Patient Blood Management E-Book

Hans Gombotz

• Herausgeber: Thieme
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 752

Veröffentlichungsjahr: 2015

Beschreibung

Patient Blood Management (PBM) is an innovative clinical concept that aims to reduce the need for allogenic blood transfusions, cut health-care costs, and avert or correct the risk factors related to blood transfusion, thus minimizing the rate of side effects and complications. This comprehensive hands-on volume offers a three-point approach for the implementation of PBM to improve patient outcome, focusing on how to prevent or treat anemia, reduce blood loss, and increase anemia tolerance. The book also goes beyond preoperative PBM, with detailed accounts of coagulation disorder management and the administration of coagulation products and platelet concentrates.

Special Features:

• Presents a clear three-pillar strategy for the application of PBM: diagnosis and treatment of anemia, reduction of peri-interventional blood loss, and optimization of the tolerance to anemia in the everyday clinical setting
• Covers issues such as PBM during surgery, requirements for modern transfusion medicine, ordering blood products, the role of pre-anesthesia clinics, benchmarking processes, and potential implications of PBM in the public health sector
• Overview of research in PBM including landmark studies and current clinical trials
• Boxes in each chapter highlighting key information, core statements, and summaries
• A multidisciplinary and international team of contributors experienced in PBM

Patient Blood Management is a guide for clinicians and residents whose patients are at risk for anemia, coagulation disorders, or severe blood loss. Anesthesiologists, surgeons, and specialists involved in the use of blood and blood products can use the book for quick reference or to learn more about a leading-edge concept for optimizing patient safety and improving outcome.

Leseprobe

Patient Blood Management

Hans Gombotz, MDProfessorFormer Chairman of the Department of Anesthesiology and Intensive Care MedicineGeneral Hospital LinzLinz, Austria

Kai Zacharowski, MD, PhD, FRCAProfessor and ChairmanDepartment of AnesthesiologyIntensive Care Medicine and Pain TherapyUniversity Hospital FrankfurtFrankfurt am Main, Germany

Donat Rudolf Spahn, MD, FRCAProfessor and ChairmanInstitute of AnesthesiologySection Head Medical Anesthesiology—Intensive Care Medicine—OR ManagementUniversity of Zurich and University Hospital ZurichZurich, Switzerland

44 illustrations

ThiemeStuttgart · New York · Delhi · Rio de Janeiro

Library of Congress Cataloging-in-Publication Data is available from the publisher.

Twenty one subchapters have been previously published in the German language in the following publication: Patient Blood Management published and copyrighted 2013 by Georg Thieme Verlag, Stuttgart.

Translator: Sarah Venkata, London, UK

Illustrator: Angelika Brauner, Hohenpeißenberg, Germany

© 2016 Georg Thieme Verlag KG

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Printed in Germany by AZ Druck und Datentechnik, Kempten

ISBN 978-3-13-200441-2                         5  4  3  2  1

Also available as an e-book: eISBN 978-3-13-200451-1

Important note: Medicine is an ever-changing science undergoing continual development. Research and clinical experience are continually expanding our knowledge, in particular our knowledge of proper treatment and drug therapy. Insofar as this book mentions any dosage or application, readers may rest assured that the authors, editors, and publishers have made every effort to ensure that such references are in accordance with the state of knowledge at the time of production of the book.

Nevertheless, this does not involve, imply, or express any guarantee or responsibility on the part of the publishers in respect to any dosage instructions and forms of applications stated in the book. Every user is requested to examine carefully the manufacturers’ leaflets accompanying each drug and to check, if necessary in consultation with a physician or specialist, whether the dosage schedules mentioned therein or the contraindications stated by the manufacturers differ from the statements made in the present book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market. Every dosage schedule or every form of application used is entirely at the user’s own risk and responsibility. The authors and publishers request every user to report to the publishers any discrepancies or inaccuracies noticed. If errors in this work are found after publication, errata will be posted at www.thieme.com on the product description page.

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This book, including all parts thereof, is legally protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by copyright legislation, without the publisher’s consent, is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, mimeographing, preparation of microfilms, and electronic data processing and storage.

