Rationale Therapie mit Erythrozytenkonzentraten – Update 2020

Zusammenfassung

Der Einsatz von Erythrozytenkonzentraten muss dem Gebot einer rationalen Indikation folgen. Um dies weiter zu gewährleisten, wurden die 2009 publizierten und zuletzt 2014 in Teilen revidierten „Querschnitts-Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten“ [1] der Bundesärztekammer 2020 einer systematischen Novellierung unterzogen. Der Artikel stellt sie vor.

Abstract

The use of erythrocyte concentrates (EK) must be based on a rational indication. In order to insure this, the guidelines of the German Medical Association published in 2009 and last revised in part in 2014 were subject to a systematic amendment in 2020. The clinical studies published in the past few years confirmed the basic statements of the guidelines on erythrocyte transfusion for an individually adapted but fundamentally restrictive indication. At the same time, the results of new studies on defined patient groups made it possible to further individualize the indication for erythrocyte transfusion. The indication for erythrocyte transfusion must align with the question how it is possible to compensate for anaemic oxygen deficiency in the individual case. Clinical symptoms of anaemic hypoxia that occur when the oxygen supply falls below a critical level (so-called “physiological transfusion triggers”) are the definitive indicators of erythrocyte transfusion. However, these are unspecific and cannot always be clearly determined under clinical conditions. Therefore, the current haemoglobin concentration, the general condition and those concomitant diseases that limit the individualʼs ability to compensate for anaemia must be taken into account when setting the individual indication for erythrocyte transfusion.

Kernaussagen

• Der Einsatz von Erythrozytenkonzentraten (EK) muss dem Gebot einer rationalen Indikation folgen. Um dies weiter zu gewährleisten, wurden die „Querschnitts-Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten“ 2020 einer systematischen Novellierung unterzogen.

• Die in den vergangenen Jahren publizierten klinischen Studien bestätigten die seinerzeitigen Grundaussagen der Leitlinien zur Erythrozytentransfusion für eine individuell angepasste, grundsätzlich aber restriktive Indikationsstellung.

• Gleichzeitig ermöglichten die Ergebnisse neuer Studien an definierten Patientengruppen eine weitere Individualisierung der Indikationsstellung zur Erythrozytentransfusion.

• Für die Indikation zur Erythrozytentransfusion bleibt maßgeblich, wie es im individuellen Fall gelingt, einen anämisch bedingten Sauerstoffmangel zu kompensieren.

• Klinische Symptome der anämischen Hypoxie, die beim Unterschreiten eines kritischen Sauerstoffangebots auftreten, sog. „physiologische Transfusionstrigger“, sind streng genommen die definitiven Indikatoren zur Erythrozytentransfusion. Allerdings sind diese unspezifisch und unter klinischen Bedingungen nicht immer eindeutig zu bestimmen.

• Daher müssen bei der individuellen Indikationsstellung zur Erythrozytentransfusion die aktuelle Hämoglobinkonzentration, der Allgemeinzustand und solche Begleiterkrankungen mitbeachtet werden, welche die individuelle Fähigkeit, eine Anämie zu kompensieren, limitieren.

• Darüber hinaus müssen Ergebnisse klinischer Studien in vergleichbaren Patientengruppen in die Entscheidungsfindung mit einfließen.

• Auch die neueren klinische Studien und die darauf basierende Leitlinien bestätigen, dass bei moderater akuter und chronischer Anämie (Hämoglobin [Hb] 7 – 10 g/dl) die meisten Patienten hinsichtlich ihrer Langzeitprognose nicht von Erythrozytentransfusionen profitieren.

Schlüsselwörter

Erythrozytenkonzentrat - Anämie - hypoxische Anämie - Transfusionsindikation - Kompensationsmechanismen der Anämie

Key words

red cell concentrates - anaemia - hypoxic anaemia - transfusion indication - compensation mechanisms for anaemia

