7: 301-304 doi:10.1046/j.1365-3148.1997.d01-38.x
• 5 Klein HG, Anstee DJ. Mollisonʼs Blood Transfusion in clinical Medicine. 12th ed. Hoboken: Wiley; 2013
• 6 Hughes LH, Rossi KQ, Krugh DW. et al. Management of pregnancies complicated by anti-Fy(a) alloimmunization. Transfusion 2007; 47: 1858-1861 doi:10.1111/j.1537-2995.2007.01408.x
• 7 Papantoniou N, Sifakis S, Antsaklis A. Therapeutic management of fetal anemia: review of standard practice and alternative treatment options. J Perinat Med 2013; 41: 71-82 doi:10.1515/jpm-2012-0093
• 8 Schettler V, De Groot K, Fassbender C. et al. Standard der Therapeutischen Apherese 2019. Deutsche Gesellschaft für Nephrologie in Zusammenarbeit mit der Gesellschaft für pädiatrische Nephrologie und dem Verband Deutsche Nierenzentren e.V.. Online (Stand: 26.06.2020): https://www.dgfn.eu/apherese-standard.html
• 9 Bio-Rad Laboratories GmbH. IH-500. Vollautomatisches System für ID-Karten. Online (Stand: 17.12.2020): https://www.bio-rad.com/en-de/product/ih-500-system?ID=NPUFID15
• 10 Schlensker KH. Hämolytische Fetalerkrankungen – pränatale Diagnostik und Therapie. In: Bolte A, Wolff F, Hrsg. Hochrisikoschwangerschaft. Heidelberg: Steinkopff; 1989: 129-148
• 11 Hansmann M, Lang N. Intrauterine Transfusion unter Ultraschallkontrolle. Klin Wochenschr 1972; 50: 930-932 doi:10.1007/BF01487926
• 12 LILEY AW. Intrauterine Transfusion of Foetus in Haemolytic Disease. Br Med J 1963; 2: 1107-1109
• 13 Schultze-Mosgau H, Poschmann A, Fischer K. et al. The scope of prenatal therapy in severe rhesus hemolytic disease. J Perinat Med 1975; 3: 44-46 doi:10.1515/jpme.1975.3.1.44
• 14 Fischer K, Poschmann A, Schultze-Mosgau H. Pränatale Diagnostik und Therapie des Morbus haemolyticus neonatorum. Monatsschr Kinderheilkd 1975; 123: 221-226
• 15 Lindenburg ITM, van Kamp IL, Oepkes D. Intrauterine blood transfusion: current indications and associated risks. Fetal Diagn Ther 2014; 36: 263-271 doi:10.1159/000362812
• 16 Tongsong T, Wanapirak C, Kunavikatikul C. et al. Fetal loss rate associated with cordocentesis at midgestation. Am J Obstet Gynecol 2001; 184: 719-723 doi:10.1067/mob.[phone]
• 17 MacGregor SN, Silver RK, Sholl JS. Enhanced sensitization after cordocentesis in a rhesus-isoimmunized pregnancy. Am J Obstet Gynecol 1991; 165: 382-383
• 18 Padmanabhan A, Connelly-Smith L, Aqui N. et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher 2019; 34: 171-354 doi:10.1002/jca.21705
• 19 Fox C, Martin W, Somerset DA. et al. Early intraperitoneal transfusion and adjuvant maternal immunoglobulin therapy in the treatment of severe red cell alloimmunization prior to fetal intravascular transfusion. Fetal Diagn Ther 2008; 23: 159-163 doi:10.1159/000111599
• 20 Ruma MS, Moise KJ, Kim E. et al. Combined plasmapheresis and intravenous immune globulin for the treatment of severe maternal red cell alloimmunization. Am J Obstet Gynecol 2007; 196: 138.e1-e6 doi:10.1016/j.ajog.2006.10.890
• 21 Isojima S, Hisano M, Suzuki T. et al. Early plasmapheresis followed by high-dose γ-globulin treatment saved a severely Rho-incompatible pregnancy. J Clin Apher 2011; 26: 216-218 doi:10.1002/jca.20288
• 22 Bellone M, Boctor FN. Therapeutic plasma exchange and intravenous immunoglobulin as primary therapy for D alloimmunization in pregnancy precludes the need for intrauterine transfusion. Transfusion 2014; 54: 2118-2121 doi:10.1111/trf.12633
• 23 Lakhwani S, Machado P, Pecos P. et al. Kell hemolytic disease of the fetus. Combination treatment with plasmapheresis and intrauterine blood transfusion. Transfus Apher Sci 2011; 45: 9-11 doi:10.1016/j.transci.2011.06.014
• 24 Dau PC. Immunologic rebound. J Clin Apher 1995; 10: 210-217
• 25 Orlin JB, Berkman EM. Partial plasma exchange using albumin replacement: removal and recovery of normal plasma constituents. Blood 1980; 56: 1055-1059
