Subscribe to RSS
DOI: 10.1055/a-2464-5009
Die Pathogeninaktivierung zur Gewährleistung einer qualitativ hochwertigen, sicheren und wirtschaftlichen Versorgung mit Thrombozytenkonzentraten in Deutschland
Pathogen Inactivation for Ensuring a High-Quality, Safe, and Cost-effective Supply of Platelet Concentrates in GermanyAuthors
Zusammenfassung
Zielsetzung Die Pathogeninaktivierung (PI) ist ein weltweit anerkanntes Verfahren zur Verbesserung der Sicherheit von Thrombozytenkonzentraten und Plasma. Diese Arbeit untersucht die Notwendigkeit und potenziellen Vorteile der Implementierung der PI für Thrombozytenkonzentrate in Deutschland.
Methodik Analysiert werden sowohl Daten zur aktuellen Blutversorgung als auch zu Infektionsrisiken von Thrombozytenkonzentraten sowie bestehender Sicherheitsstandards auch im interationalen Vergleich.
Ergebnisse Die Ergebnisse zeigen, dass PI die Sicherheit durch die Inaktivierung bekannter und unbekannter Pathogene verbessert, die Haltbarkeit verlängert, den Spenderkreis erweitert und die Anzahl verworfener Thrombozytenkonzentrate reduziert. Dies stabilisiert die Versorgung und senkt Kosten.
Schlussfolgerung Eine Integration der PI in die deutschen Hämotherapie-Richtlinien und beschleunigte Zulassungsverfahren werden empfohlen.
Abstract
Aim Pathogen inactivation (PI) is a globally recognized method for enhancing the safety of platelet concentrates and plasma. This publication examines the necessity and potential benefits of implementing PI for platelet concentrates in Germany.
Method The analysis includes data on the current blood supply, infection risks associated with platelet concentrates, and existing safety standards, also in international comparison.
Results The results show that PI improves safety by inactivating known and unknown pathogens, extends shelf life, expands the donor pool, and reduces the number of discarded platelet concentrates. This stabilizes supply and reduces costs.
Conclusion The integration of PI into the German hemotherapy guideline and accelerated approval processes are recommended.
Schlüsselwörter
Pathogeninaktivierung - Blutversorgung - Transfusionssicherheit - Infektionsrisiko - HämotherapiePublication History
Received: 30 October 2024
Accepted: 05 November 2024
Article published online:
10 December 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
Literatur
- 1 Casper V. Fakten, die für sich sprechen: Blutspende in Zahlen. rnd, 14.06.2020. Im Internet: https://www.rnd.de/gesundheit/lasst-fakten-sprechen-blutspende-in-zahlen-FA2ZCMNO3ZHQVFM33HFHUGJYJQ.html; Stand: 05.07.2024
- 2 BZgA. Am 14. Juni ist Weltblutspendetag. Pressemitteilung der Bundeszentrale für gesundheitliche Aufklärung; 2024
- 3 Greinacher A, Fendrich K, Hoffmann W. Demographic Changes: The Impact for Safe Blood Supply. Transfus Med Hemother 2010; 37: 141-148
- 4 Gesundheitsberichterstattung des Bundes. Verbrauch von Blutprodukten durch Transfusionen (Anzahl von Beuteln). Gliederungsmerkmale: Jahre, Deutschland, Blutprodukte
- 5 Deutscher Bundestag. Spendenaufkommen und Anreize für Blut- und Plasmaspenden in ausgewählten Ländern Spendenaufkommen und Anreize für Blut- und Plasmaspenden in ausgewählten Ländern. WD 9 - 3000 - 007/23 2023
- 6 Oz HS, Westlund KH. "Human babesiosis": an emerging transfusion dilemma. Int J Hepatol 2012; 2012: 431761