Contents

1 Introduction

1.1 PBM: A Concept to Improve Patient Safety and Outcome

H. Gombotz, A. Hofmann

1.2 Requirements of Modern Transfusion Medicine

C. Geisen, M. M. Mueller, E. Seifried

1.3 Transfusion and Patient Outcomes

S. Farmer, A. Hofmann, J. Isbister

1.4 Outcomes after Platelet Transfusion

B. D. Spiess

1.5 Use of Plasma in PBM—Effectiveness and Outcomes

A. Shander, M. Javidroozi

1.6 Key Role of Benchmarking Processes in PBM

A. Hofmann, S. Farmer

2 Practical Aspects of Preoperative Patient Management

2.1 Role of the Preanesthesia Assessment Clinic in Patient Blood Management

G. Fritsch

2.2 Role of the General Practitioner

J. Steinhaeuser, T. Kuehlein

2.3 Calculation of the Transfusion Probability—the Mercuriali Algorithm

P. H. Rehak

2.4 Ordering Procedures for Blood Products

A. Weigl

3 First Pillar of PBM—Optimization of the Red Blood Cell Volume

3.1 Definition, Diagnosis, and Consequences of Preoperative Anemia

G. Lanzer

3.2 Pros and Cons of Preoperative Anemia Treatment

P. Meybohm, K. Zacharowski

4 Second Pillar of PBM—Minimization of Bleeding and Blood Loss

4.1 Reduction of Diagnostic and Interventional Blood Loss

H. Gombotz

4.2 Coagulation Management

C. F. Weber, K. Zacharowski

4.3 Use of Allogeneic Blood Conservation Strategies

C. von Heymann, L. Kaufner

4.4 Surgical Technique and Minimally Invasive Surgery—Limitations and Prospects

J. W. Erhard

4.5 Local and Systemic Promotion of Perioperative Hemostasis

J. W. Erhard

5 Third Pillar of PBM—Harnessing and Optimization of the Patient’s Physiological Tolerance to Anemia

5.1 Perioperative Optimization of the Anemia Tolerance

J. Meier, K. Zacharowski

5.2 Determinants of the Decision to Transfuse Red Blood Cells

D. Meininger, K. Zacharowski

5.3 Functions of Circulating Blood Other Than Oxygen Transport

B. Friesenecker

5.4 Management of Profound Anemia in Patients Refusing Red Blood Cell Transfusion

P. Van der Linden

6 PBM in Surgical Settings

6.1 PBM in Cardiac Surgery

H. M. Mueller

6.2 PBM in Pediatric Cardiac Surgery

J. Meier, R. Mair

6.3 PBM in Trauma Surgery

J. M. Hamdorf

6.4 PBM in Gynecology

J. J. Lee

6.5 PBM in Orthopaedic Surgery

A. Kotze

6.6 PBM in Vascular Surgery

B. Clevenger, T. Richards

7 PBM in Nonsurgical Settings

7.1 Potential for PBM in Intensive Care Medicine

M. Hiesmayr, A. Schiferer

7.2 Potential for PBM in Oncology and Hematology

M. Fridrik

7.3 Potential for PBM in Cardiology

R. Goldweit

8 Practical Implementation of PBM and Outlook

8.1 PBM and Outcome

D. R. Spahn

8.2 Establishment of PBM in Teaching and Practice

A. Hofmann, H. Gombotz

8.3 The Australian PBM Concept—a Success Story

S. L. Farmer, S. Towler, A. Hofmann

8.4 Landmark Studies and Current Clinical Trials in the Field of PBM

P. Meybohm, K. Zacharowski

9 Appendix

9.1 References

Index

Foreword

Patient Blood Management (PBM) is a compelling concept to preempt anemia, correct bleeding disorders, and minimize blood loss. This evidence-based, multidisciplinary approach does not only lead to reductions in the use of blood and blood products, and therefore to considerable cost savings, but—more importantly—it also improves patient outcomes and patient safety. Beginning with a state-wide initiative by the Department of Health in Western Australia and several hospital-based programs in the United States and Europe, PBM has evolved into a widely accepted holistic treatment concept that is a must-have for all modern health care systems.

The applicability of PBM is not limited to the perioperative setting; PBM is equally relevant to all medical fields where anemia and bleeding are prevalent and where blood and blood products are commonly administered.

After the very successful publication of this textbook in German, the editors—together with a team of internationally recognized PBM experts—have now produced an updated, expanded edition in the English language.

I am convinced that this edition will be successful in increasing awareness among clinicians and in sharing the topic with others who are interested in patient care. I hope that this new edition will help to drive the implementation of PBM until it becomes the new normal.

Denton A. Cooley, MD

Pioneering cardiovascular surgeon

Founder and Surgeon in Chief of the Texas Heart Institute

Preface

This book provides a detailed account of the modern concept of Patient Blood Management (PBM). The well-received chapters of the original German edition have been revised and expanded for the current English edition, with the additional content including a whole new section on PBM in surgical settings. In reflection of the multidisciplinary and international nature of PBM, authors from many countries with different areas of expertise were invited to contribute. We thereby succeeded in creating interfaces between the various specialist areas and meeting their demands in a better way. The well-balanced selection of authors also guaranteed an overarching and experience-based portrait of the subject matter. Each chapter is evidence-based and represents the opinions of its author(s), which were respected by the editors. Accordingly, editing was mainly restricted to formal aspects. Therefore, discrepancies may exist with regard to certain contentious questions that have not yet been corroborated through investigations, and some issues may remain unresolved.

PBM is a clinical, multidisciplinary, patient-oriented concept that focuses primarily on the treatment or avoidance of anemia, the reduction of blood loss, and the enhancement of a patient’s tolerance to anemia to improve patient safety and outcome. Only after these therapeutic options have been exhausted is the transfusion of allogeneic blood products considered. By contrast, the Optimal Blood Use project (www.optimalblooduse.eu) initiated by the European Union aims at administering the right blood product to the right patient at the right time. PBM reaches farther because it has a preventive and corrective impact on the risk factors that normally result in transfusion.

Application of the principles of PBM is indicated not only in the perioperative phase but also in all areas of medicine where treatment involves the use of blood and blood products. The primary goals of PBM are the promotion of patient safety and the improvement of patient outcomes. The concept of PBM was developed by collaboration between international experts and has been implemented in Western Australia and in several American and European centers. As early as 2010, the WHO endorsed PBM as the most important principle underlying patient safety, and the concept is featured on the website of the American Association of Blood Banks (AABB). The European Union launched its own PBM project in 2013, also with a particular focus on patient safety.