Publication History

Article published online:
17 February 2021

• Literatur

• 1 Bundesärztekammer. Querschnitts-Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten – Gesamtnovelle 2020. Köln: Deutscher Ärzteverlag; 2020
• 2 Bundesärztekammer im Einvernehmen mit dem PEI. Richtlinie zur Gewinnung von Blut und Blutbestandteilen und zur Anwendung von Blutprodukten (Richtlinie Hämotherapie). Gesamtnovelle 2017 mit Erratum und Anpassungen. Köln: Deutscher Ärzteverlag; 2019
• 3 Hébert PC, Van der Linden P, Biro G. et al. Physiologic aspects of anemia. Crit Care Clin 2004; 20: 187-212.ccc.2004.01.001 doi:10.1016/j
• 4 Hébert PC, Martin C, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999; 340: 409-417
• 5 Holst LB, Haase N, Wetterslev J. et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 2014; 371: 1381-1391 doi:10.1056/NEJMoa1406617
• 6 Mazer CD, Whitlock RP, Fergusson DA. et al. Restrictive or liberal red-cell transfusion for cardiac surgery. N Engl J Med 2017; 377: 2133-2144 doi:10.1056/NEJMoa1711818
• 7 Carson JL, Terrin ML, Noveck H. et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011; 365: 2453-2462 doi:10.1056/NEJMoa1012452
• 8 Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med 2008; 36: 2667-2674 doi:10.1097/CCM.0b013e3181844677
• 9 Glance LG, Dick AW, Mukamel DB. et al. Association between intraoperative blood transfusion and mortality and morbidity in patients undergoing noncardiac surgery. Anesthesiology 2011; 114: 283-292 doi:10.1097/ALN.0b013e3182054d06
• 10 Meybohm P, Richards T, Isbister J. et al. Patient blood management bundles to facilitate implementation. Transfus Med Rev 2017; 31: 62-71 doi:10.1016/j.tmrv.2016.05.012
• 11 Mueller MM, Van Remoortel H, Meybohm P. et al. Patient blood management: recommendations from the 2018 Frankfurt Consensus Conference. JAMA 2019; 321: 983 doi:10.1001/jama.2019.0554
• 12 Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin e. V.. S3-Leitlinie Perioperative Anämie: Diagnostik und Therapie der präoperativen Anämie. AWMF Registernummer 001–0024 (2018). Im Internet (Stand: 25.01.2021): https://www.awmf.org/leitlinien/detail/ll/001-024.html
• 13 National Health and Medical Research Council, National Blood Authority (Australia). Patient blood management guidelines. Obstetrics and maternity. Obstet Maternity 2015. Im Internet (Stand 08.02.2021): https://www.blood.gov.au/pbm-module-5
• 14 Leahy MF, Hofmann A, Towler S. et al. Improved outcomes and reduced costs associated with a health-system-wide patient blood management program: a retrospective observational study in four major adult tertiary-care hospitals: patient blood management outcomes. Transfusion 2017; 57: 1347-1358 doi:10.1111/trf.14006
• 15 Meybohm P, Herrmann E, Steinbicker AU. et al. Patient Blood management is associated with a substantial reduction of red blood cell utilization and safe for patientʼs outcome: a prospective, multicenter cohort study with a noninferiority design. Ann Surg 2016; 264: 203-211 doi:10.1097/SLA.0000000000001747
• 16 Valeri CR, Dennis RC, Ragno G. et al. Limitations of the hematocrit level to assess the need for red blood cell transfusion in hypovolemic anemic patients. Transfusion 2006; 46: 365-371 doi:10.1111/j.1537-2995.2006.00730.x
• 17 Carson JL, Stanworth SJ, Roubinian N. et al. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev 2016; (10) CD002042 DOI: 10.1002/14651858.CD002042.pub4.
• 18 Carson JL, Stanworth SJ, Alexander JH. et al. Clinical trials evaluating red blood cell transfusion thresholds: An updated systematic review and with additional focus on patients with cardiovascular disease. Am Heart J 2018; 200: 96-101 doi:10.1016/j.ahj.2018.04.007
• 19 Brunskill SJ, Millette SL, Shokoohi A. et al. Red blood cell transfusion for people undergoing hip fracture surgery. Cochrane Database Syst Rev 2015; (04) CD009699 DOI: 10.1002/14651858.CD009699.pub2.
• 20 Mitchell MD, Betesh JS, Ahn J. et al. Transfusion thresholds for major orthopedic surgery: a systematic review and meta-analysis. J Arthroplast 2017; 32: 3815-3821 doi:10.1016/j.arth.2017.06.054