- 7 Hong H, Xiao W, Lazarus HM. et al. Detection of septic transfusion reactions to platelet transfusions by active and passive surveillance. Blood 2016; 127: 496-502
- 8 Levy JH, Neal MD, Herman JH. Bacterial contamination of platelets for transfusion: strategies for prevention. Crit Care 2018; 22: 271
- 9 Montgomery SP, Brown JA, Kuehnert M. et al. Transfusion-associated transmission of West Nile virus, United States 2003 through 2005. Transfusion 2006; 46: 2038-2046
- 10 Ghafoor F. Verschmähter Lebensretter: Warum Köln keine Blutspenden aus Ostdeutschland will. Der Tagesspiegel, 26.02.2024. Im Internet: https://www.tagesspiegel.de/wissen/verschmahter-lebensretter-warum-koln-keine-blutspenden-aus-ostdeutschland-will-11248168.html; Stand: 05.07.2024
- 11 Orru' S, Oberle D, Heiden M. et al. Analysis of Transfusion-Transmitted Bacterial Infections according to German Hemovigilance Data (2011-2020). Transfus Med Hemother 2023; 50: 144-153
- 12 Arbeitskreis Blut des Robert-Koch-Instituts. Festlegung der Haltbarkeitsfrist von Thrombozytenkonzentraten mit dem Ziel der Reduktion lebensbedrohlicher septischer Transfusionsreaktionen durch bakterielle Kontamination:. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 2008; 51: 1484
- 13 Jacobs MR, Good CE, Lazarus HM. et al. Relationship between bacterial load, species virulence, and transfusion reaction with transfusion of bacterially contaminated platelets. Clin Infect Dis 2008; 46: 1214-1220
- 14 Himmelsbach K, Mueller S, Kress J. et al. Second hepatitis C virus transmission by blood components since introduction of mandatory NAT screening in Germany. Transfusion 2023; 63: 339-347
- 15 taz. die tageszeitung. Bayerisches Rotes Kreuz bezog Blut aus der DDR. HIV-Test bei Spenderblut erst seit Mai 1985 durchgeführt (10.11.1993). Im Internet: https://taz.de/!1591777/; Stand: 05.07.2024
- 16 Deutscher Bundestag. 3. Untersuchungsausschuss. „HIV-Infektionen durch Blut und Blutprodukte“. Zweite Beschlußempfehlung und Schlußbericht des 3. Untersuchungsausschusses nach Artikel 44 des Grundgesetzes*). Deutscher Bundestag Drucksache. 1994 S. 198, 202
- 17 Prioli KM, Karp JK, Lyons NM. et al. Economic Implications of Pathogen Reduced and Bacterially Tested Platelet Components: A US Hospital Budget Impact Model. Appl Health Econ Health Policy 2018; 16: 889-899
- 18 Lawrence P, Heung M, Nave J. et al. The natural virome and pandemic potential: Disease X. Curr Opin Virol 2023; 63
- 19 Domanović D, Ushiro-Lumb I, Compernolle V. et al. Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting. Blood Transfus 2019; 17: 433-448
- 20 Pierelli L, Vacca M, Zini G. et al. Emergency response of four transfusion centers during the last Chikungunya outbreak in Italy. Transfusion 2018; 58: 3027-3030
- 21 Jutzi M, Mansouri Taleghani B, Rueesch M. et al. Nationwide Implementation of Pathogen Inactivation for All Platelet Concentrates in Switzerland. Transfus Med Hemother 2018; 45: 151-156
- 22 European Directorate for the Quality of Medicines & HealthCare. Blood Supply Contingency and Emergency Plan (B-SCEP) Project. Recommendations Model Preparedness Plan. 2022
- 23 U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research. Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion;. Guidance for Industry [September 2019, updated December 2020]