The central focus of this book—based on the recognition that there are three modifiable risk factors (blood loss, anemia, and transfusion)—is the presentation and discussion of the three pillars of PBM: avoidance, diagnosis, and treatment of preoperative anemia; reduction of peri-interventional blood loss; and augmentation of the tolerance to anemia in everyday clinical practice. Other important aspects of PBM addressed in this book include the requirements for modern transfusion medicine and surgery in the light of changing demographic trends, the procedures used for ordering blood products, the role of the preanesthesia clinic, the potential impact on the course of disease, the importance of benchmarking, and the potential financial savings and possible consequences for the public health sector.

Since the majority of investigations of PBM to date have focused on the transfusion of red blood cells, one can easily get the mistaken impression that PBM is aimed exclusively at the treatment of anemia and the transfusion of red blood cell concentrates. However, in addition to minimizing diagnostic and interventional blood loss, PBM is also targeted toward the avoidance and treatment of coagulation disorders and, as such, toward the patient-oriented administration of coagulation products and platelet concentrates.

PBM is currently undergoing rapid development and this is set to continue in the foreseeable future. Several unresolved issues—including the extent to which the treatment of anemia improves the course of disease, and the pros and cons of treatment with iron preparations and erythropoiesis-stimulating agents—are still to be clarified in prospective studies.

This book is intended as a reference for those clinicians whose patients, in addition to experiencing the consequences of their underlying disease, are often at risk for anemia, coagulation disorders, and/or major blood loss. With PBM, causal treatment is aimed at eliminating these risks, thus minimizing the side effects of autologous and allogeneic blood transfusion. Hence, PBM is one of the few concepts in modern medicine that improves patient outcomes while also saving costs.

We extend our special thanks to the authors and to the staff at Thieme Publishers, in particular Angelika-M. Findgott, Martina Habeck, Joanne Stead, and Deborah A. Cecere, who made our book on this vitally important topic possible.

Prof. Hans Gombotz, MD

Prof. Kai Zacharowski, MD, PhD, FRCA

Prof. Donat Rudolf Spahn, MD, FRCA

Contributors

Ben Clevenger, MDDepartment of AnaesthesiaDivision of Surgery and Interventional ScienceRoyal Free HospitalLondon, UK

Jochen Walter Erhard, MDProfessorEvangelische Klinik Niederrhein gGmbHDuisburg, Germany

Shannon L. FarmerSchool of SurgeryFaculty of Medicine, Dentistry, and Health SciencesUniversity of Western AustraliaCentre for Population Health Research at Curtin UniversityGlenn Forest, Western Australia, Australia

Michael Fridrik, MDLecturerCenter for Hematology and Medical OncologyInternal Medicine IIIGeneral Hospital LinzLinz, Austria

Barbara Friesenecker, MDUniversity ProfessorMedical University of InnsbruckUniversity Clinic for General and Surgical IntensiveCare MedicineInnsbruck, Austria

Gerhard Fritsch, MDSalzburg County HospitalUniversity Hospital for Anesthesiology, Perioperative Medicine and General Intensive Care MedicineSalzburg, Austria

Christof Geisen, MDInstitute for Transfusion Medicine and Immune HematologyJohann Wolfgang Goethe University HospitalGerman Red Cross Blood Donation ServiceBaden-Württemberg and HessenFrankfurt am Main, Germany

Richard S. Goldweit, MD, FACCAssistant Clinical ProfessorEnglewood Hospital and Medical CenterMount Sinai School of MedicineEnglewood, New Jersey, USA

Hans Gombotz, MDProfessorFormer Chairman of the Department of Anesthesiology and Intensive Care MedicineGeneral Hospital LinzLinz, Austria

Jeffrey Mark Hamdorf, MBBS, PhD, FRACSProfessorSchool of SurgeryUniversity of Western AustraliaCrawley, Western Australia, Australia

Michael Hiesmayr, MDUniversity ProfessorUniversity Hospital for Anesthesiology, GeneralIntensive Care Medicine, and Pain ManagementMedical University of ViennaVienna, Austria

Axel Hofmann, Dr. rer. medic., MEInstitute for AnesthesiologyUniversity of ZurichZurich, Switzerland

James Paton Isbister, MBBS, FRACP, FRCPAClinical Professor of MedicineSydney Medical SchoolSt. Leonards, New South Wales, Australia

Mazyar Javidroozi, MD, PhDDirector of Clinical ResearchDepartment of AnesthesiologyEnglewood Hospital and Medical CenterEnglewood, New Jersey, USA

Lutz Kaufner, MDDepartment of Anesthesiology – Operative Intensive Care MedicineCharité – University Medicine BerlinCampus Virchow KlinikumBerlin, Germany

Alwyn Kotze, MDConsultant Anaesthetist and Fellow NIHR CLAHRC for Leeds, York, and BradfordLeeds Teaching HospitalsLeeds, UK

Thomas Kuehlein, MDDepartment of General Medicine and Clinical ResearchHeidelberg University HospitalHeidelberg, Germany

Gerhard Lanzer, MDUniversity ProfessorMedical University of GrazUniversity Hospital for Blood Group Serology and Transfusion MedicineLKH Graz – University HospitalGraz, Austria

Jeong Jae Lee, MD, PhDProfessorDepartment of Obstetrics and GynecologySoonchunhyang University HospitalYongsan-GU, Seoul, Korea

Rudolf Mair, MDDepartment of Anesthesiology and OperativeIntensive Care MedicineGeneral Hospital Linz;Faculty of Medicine at the Kepler University of LinzLinz, Austria

Jens Meier, MDProfessor and DirectorClinic of Anesthesiology and Intensive Care MedicineFaculty of Medicine at the Kepler University of LinzLinz, Austria