• 21 Docherty AB, OʼDonnell R, Brunskill S. et al. Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis. BMJ 2016; 352: i1351 doi:10.1136/bmj10.1136/bmj.i1351
• 22 Gu W-J, Gu X-P, Wu X-D. et al. Restrictive versus liberal strategy for red blood-cell transfusion: a systematic review and meta-analysis in orthopaedic patients. J Bone Joint Surg Am 2018; 100: 686-695 doi:10.2106/JBJS.17.00375
• 23 Simon GI, Craswell A, Thom O. et al. Outcomes of restrictive versus liberal transfusion strategies in older adults from nine randomised controlled trials: a systematic review and meta-analysis. Lancet Haematol 2017; 4: e465-e474 doi:10.1016/S2352-3026(17)30141-2
• 24 Carson JL, Brooks MM, Abbott JD. et al. Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J 2013; 165: 964-971 doi:10.1016/j.e1.ahj.2013.03.001
• 25 Cooper HA, Rao SV, Greenberg MD. et al. Conservative versus liberal red cell transfusion in acute myocardial infarction (the CRIT Randomized Pilot Study). Am J Cardiol 2011; 108: 1108-1111 doi:10.1016/j.amjcard.2011.06.014
• 26 Hajjar LA, Vincent J-L, Galas FRBG. et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA 2010; 304: 1559-1567 doi:10.1001/jama.2010.1446
• 27 Mazer CD, Whitlock RP, Fergusson DA. et al. Six-month outcomes after restrictive or liberal transfusion for cardiac surgery. N Engl J Med 2018; 379: 1224-1233 doi:10.1056/NEJMoa1808561
• 28 Murphy GJ, Pike K, Rogers CA. et al. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015; 372: 997-1008 doi:10.1056/NEJMoa1403612
• 29 Jairath V, Kahan BC, Gray A. et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet 2015; 386: 137-144 doi:10.1016/S0140-6736(14)61999-1
• 30 Villanueva C, Colomo A, Bosch A. et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368: 11-21 doi:10.1056/NEJMoa1211801
• 31 Mak LY, Lau CW, Hui YT. et al. Joint recommendations on management of anaemia in patients with gastrointestinal bleeding in Hong Kong. Hong Kong Med J 2018; 24: 416-422 doi:10.12809/hkmj187348
• 32 Odutayo A, Desborough MJR, Trivella M. et al. Restrictive versus liberal blood transfusion for gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials. Lancet Gastroenterol Hepatol 2017; 2: 354-360 doi:10.1016/S2468-1253(17)30054-7
• 33 Ayling OGS, Ibrahim GM, Alotaibi NM. et al. Anemia after aneurysmal subarachnoid hemorrhage is associated with poor outcome and death. Stroke 2018; 49: 1859-1865 doi:10.1161/STROKEAHA.117.020260
• 34 S3 Leitlinie Polytrauma. Schwerverletzten-Behandlung. AWMF Register-Nr. 012-019. Im Internet (Stand: 16.06.2020): https://www.awmf.org/leitlinien/detail/ll/012-019.html
• 35 Kozek-Langenecker SA, Ahmed AB, Afshari A. et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2017; 34: 332-395 doi:10.1097/EJA.0000000000000630
• 36 Webb J. Social aspects of chronic transfusions: addressing social determinants of health, health literacy, and quality of life. Hematology. Am Soc Hematol Educ Program 2020; 2020: 175-183
• 37 Wood EM, McQuilten ZK. Outpatient transfusions for myelodysplastic syndromes. Hematology. Am Soc Hematol Educ Program 2020; 2020: 167-174
• 38 Hochsmann B, Moicean A, Risitano A. et al. Supportive care in severe and very severe aplastic anemia. Bone Marrow Transplant 2013; 48: 168-173
• 39 Yakymenko D, Frandsen KB, Christensen IJ. et al. Randomised feasibility study of a more liberal haemoglobin trigger for red blood cell transfusion compared to standard practice in anaemic cancer patients treated with chemotherapy. Transfus Med 2018; 28: 208-215
• 40 Chin-Yee N, Taylor J, Rourke K. et al. Red blood cell transfusion in adult palliative care: a systematic review. Transfusion 2018; 58: 233-241
• 41 Stanworth SJ, Killick S, McQuilten ZK. et al. Red cell transfusion in outpatients with myelodysplastic syndromes: a feasibility and exploratory randomised trial. Br J Haematol 2020; 189: 279-290
• 42 Greenberg PL, Stone RM, Al-Kali A. et al. Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2017; 15: 60-87
• 43 Malcovati L, Hellstrom-Lindberg E, Bowen D. et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood 2013; 122: 2943-2964