• 26 Clynes R. Immune complexes as therapy for autoimmunity. J Clin Invest 2005; 115: 25-27 doi:10.1172/JCI23994
• 27 Yu Z, Lennon VA. Mechanism of intravenous immune globulin therapy in antibody-mediated autoimmune diseases. N Engl J Med 1999; 340: 227-228 doi:10.1056/NEJM199901213400311
• 28 Palfi M, Hildén J-O, Matthiesen L. et al. A case of severe Rh (D) alloimmunization treated by intensive plasma exchange and high-dose intravenous immunoglobulin. Transfus Apher Sci 2006; 35: 131-136 doi:10.1016/j.transci.2006.07.002
• 29 Houston BL, Govia R, Abou-Setta AM. et al. Severe Rh alloimmunization and hemolytic disease of the fetus managed with plasmapheresis, intravenous immunoglobulin and intrauterine transfusion: A case report. Transfus Apher Sci 2015; 53: 399-402 doi:10.1016/j.transci.2015.07.010
• 30 Fernández-Jiménez MC, Jiménez-Marco MT, Hernández D. et al. Treatment with plasmapheresis and intravenous immunoglobulin in pregnancies complicated with anti-PP1Pk or anti-K immunization: a report of two patients. Vox Sang 2001; 80: 117-120
• 31 Fernández Alba JJ, León R, González-Macías C. et al. Treatment of D alloimmunization in pregnancy with plasmapheresis and intravenous immune globulin: case report. Transfus Apher Sci 2014; 51: 70-72 doi:10.1016/j.transci.2014.02.026
• 32 Moise KJ. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol 2008; 112: 164-176 doi:10.1097/AOG.0b013e31817d453c
• 33 Mari G, Deter RL, Carpenter RL. et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med 2000; 342: 9-14 doi:10.1056/NEJM200001063420102
• 34 Zimmerman R, Carpenter RJ, Durig P. et al. Longitudinal measurement of peak systolic velocity in the fetal middle cerebral artery for monitoring pregnancies complicated by red cell alloimmunisation: a prospective multicentre trial with intention-to-treat. BJOG 2002; 109: 746-752
• 35 van Dongen H, Klumper FJCM, Sikkel E. et al. Non-invasive tests to predict fetal anemia in Kell-alloimmunized pregnancies. Ultrasound Obstet Gynecol 2005; 25: 341-345 doi:10.1002/uog.1821
• 36 ASHP Commission on Therapeutics. ASHP therapeutic guidelines for intravenous immune globulin. Clin Pharm 1992; 11: 117-136
• 37 Heigl F, Hettich R, Arendt R. et al. Immunoadsorption in steroid-refractory multiple sclerosis: clinical experience in 60 patients. Atheroscler Suppl 2013; 14: 167-173 doi:10.1016/j.atherosclerosissup.2012.10.025
• 38 Heigl F, Hettich R. Behandlung der steroidrefraktären multiplen Sklerose – Einsatzgebiet der therapeutischen Apherese. Dialyse aktuell 2015; 19: 198-206 doi:10.1055/s-0035-1554094
• 39 Hoffmann F, Kraft A, Heigl F. et al. Tryptophan-Immunadsorption bei Multipler Sklerose und Neuromyelitis optica: Therapieoption bei akuten Schüben in der Schwangerschaft und Stillphase. Nervenarzt 2015; 86: 179-186 doi:10.1007/s00115-014-4239-8
• 40 Hoffmann F, Kraft A, Heigl F. et al. Tryptophan immunoadsorption during pregnancy and breastfeeding in patients with acute relapse of multiple sclerosis and neuromyelitis optica. Ther Adv Neurol Disord 2018; 11: 1756286418774973 doi:10.1177/1756286418774973
• 41 Thadhani R, Hagmann H, Schaarschmidt W. et al. Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia. J Am Soc Nephrol 2016; 27: 903-913 doi:10.1681/ASN.2015020157
• 42 Easterling TR. Apheresis to Treat Preeclampsia: Insights, Opportunities and Challenges. J Am Soc Nephrol 2016; 27: 663-665 doi:10.1681/ASN.2015070794
• 43 Thung SF, Grobman WA. The cost effectiveness of empiric intravenous immunoglobulin for the antepartum treatment of fetal and neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol 2005; 193 (3 Pt 2): 1094-1099 doi:10.1016/j.ajog.2005.05.048
• 44 Heigl F, Rziha K, Schettler V. et al. Nursing Care Standard in Apheresis – Standard for Therapeutic Apheresis 2017 by the Apheresis Working Group within the German Society of Nephrology and Association of German Kidney Centers e. V. Dialyse aktuell 2017; 21: 405-413