Dirk Meininger, MDProfessorHospital for Anesthesiology, Operative IntensiveCare Medicine, Trauma, and Pain ManagementMain-Kinzig-ClinicsGelnhausen, Germany

Patrick Meybohm, MDAdjunct ProfessorClinic of AnesthesiologyIntensive Care Medicine and Pain TherapyJohann Wolfgang Goethe University HospitalFrankfurt am Main, Germany

Hannes Mueller, MDDepartment of Surgery IGeneral Hospital LinzLinz, Austria

Peter Rehak †Former University ProfessorMedical University of GrazUniversity Hospital for SurgeryMedical Technology and Data Processing UnitGraz, Austria

Toby RichardsSenior Lecturer in SurgeryDivision of SurgeryUniversity College LondonLondon, UK

Arno Schiferer, MDClinical Department for Cardiac, Thorax, and Vascular Surgery,Anesthesiology and Intensive Care MedicineMedical University ViennaVienna, Austria

Erhard Seifried, MDInstitute for Transfusion Medicine and Immune HematologyGerman Red Cross Blood Donation ServiceBaden-Württemberg and HessenUniversity Hospital Frankfurt am MainFrankfurt am Main, Germany

Aryeh Shander, MD, FCCM, FCCPChief, Department of Anesthesiology, Critical Care MedicineHyperbaric Medicine and Pain ManagementEnglewood Hospital and Medical CenterEnglewood, New Jersey, USA

Donat Rudolf Spahn, MD, FRCAProfessor and ChairmanInstitute of AnesthesiologySection Head MedicalAnesthesiology – Intensive Care Medicine – OR ManagementUniversity of Zurich and University Hospital ZurichZurich, Switzerland

Bruce D. Spiess, MDDepartment of AnesthesiologyVirginia Commonwealth University Medical CenterRichmond, Virginia, USA

Jost Steinhaeuser, MDUniversity of HeidelbergDepartment of General Medicine and Clinical ResearchHeidelberg, Germany

Simon Charles Bruce Towler, MD, FCICM, FANPZCA, FAMAMedical Co-Director and Intensive Care SpecialistAdjunct Professor at Edith Cowan and Curtin UniversitiesFiona Stanley HospitalMurdoch, Western Australia, Australia

Christian von Heymann, MD, DEAAProfessor Department of Anesthesiology – OperativeIntensive Care MedicineCharité – University Medicine BerlinCampus Virchow KlinikumBerlin, Germany

Philippe Van der Linden, MDProfessorDepartment of AnesthesiologyCHU Brugmann HospitalBrussels, Belgium

Christian Friedrich Weber, MDClinic of AnesthesiologyIntensive Care Medicine and Pain TherapyJohann Wolfgang Goethe University HospitalFrankfurt am Main, Germany

Alexander Weigl, MDGeneral Hospital LinzPharmacyLinz, Austria

Kai Zacharowski, MD, PhD, FRCAProfessor and ChairmanDepartment of AnesthesiologyIntensive Care Medicine and Pain TherapyUniversity Hospital FrankfurtFrankfurt am Main, Germany

Abbreviations

AABC

Australasian Association for Blood Conservation

ACSQHC

Australian Commission on Safety and Quality in Health Care

ANH

Acute normovolemic hemodilution

ARDS

Acute respiratory distress syndrome

ASA

American Society of Anesthesiologists

BSE

Bovine spongiform encephalopathy

CABG

Coronary artery bypass graft

CHD

Coronary heart disease

CHMP

Committee for Medicinal Products for Human Use

CI

Confidence interval

CJD

Creutzfeldt-Jakob disease

CPB

Cardiopulmonary bypass

CRG

Clinical Reference Group

CRP

C-reactive protein

CTR

Crossmatch-to-transfusion ratio

DAPT

Dual antiplatelet therapy

DCS

Damage control surgery

DO2

Oxygen delivery to the tissues

DRG

Diagnosis-related group

ECG

Electrocardiography

EPO

Erythropoietin

ESA

Erythropoietin-stimulating agent

FDA

Food and Drug Administration

FFP

Fresh frozen plasma

GP

General practitioner

HAA

Haematology Society of Australia and New Zealand, Australian and New Zealand Society of Blood Transfusion, and Australasian Society of Thrombosis and Haemostasis