- 24 Arbeitskreis Blut des Robert-Koch-Instituts. Pathogen-Inaktivierungssysteme für Thrombozytenkonzentrate : Stellungnahme. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 2018; 61: 874-893
- 25 Kleinman S, Reed W, Stassinopoulos A. A patient-oriented risk-benefit analysis of pathogen-inactivated blood components: application to apheresis platelets in the United States. Transfusion 2013; 53: 1603-1618
- 26 Lanteri MC, Santa-Maria F, Laughhunn A. et al. Inactivation of a broad spectrum of viruses and parasites by photochemical treatment of plasma and platelets using amotosalen and ultraviolet A light. Transfusion 2020; 60: 1319-1331
- 27 Pitman JP, Payrat J-M, Park M-S. et al. Longitudinal analysis of annual national hemovigilance data to assess pathogen reduced platelet transfusion trends during conversion to routine universal clinical use and 7-day storage. Transfusion 2023; 63: 711-723
- 28 Mertes PM, Tacquard C, Andreu G. et al. Hypersensitivity transfusion reactions to platelet concentrate: a retrospective analysis of the French hemovigilance network. Transfusion 2020; 60: 507-512
- 29 Paul-Ehrlich-Institut, Henseler O. Bericht des Paul-Ehrlich-Instituts über die nach § 21 Transfusionsgesetz gemeldeten Daten für das Jahr 2020. Auswertung der Meldungen zur Gewinnung von Blut, Blutkomponenten und Stammzellen zur Wiederherstellung des blutbildenden Systems sowie zur Herstellung und zum Verbrauch von Blutprodukten
- 30 Ciaravino V. Preclinical safety of a nucleic acid-targeted Helinx compound: a clinical perspective. Seminars in Hematology 2001; 38: 12-19
- 31 Ciaravino V, McCullough T, Cimino G. et al. Preclinical safety profile of plasma prepared using the INTERCEPT Blood System. Vox Sang 2003; 85: 171-182
- 32 Tice RR, Gatehouse D, Kirkland D. et al. The pathogen reduction treatment of platelets with S-59 HCl (Amotosalen) plus ultraviolet A light: genotoxicity profile and hazard assessment. Mutat Res 2007; 630: 50-68
- 33 Vallance TM, Zeuner M-T, Williams HF. et al. Toll-Like Receptor 4 Signalling and Its Impact on Platelet Function, Thrombosis, and Haemostasis. Mediators Inflamm 2017; 2017: 9605894
- 34 Amato M, Schennach H, Astl M. et al. Impact of platelet pathogen inactivation on blood component utilization and patient safety in a large Austrian Regional Medical Centre. Vox Sang 2017; 112: 47-55
- 35 Nussbaumer W, Amato M, Schennach H. et al. Patient outcomes and amotosalen/UVA-treated platelet utilization in massively transfused patients. Vox Sang 2017; 112: 249-256
- 36 Bonn J, Baltin CT, Osterkamp V. et al. Health Economic Aspects of Platelet Concentrates: Comparing Cost and Reimbursement of Pathogen Inactivated and Conventional Platelet Concentrates in a German Comprehensive Cancer Center. Oncol Res Treat 2023; 46: 362-369
- 37 Dierks+Company. Rechtliches Memorandum zur medizinischen Sorgfalt im Kontext der Pathogen-Inaktivierung [wird auf Anfrage zur Verfügung gestellt]; 4.March.2024
- 38 Giménez-Richarte Á, Ortiz de Salazar MI, Giménez-Richarte M-P. et al. Transfusion-transmitted arboviruses: Update and systematic review. PLoS Negl Trop Dis 2022; 16: e0010843
- 39 Cazenave J-P, Isola H, Waller C. et al. Use of additive solutions and pathogen inactivation treatment of platelet components in a regional blood center: impact on patient outcomes and component utilization during a 3-year period. Transfusion 2011; 51: 622-629