• 44 Killick SB, Carter C, Culligan D. et al. Guidelines for the diagnosis and management of adult myelodysplastic syndromes. Br J Haematol 2014; 164: 503-525
• 45 Estcourt LJ, Malouf R, Trivella M. et al. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Syst Rev 2017; (01) CD011305
• 46 Prescott LS, Taylor JS, Lopez-Olivo MA. et al. How low should we go: A systematic review and meta-analysis of the impact of restrictive red blood cell transfusion strategies in oncology. Cancer Treat Rev 2016; 46: 1-8
• 47 Lightdale JR, Randolph AG, Tran CM. et al. Impact of a conservative red blood cell transfusion strategy in children undergoing hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2012; 18: 813-817
• 48 Robitaille N, Lacroix J, Alexandrov L. et al. Excess of veno-occlusive disease in a randomized clinical trial on a higher trigger for red blood cell transfusion after bone marrow transplantation: a canadian blood and marrow transplant group trial. Biol Blood Marrow Transplant 2013; 19: 468-473
• 49 Tay J, Allan DS, Chatelein E. et al. Transfusion of red cells in hematopoietic stem cell transplantation (trist study): a randomized controlled trial evaluating 2 red cell transfusion thresholds [abstract]. Blood 2016; 128: 1032
• 50 Tonia T, Mettler A, Robert N. et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev 2012; (12) CD003407
• 51 Gao S, Ma JJ, Lu C. Venous thromboembolism risk and erythropoiesis-stimulating agents for the treatment of cancer-associated anemia: a meta-analysis. Tumour Biol 2014; 35: 603-613
• 52 Bohlius J, Bohlke K, Castelli R. et al. Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update. Blood Adv 2019; 3: 1197-1210
• 53 Deutsche Krebsgesellschaft, Deutsche Gesellschaft für Hämatologie und medizinische Onkologie, and Deutsche Gesellschaft für Radioonkologie. S3-Leitlinie Supportive Therapie bei onkologischen PatientInnen. 2019. AWMF Registriernummer: 032/054OL. Im Internet (Stand: 25.01.2021): https://www.awmf.org/leitlinien/detail/ll/032-054OL.html
• 54 Estcourt LJ, Fortin PM, Hopewell S. et al. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease. Cochrane Database Syst Rev 2017; (01) CD003146
• 55 Fortin PM, Hopewell S, Estcourt LJ. Red blood cell transfusion to treat or prevent complications in sickle cell disease: an overview of Cochrane reviews. Cochrane Database Syst Rev 2018; (08) CD012082
• 56 Cario H, Kohne E, Creutzig U, Lehrnbecher T. Leitlinie AWMF 025/017 Thalassämie (2016). Im Internet (Stand: 25.01.2021): https://www.awmf.org/leitlinien/detail/ll/025-017.html
• 57 Lal A. Challenges in chronic transfusion for patients with thalassemia. Hematology. Am Soc Hematol Educ Program 2020; 2020: 160-166
• 58 Chou ST, Alsawas M, Fasano RM. et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv 2020; 4: 327-355
• 59 New HV, Berryman J, Bolton-Maggs PHB. et al. Guidelines on transfusion for fetuses, neonates and older children. Br J Haematol 2016; 175: 784-828 doi:10.1111/bjh.14233
• 60 de Gast-Bakker DH, de Wilde RBP, Hazekamp MG. et al. Safety and effects of two red blood cell transfusion strategies in pediatric cardiac surgery patients: a randomized controlled trial. Intensive Care Med 2013; 39: 2011-2019 doi:10.1007/s00134-013-3085-7
• 61 Lacroix J, Hébert PC, Hutchison JS. et al. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 2007; 356: 1609-1619 doi:10.1056/NEJMoa066240
• 62 Madsen LP, Rasmussen MK, Bjerregaard LL. et al. Impact of blood sampling in very preterm infants. Scand J Clin Lab Invest 2000; 60: 125-132 doi:10.1080/00365510050184949
• 63 Roseff SD, Luban NLC, Manno CS. Guidelines for assessing appropriateness of pediatric transfusion. Transfusion 2002; 42: 1398-1413 doi:10.1046/j.1537-2995.2002.00208.x
• 64 Franz AR, Engel C, Bassler D. et al. Effects of liberal vs. restrictive transfusion thresholds on survival and neurocognitive outcomes in extremely low-birth-weight infants: The ETTNO randomized clinical trial. JAMA 2020; 324: 560-570 doi:10.1001/jama.2020.10690