Hb

Hemoglobin

HBOC

Hemoglobin-based oxygen carrier

HBV

Hepatitis B virus

Hct

Hematocrit

HCV

Hepatitis C virus

HES

Hydroxyethyl starch

HITS

Hospital information technology system

HLA

Human leukocyte antigens

HPA

Human platelet antigen

HR

Hazard ratio

ICCTO

International Consensus Conference on Transfusion and Outcome

ICD

International Classification of Diseases

ICU

Intensive care unit

INR

International normalized ratio

LDH

Lactate dehydrogenase

MCH

Mean corpuscular hemoglobin

MCHC

Mean corpuscular hemoglobin concentration

MCV

Mean corpuscular volume

MiECT

Minimally invasive extracorporeal circulation technology

MIS

Minimally invasive surgery

MTP

Massive transfusion protocol

NAT

Nucleic acid testing

NBA

National Blood Authority

NOAC

New oral anticoagulant

NSAID

Nonsteroidal anti-inflammatory drug

ONTraC

Ontario Transfusion Coordinators

OR

Odds ratio

PAD

Preoperative autologous blood donation

PBM

Patient Blood Management

PCC

Prothrombin complex concentrate

PCR

Polymerase chain reaction

PEG

Polyethylene glycol

PO2

Partial pressure of oxygen

PT

Prothrombin Time

RBC

Red blood cell

RCT

Randomized controlled trial

rHuEPO

Recombinant human erythropoietin

ROTEM

Rotational thrombelastometry

RPI

Reticulocyte production index

rVIIa

Recombinant activated factor VII

SABM

Society for the Advancement of Blood Management

SHOT

Serious Hazards of Transfusion

SIRS

Systemic inflammatory response syndrome

sTfR

Soluble transferrin receptor

TACO

Transfusion-associated circulatory overload

TAVR

Transcatheter aortic valve replacement

TRALI

Transfusion-related acute lung injury

TRIM

Transfusion-related immunomodulation

TTI

Total Transfusion Index

VKA

Vitamin K antagonists

VO2

Oxygen consumption

Conflicts of Interest

Shannon L. Farmer

The contributor has reported the following conflicts of interest: Shannon Farmer has received consulting/lecture honoraria or travel support from: Western Australia, Queensland, New South Wales, and South Australia Departments of Health; Australian Red Cross Blood Service; Australian National Blood Authority; Australian Jurisdictional Blood Committee; Medical Society for Blood Management; Society for the Advancement of Blood Management; Fremantle General Practice Network, Western Australia; Thieme Publishers, Stuttgart, Germany; Elsevier Science, USA; Haematology Society of Australia and New Zealand/Australian and New Zealand Society of Blood Transfusion; Novo Nordisk; Vifor Pharma; Johnson & Johnson Ethicon Biosurgery. He is Associate Investigator, Chief Investigator, and Principal Investigator of three government-sponsored research trials and a member of the Expert Panel for the European Commission Patient Blood Management Project.

Michael Fridrik

The contributor has reported the following conflict of interest: Advisory Board: Vifor Pharma.

James Paton Isbister

“I have declared no conflicts of interest. As you know there is always confusion over what is a conflict of interest. I neither presume that being Chair of the Australian Federal Government National Blood Authority Patient Blood Management can be regarded as a ‘conflict’ nor being on the Advisory Committee of the Australian Red Cross Blood Service nor Chair of a Human Research Ethics Committee. Specifically, in recent years I have not been paid honoraria for lectures or advisory roles to any company.”

Axel Hofmann

The contributor has reported the following conflicts of interest: In the past 5 years, Dr. Hofmann has received fees, honoraria, or travel support for consultancy or lecturing from the following companies and organizations: Australian Red Cross Blood Service, Brisbane, Australia; Austrian Institute of Technology, Vienna, Austria; B. Braun Melsungen, Melsungen, Germany; BioMed-zet Life Science, Linz, Austria; CSL Behring, Lisbon, Portugal; CSL Behring, Marburg, Deutschland; Fresenius Kabi, Bad Homburg, Germany; General Hospital Linz, Linz, Austria; Hospira, Leamington Spa, United Kingdom; Janssen-Cilag EMEA, Beerse, Belgium; Johnson & Johnson Ethicon Biosurgery, Somerville, NJ, USA; Johnson & Johnson Medical, North Ryde, Australia; Klinikum Sindelfingen-Böblingen, Sindelfingen, Germany; Landeskliniken-Holding, St. Pölten, Austria; Medical Society for Blood Management, Laxenburg, Austria; National Blood Authority, Canberra, Australia; Physicians World, Mannheim, Germany; Society for the Advancement of Blood Management, Richmond, VA, USA; TEM, Munich, Germany; Institute for Patient Blood Management & Bloodless Medicine and Surgery, Englewood, NJ, USA; United States Department of Health and Human Services, Washington, DC, USA; Vifor Pharma, Glattbrugg, Switzerland; Vifor Pharma Österreich, Vienna, Austria; Vifor Pharma Deutschland, Munich, Germany; Vision Plus, Monza, Italy; Western Australia Department of Health, Perth, Australia.

Mazyar Javidroozi

The contributor has reported the following conflicts of interest: Mazyar Javidroozi has been a consultant and contractor for the Society for the Advancement of Blood Management and Gauss Surgical.

Alwyn Kotze

The contributor has reported the following conflicts of interest: Alwyn Kotze has received funding related to PBM activity from the Health Foundation, an independent UK charity that aims to improve the quality of healthcare. He has also received funding for research and quality improvement unrelated to PBM from the Yorkshire and Humber Academic Health Sciences Network and the Leeds Clinical Commissioning Groups. In addition, he received expenses related to travel, accommodation, and conference attendance for one scientific conference in 2010, from Vifor Pharma.

Patrick Meybohm

The contributor has reported the following conflicts of interest: Support from Vifor Pharma, B. Braun Melsungen, CSL Behring, and Fresenius Kabi for the implementation of Frankfurt’s Patient Blood Management Program in four German university hospitals.

Hannes Mueller

The contributor has reported the following conflict of interest: Support from Nycomed Pharma for a case and photo documentation of the clinical use of TachoSil, in March 2012. Nycomed Pharma is the predecessor of Takeda Pharmaceutical Company, the current distributor of TachoSil.