- 40 Norris PJ, Kaidarova Z, Maiorana E. et al. Ultraviolet light-based pathogen inactivation and alloimmunization after platelet transfusion: results from a randomized trial. Transfusion 2018; 58: 1210-1217
- 41 Richard P, Pouchol E, Sandid I. et al. Implementation of amotosalen plus ultraviolet A-mediated pathogen reduction for all platelet concentrates in France: Impact on the risk of transfusion-transmitted infections. Vox Sang 2024; 119: 212-218
- 42 Fadeyi EA, Wagner SJ, Goldberg C. et al. Fatal sepsis associated with a storage container leak permitting platelet contamination with environmental bacteria after pathogen reduction. Transfusion 2021; 61: 641-648
- 43 Brixner V, Bug G, Pohler P. et al. Efficacy of UVC-treated, pathogen-reduced platelets versus untreated platelets: a randomized controlled non-inferiority trial. Haematologica 2021; 106: 1086-1096
- 44 Leitner GC, Ho M, Tolios A. et al. The assessment of platelet function by thromboelastometry as a point-of-care test to guide Intercept-treated platelet support in hemato-oncological patients and hematopoietic stem cell transplantation recipients. Transfusion 2020; 60: 1391-1399
- 45 Cap AP, Pidcoke HF, Keil SD. et al. Treatment of blood with a pathogen reduction technology using ultraviolet light and riboflavin inactivates Ebola virus in vitro. Transfusion 2016; 56: 6-15
- 46 McDonald CP, Bearne J, Aplin K. et al. Assessing the inactivation capabilities of two commercially available platelet component pathogen inactivation systems: effectiveness at end of shelf life. Vox Sang 2021; 116: 416-424
- 47 Kwon SY, Kim IS, Bae JE. et al. Pathogen inactivation efficacy of Mirasol PRT System and Intercept Blood System for non-leucoreduced platelet-rich plasma-derived platelets suspended in plasma. Vox Sang 2014; 107: 254-260
- 48 Cid J, Charry P, Lozano M. Therapeutic efficacy and safety of pathogen-reduced platelet components: Results of a meta-analysis of randomized controlled trials. Vox Sang 2024; 119: 203-211
- 49 Hechler B, Ohlmann P, Chafey P. et al. Preserved functional and biochemical characteristics of platelet components prepared with amotosalen and ultraviolet A for pathogen inactivation. Transfusion 2013; 53: 1187-1200
- 50 Arnason NA, Johannson F, Landrö R. et al. Pathogen inactivation with amotosalen plus UVA illumination minimally impacts microRNA expression in platelets during storage under standard blood banking conditions. Transfusion 2019; 59: 3727-3735
- 51 Prax M, Bekeredjian-Ding I, Krut O. Microbiological Screening of Platelet Concentrates in Europe. Transfus Med Hemother 2019; 46: 76-86
- 52 Kaur B, Kumar S, Kaushik BK. Trends, challenges, and advances in optical sensing for pathogenic bacteria detection (PathoBactD). Biosensors and Bioelectronics: X 2023; 14: 100352
- 53 Rios J, Webb J, Dy B. et al. The operational and financial impact of adding anaerobic screening of platelets. Transfusion 2024; 64: 104-115
- 54 Walker BS, White SK, Schmidt RL. et al. Residual bacterial detection rates after primary culture as determined by secondary culture and rapid testing in platelet components: A systematic review and meta-analysis. Transfusion 2020; 60: 2029-2037