Donat Rudolph Spahn

The contributor has reported the following conflicts of interest: Dr. Spahn’s academic department has received grants from the Swiss National Science Foundation, Bern, Switzerland; the Ministry of Health (Gesundheitsdirektion) of the Canton of Zurich, Switzerland for Highly Specialized Medicine; the Swiss Society of Anesthesiology and Reanimation (SGAR), Bern, Switzerland; the Swiss Foundation for Anesthesia Research, Zurich, Switzerland; Bundesprogramm Chancengleichheit, Bern, Switzerland; CSL Behring, Bern, Switzerland; and Vifor, Villars-sur-Glâne, Switzerland. Dr. Spahn was Chairman of the ABC Faculty and is Co-chairman of the ABC-Trauma Faculty, which are both managed by Physicians World Europe, Mannheim, Germany, and sponsored by unrestricted educational grants from Novo Nordisk Health Care, Zurich, Switzerland; CSL Behring, Marburg, Germany; and LFB Biomedicaments, Courtabœuf Cedex, France.

In the past 5 years, Dr. Spahn has received honoraria or travel support for consultancy or lecturing from the following companies: Abbott, Baar, Switzerland; Amgen, Munich, Germany; AstraZeneca, Zug, Switzerland; Bayer (Schweiz), Zürich, Switzerland; Baxter, Volketswil, Switzerland, and Roma, Italy; B. Braun Melsungen, Melsungen, Germany; Boehringer Ingelheim (Schweiz), Basel, Switzerland; Bristol-Myers-Squibb, Rueil-Malmaison Cedex, France, and Baar, Switzerland; CSL Behring, Hattersheim am Main, Germany, and Bern, Switzerland; Curacyte, Munich, Germany; Ethicon Biosurgery, Sommerville, NJ, USA; Fresenius, Bad Homburg, Germany; Galenica, Bern, Switzerland (including Vifor, Villars-sur-Glâne, Switzerland); GlaxoSmithKline, Hamburg, Germany; Janssen-Cilag, Baar, Switzerland; JanssenCilag EMEA, Beerse, Belgium; Merck Sharp & Dohme, Luzern, Switzerland; Novo Nordisk, Bagsværd, Denmark; Octapharma, Lachen, Switzerland; Organon, Pfäffikon/SZ, Switzerland; Oxygen Biotherapeutics, Costa Mesa, CA, USA; Photonics Healthcare, Munich, Germany; ratiopharm Arzneimittel Vertriebs-GmbH, Vienna, Austria; Roche Diagnostics International, Reinach, Switzerland; Roche Pharma (Schweiz), Reinach, Switzerland; Schering-Plough International, Kenilworth, NJ, USA; Tem International, Munich, Germany; Verum Diagnostica, Munich, Germany; Vifor Pharma Deutschland, Munich, Germany; Vifor Pharma Österreich, Vienna, Austria; Vifor (International), St. Gallen, Switzerland.

Disclaimer: “None of the above listed companies and/or entities have been directly or indirectly involved in discussing and/or developing this manuscript or parts thereof. Moreover, none of the above listed companies and/or entities have financially contributed to this endeavor in whatever form, neither directly nor indirectly. Therefore it is beyond my capacity to tell whether any of the above listed companies and/or entities do or do not have a direct financial interest in the subject matter or materials discussed in this manuscript.”

Christian Friedrich Weber

The contributor has reported the following conflicts of interest: Christian Weber has received speaker’s honoraria from CSL Behring, Roche, TEM International, and Verum Diagnostica.

Kai Zacharowski

The contributor has reported the following conflicts of interest: In the past 3 years, Professor Zacharowski has received honoraria or travel support for consultancy or lecturing from the following companies: Abbott, Aesculap Akademie, AQAI, Astellas Pharma, AstraZeneca, Aventis Pharma, B. Braun Melsungen, Baxter Deutschland, Biosyn, Biotest, Bristol-Myers Squibb, CSL Behring, Dr. F. Köhler Chemie, Dräger Medical, Essex Pharma, Fresenius Kabi, Fresenius Medical Care, Gambro Hospal, Gilead, GlaxoSmithKline, Grünenthal, Hamilton Medical, HCCM Consulting, Heinen + Löwenstein, Janssen-Cilag, med update, Medivance EU BV, MSD Sharp & Dohme, Novartis Pharma, Novo Nordisk Pharma, P. J. Dahlhausen, Pfizer Pharma, Pulsion Medical Systems, Siemens Health-care, Teflex Medical, Teva, TopMed Medizintechnik, Verathon Medical, and Vifor Pharma.

Professor Zacharowski’s academic department has received unrestricted educational grants from B. Braun Melsungen, Fresenius Kabi, CSL Behring, and Vifor Pharma.

October 2015

Chapter 1 Introduction

1.1 PBM: A Concept to Improve Patient Safety and Outcome

H. Gombotz, A. Hofmann

1.2 Requirements of Modern Transfusion Medicine

C. Geisen, M. M. Mueller, E. Seifried

1.3 Transfusion and Patient Outcomes

S. Farmer, A. Hofmann, J. Isbister

1.4 Outcomes after Platelet Transfusion

B.D. Spiess

1.5 Use of Plasma in PBM—Effectiveness and Outcomes

A. Shander, M. Javidroozi

1.6 Key Role of Benchmarking Processes in PBM

A. Hofmann, S. Farmer

1.1 PBM: A Concept to Improve Patient Safety and Outcome

H. Gombotz, A. Hofmann

1.1.1 The Triad of Anemia, Blood Loss, and Transfusion: Three Independent Risk Factors for an Adverse Outcome

Anemia. Anemia, characterized by a subnormal concentration of circulating red blood cells (RBCs), is prevalent in many different surgical populations and in critically ill patients. In patients undergoing elective surgery, the frequency of preoperative anemia ranges from 5 % to 75 %, with a higher incidence in older patients (Kulier and Gombotz 2001, Myers et al 2004, Gombotz et al 2007, Kulier et al 2007, Musallam et al 2011, Baron et al 2014). Anemia is a strong and independent predictor of adverse outcomes such as average hospital length of stay and the composite outcome of morbidity and mortality (Carson et al 1996, Nemergut et al 2007, Musallam et al 2011). One of the main contributing factors to this clinically significant condition is an absolute iron deficiency (Guralnik et al 2004). Various other factors including functional iron deficiency, chemotherapy, radiation, certain medications, menorrhagia, and congenital disorders can also cause anemia.

Perioperative blood loss. Perioperative blood loss is an independent predictor for the same adverse outcomes as those seen with anemia (Carson et al 1988, Rao et al 2005, Walsh et al 2013). Blood loss can be attributable to surgery, diagnostic or therapeutic interventions, trauma, obstetric complications, long-term anticoagulant therapy, and other reasons (Gombotz and Knotzer 2013). In nonanemic patients, acute blood loss or severe hemorrhage can lead to immediate, serious sequelae (Karkouti et al 2008b, Karkouti et al 2009, Walsh et al 2013, Hogervorst et al 2014). In patients with preexisting anemia, the tolerance to blood loss may be even lower.

Transfusion. For decades, transfusion has been considered to be the optimal treatment for anemia and/or blood loss. However, although the administration of RBCs can be lifesaving in hemodynamically unstable patients, there is little evidence of clinical benefit in hemodynamically stable patients, the group that receives the vast majority of all RBC transfusions (Bernard et al 2009, Refaai and Blumberg 2013a). Although transfusions result in corrected laboratory values, they do not treat the actual cause of anemia, nor do they stop any bleeding.

Moreover, stored blood that is transfused has limited oxygen off-loading capacity (Napolitano et al 2009). Animal models have shown that the morphological changes of RBCs during storage lead to impaired tissue perfusion followed by diminished oxygenation and inadequate removal of carbon dioxide (Tsai et al 2010, Yalcin et al 2014). These rheological changes might explain the observation of a dose–response relationship between ischemic events and RBC transfusions (Murphy et al 2007, Koch et al 2008, Lacroix et al 2015).

In addition, there is a link between transfusion and cancer recurrence. The causality is still under debate, but the findings of several clinical studies are suggestive of a causal relationship (Amato and Pescatori 2006, Al-Refaie et al 2012, Riedl et al 2013, Boehm et al 2014, Luan et al 2014, Wang et al 2014).

The relationship between transfusion-related immunomodulation (TRIM) and postoperative infection has also been the subject of scientific controversy for decades. However, in this case, the causal link has now been confirmed (Refaai and Blumberg 2013b). Retrospective and prospective observational studies in various patient populations have shown a dose–response relationship between transfusion and nosocomial infections (Lacroix et al 2007, Bernard et al 2009, Carson et al 2013, Curley et al 2014). Moreover, a meta-analysis of randomized controlled trials (RCTs) comparing the use of liberal versus restrictive transfusion thresholds showed an increase in hospital-acquired infections with liberal transfusions (Rohde et al 2014).

In preparation of the 1st International Consensus Conference on Transfusion and Outcome (ICCTO), the ICCTO research group applied the Bradford Hill criteria for establishing causation to assess the link between transfusion and adverse outcomes, using the evidence available at the time (Isbister et al 2011). The Bradford Hill criteria include strength, consistency, specificity, temporality, biological gradient or dose–response relationship (i.e., increased exposure results in increased risk), and biological plausibility of the findings. Sir Austin Bradford Hill and Sir Richard Doll used this methodology to establish the causal link between tobacco smoking and lung cancer (Darby et al 2006). When applying the Bradford Hill criteria to transfusion and adverse outcomes, the ICCTO research group found strong evidence for a causal link. Meta-analyses of RCTs and systematic literature reviews have corroborated this finding, showing that the use of liberal—as opposed to restrictive—transfusion thresholds leads to significantly higher morbidity and mortality (Carson et al 2012b) (see Chapter 1.3).

Although perceived as beneficial by many clinicians, transfusion is in fact an independent, dose-dependent, and additive risk factor for morbidity, increased hospital length of stay, and mortality in most clinical settings (Spiess 2004a, Murphy et al 2007, Bernard et al 2009, Ferraris et al 2012, Howard-Quijano et al 2013, Carson 2014, Isil et al 2015). Patients at the limits of their cardiovascular reserve, such as those undergoing cardiac surgery, may constitute an exception—they have been shown to benefit from the higher hemoglobin levels achieved with a liberal transfusion threshold (Murphy et al 2015). Overall, however, anemia, blood loss, and transfusion constitute a triad of independent risk factors for adverse outcomes (Ranucci et al 2013, Farmer et al 2013b) (Fig. 1.1).

Note

Anemia, blood loss, and transfusion constitute a triad of independent predictors of an adverse outcome.

This triad constitutes a vicious circle: blood loss and bleeding induce anemia or exacerbate preexisting anemia; anemia triggers transfusion; and transfusion—as shown in several studies—increases the risk of rebleeding, potentially leading to further blood loss (Blair et al 1986, Henriksson and Svensson 1991, Hearnshaw et al 2010, Jairath et al 2010, Restellini et al 2013, Villanueva et al 2013b). The intention of breaking this cycle by modifying the potential risk factors has led to the concept of PBM.