- 55 Walker BS, Schmidt RL, White SK. et al. Meta-analysis of bacterial growth characteristics in platelet components: Refining the inputs of a simulation analysis comparing the relative safety of testing strategies. Transfusion 2023; 63: 1719-1727
- 56 Austria: Bundesamt für Sicherheit im Gesundheitswesen (BASG), Hämovigilanz -Bericht 2022, https://www.basg.gv.at/fileadmin/redakteure/04_Marktbeobachtung/H%C3%A4movigilanz/Haemovigilanz_Bericht_2022.pdf?sword_list%5B0%5D=H%C3%A4movigilanz_2022
- 57 Belgium: Advies van de hoge gezondheidsraad Nr.8700, De Klinische doeltreffendheid van pathogeen reuctie met het oog op de implementatie voor bloedplaatjesconcentraten, 1 juni 2011, https://www.health.belgium.be/sites/default/files/uploads/fields/fpshealth_theme_file/19069728/De%20klinische%20doeltreffendheid%20van%20pathogeenreductie%20met%20het%20oog%20op%20implementatie%20voor%20bloedplaatjesconcentraten%20%28juni%202011%29%20%28HGR%208700%29.pdf
- 58 Denmark: Marcel Prax, Microbiological Screening of Platelet Concentrates in Europe, Transfus Med Hemother 2019 Apr, 46(2): 76-8
- 59 France: P. Richard, Implementation of amotosalen plus ultraviolet A -mediated pathogen reduction for all platelet concentrates in france: Impact on the risk of transfusion -transmitted infections, Vox Sanguinis, 2023, 1–7
- 60 Iceland: Impact of Pl on outdating rates and supply continuity, 1st Nordics Seminar on Blood Safety and Pathogen Inactivation, December 2021, Stockholm, https://info.interceptbloodsystem.com/en/impact-pi-on-outdating-rates-and-supply-continuity_landro?hsCtaTracking=d09dcabc-610b-447f-87dc-9eb58d917dd8%7Cb40243fc-6afa-4fe7-9460-242842362465
- 61 Ireland: Marcel Prax, Microbiological Screening of Platelet Concentrates in Europe, Transfus Med Hemother 2019 Apr, 46(2): 76-8
- 62 Luxembourg: Malvaux N. In Vitro Comparative Study of Platelets Treated with Two Pathogen -Inactivation Methods to Extend Shelf Life to 7 Days. Pathogens 2022; 11: 343
- 63 Netherlands: Marcel Prax, Microbiological Screening of Platelet Concentrates in Europe, Transfus Med Hemother 2019 Apr, 46(2): 76-8
- 64 Norway: Thanh Hoang, Blodtransfusjonstjenesten i Norge, Statistikk for 2021, https://www.helsedirektoratet.no/rapporter/transfusjonsstatistikk/Transfusjonsstatistikk%202021.pdf/_/attachment/inline/543fa83a-3e87-4639-bcda-830862907d6a:258c9a56d090b67f72042fc36ad8b2056f9f5284/Transfusjonsstatistikk%202021.pdf
- 65 Slovenia Domanovic D. Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting. Blood Transfus 2019; 17: 433-448
- 66 Switzerland: M. Jutzi Nationwide Implementation of Pathogen Inactivation for all Platelet concentrates in Switzerland. Transfusion Medicine and Hemotherapy 2018;45 -151-156
- 67 United Kingdom: Annual Serious Hazards of Transfusion (SHOT) 2022, https://pubmed.ncbi.nlm.nih.gov/29799121/
- 68 Sweden: A Alshamari, Platelet Safety Measures in Sweden: An Assessment of Current Practices and Comparison with International Practices, Poster ISBT 2023, https://www.sweba.se/post/uppdaterad-statistik-samt-bilder-f%C3%B6r-visning
- 69 Portugal https://europeanbloodalliance.eu/country/portugal/
- 70 Spain: Sistema Nacional para la Seguridad Transfusioanl, Actividad centros Y Servicios Transfusión 2021, https://www.sanidad.gob.es/profesionales/saludPublica/medicinaTransfusional/publicaciones/docs/informeActividad2021.pdf
- 71 Lithuania: VIEŠOSIOS ĮSTAIGOS NACIONALINIO KRAUJO CENTRO 2022 METŲ VEIKLOS ATASKAITA, https://www.registrucentras.lt/jar/paieska/edoc_fa.php?enc=DBHCBzAxh5obI8alD5I7VVDD0W4ed3PPDIyTq8PZV7aVTs1JDnkHLmRpQ5Q8XSsjy8CgPvN43ILdkyTH4jzb%2FnDLOmgmLXqQycHBabbUyqmTOrgrS7l3r3MTQeOrLXSPCL2NEDXuEV37M10dp3I8Qsg7BXrSqvlV5TXL4iYndIG8%2Bgk%3D
- 72 Poland Rosiek A. Blood transfusion Service in Poland in 2022. Journal of Transfusion Medicine 2023; Vol 16 no.4 167-188
- 73 Croatia: Hrvatski Zavod Za Transfuzijsku Medicinu; Dokumenti
- 74 Latvia: Valsts Asinsdonoru Centra; Publiskais Parskatz 20222.GADS, https://www.vadc.gov.lv/lv/media/2256/download?attachment
- 75 Italy: L. Catalone, Italian Blood system 2021: activity data, haemovigilance and epidemiological surveillance, Istituto superiore di sanita, https://www.centronazionalesangue.it/wp-content/uploads/2022/11/22-25-web.pdf
- 76 Slovakia: Workshop Moving towards optimal blood Safety and Supply Continuity for Vulnerable Patients, Oct. 2023; Implementing pathogen inactivation technology in the Slovakian National Transfusion Services (SNTS); Dr. Kristina Fejdová
- 77 Greece: Έκθεση περί της Αιμοδοσίας για το έτος 2023, https://ekea.gr/wp-content/uploads/%CE%97-%CE%88%CE%BA%CE%B8%CE%B5%CF%83%CE%B7-%CE%B3%CE%B9%CE%B1-%CF%84%CE%B7%CE%BD-%CE%91%CE%B9%CE%BC%CE%BF%CE%B4%CE%BF%CF%83%CE%AF%CE%B1-2023.pdf
- 78 Germany: Bericht des Paul-Ehrlich-Instituts uber die nach $21 transfusionsgesetz gemeldeten daten// Bericht für das Jahr 2022, https://www.pei.de/SharedDocs/Downloads/DE/regulation/meldung/21-tfg/21-tfg-berichte/2022-tfg-21-bericht.pdf?__blob=publicationFile&v=2
- 79 Czech Republic Domanovic D. Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting. Blood Transfus. 2019 17. 433-448
- 80 Finland Domanovic D. Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting. Blood Transfus 2019; 17: 433-448
- 81 Hungary Domanovic D. Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting. Blood Transfus 2019; 17: 433-448
- 82 Romania Domanovic D. Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting. Blood Transfus 2019; 17: 433-448
- 83 Bericht des Paul-ehrlich-Instituts über die nach § 21 Transfusionsgesetz gemeldeten Daten 2020. Version 2 vom 03.11.2021
- 84 Prioli KM. et al. Economic Implications of Pathogen Reduced and Bacterially Tested Platelet Components: A US Hospital Budget Impact Model. Appl. Health Econ Health Policy 2018; 6: 889-899
- 85 ANSM Meeting minutes: Public health Code (SP) Drug Safety and Quality Restricted training on viral and microbiological safety. SCIENT_FOR08 V03 (02/06/2020) https://ansm.sante.fr/evenements/comite-securite-et-qualite-des-medicaments-formation-restreinte-securite-virale-et-securte-microbiologique-2 Formation restreinte sécurité virale et sécurité microbiologique – Ordre du jour (21/07/2020) Compte-rendu (25/09/2020)
- 86 5days PLT in PLS and 7 days in PLT in PAS. Approval with post-marketing commitment. Summary of the Risk Management Plan (RMP) for Mirasol System for Platelets (Mirasol-treated Platelets) Version 1.0 (October 2020)
- 87 TERUMO, Health Canada Approves Mirasol Pathogen Reduction Technology System to Treat Platelets in Plasma (08/18/2021). https://www.terumobct.com/Pages/News/Press%20Releases/Health-Canada-Approves-Mirasol-Pathogen-Reduction-Technology-System--to-Treat-Platelets-in-Plasma.aspx