Fig. 1.1 Triad of independent risk factors for an adverse patient outcome. Reprinted from Farmer et al 2013b with permission from Elsevier.

1.1.2 PBM: Improving Outcomes by Preempting the Impact of the Triad

Rationale behind PBM

The rationale behind PBM is that improved patient safety and optimal clinical outcomes can be achieved when optimization and preservation of the patient’s own blood take priority over the transfusion of donor blood.

Note

To achieve an optimal clinical outcome, optimization and preservation of the patient’s own blood takes priority over the transfusion of donor blood.

This can be achieved by preempting the detrimental mechanisms within the triad: each of the three risk factors is modifiable and should be addressed as early as possible in the course of treatment. The clinical measures addressing these risks are grouped into the so-called three pillars of PBM:

1. Optimization of the patient’s endogenous RBC mass.

2. Proactive and timely bleeding management (minimization of diagnostic, interventional, and surgical blood loss).

3. Optimization of the patient’s tolerance to anemia by maximizing oxygen delivery while reducing the metabolic rate, and harnessing the patient’s ability to tolerate anemia by strictly adhering to physiological transfusion thresholds.

Note

PBM is based on three pillars. Together, they address and minimize each risk factor for an adverse patient outcome in the triad:

1. Optimization of the endogenous RBC mass through the targeted stimulation of erythropoiesis and the treatment of modifiable underlying disorders.

2. Minimization of diagnostic, interventional, and surgical blood loss to preserve the patient’s RBC mass.

3. Optimization of the patient-specific tolerance to anemia through strict adherence to physiological transfusion thresholds.

In most clinical scenarios, implementation of the first two pillars is sufficient to address all three risks in the triad. Through optimizing a patient’s RBC mass and reducing blood loss, the hemoglobin value of most patients is kept above the threshold where transfusion might be considered. However, addition of the third pillar can further reduce the transfusion rate (Meier and Gombotz 2013).

1.1.3 PBM in the Surgical and Nonsurgical Setting

The concept of PBM was initially developed in the surgical setting. By applying the three-pillar approach to the pre-, intra-, and postoperative phases, the model further evolved to the multidisciplinary, multimodal nine-field matrix shown in Fig. 1.2. Each of the fields includes a set of clinical measures that can be combined, and tailored to specific patient needs and procedures and to the expertise of a given organization.

Most PBM scenarios can be managed by a team of PBM-trained anesthesiologists, surgeons, and—in some cases—intensive care specialists. A smaller number of scenarios also require support from hematologists, gastroenterologists, radiologists, or other specialists.

Note

Each field of the multidisciplinary, multimodal nine-field matrix of PBM includes a set of clinical measures that can be combined and tailored to specific patient needs and procedures.

The principles of PBM can also be applied to procedures that have traditionally been associated with major blood loss and hemorrhage, and to medical settings where transfusion has been intrinsic to treatment. Furthermore, PBM is not confined to the transfusion of RBCs. Its principles can be expanded to preempt the transfusion of platelets, fresh frozen plasma (FFP), and other blood products that also carry risk.

Note

PBM was first developed in elective surgery but the principles can be applied in a modified form to obstetric, pediatric, and emergency surgery, trauma management, and other medical settings.

Fig. 1.2 The multidisciplinary, multimodal nine-field matrix of PBM. RBC, red blood cell. Reproduced from Hofmann et al 2007 with permission from the Department of Health, Western Australia.

1.1.4 Brief History of PBM

The renowned heart surgeon and founder of the Texas Heart Institute, Denton Cooley, was one of the first people to develop an individualized multimodal approach to blood conservation to perform complex heart surgery without the use of RBC transfusion. The positive patient outcomes associated with this approach led to the development of comprehensive hospital-wide “blood conservation programs.” One of the early programs was established at Kaleeya Hospital in Fremantle, Western Australia, in 1990. The success of this program ultimately led to the implementation of a state-wide PBM program in Western Australia (Farmer et al 2013b).

In 1994, the anesthesiologist Aryeh Shander and the clinical nurse Sherri Ozawa established a pilot program at Englewood Hospital and Medical Center in Englewood, NJ. They have reported extensively on the improved patient outcomes resulting from their programmatic approach to PBM, and their approach has become a model for numerous programs and initiatives around the world (Shander et al 2010).

The term Patient Blood Management was coined by the Australian hematologist James Isbister during a board meeting of the Medical Society for Blood Management in Prague (Farmer and Leahy 2014). He and his colleagues advocated the use of this terminology to ensure a focus on management of the patient’s own blood as opposed to the management of donor blood. In 2007, the term first appeared in the literature (Isbister 2007). In 2008, Isbister—together with colleagues from Europe—published the article “Patient blood management: the pragmatic solution for the problems with blood transfusions” (Spahn et al 2008); this was the first publication with PBM in the title. Since then, the number of PBM-related publications has been growing constantly, the articles spanning many different disciplines (Spahn et al 2008, Thomson et al 2009, Spahn 2010, Emmert et al 2011, Gombotz 2011, Ranucci et al 2011a, Gombotz 2012, Goodnough and Shander 2012, Kotze et al 2012, Meier et al 2012, Shander et al 2012a, Shander et al 2012b, Spahn et al 2012, Bruhn 2013, Farmer et al 2013b, Gombotz and Knotzer 2013, Goodnough et al 2013, Gross et al 2013, Liumbruno et al 2013, Mukhtar et al 2013, Shander et al 2013, Shaz et al 2013, Spahn et al 2013b, Cohn et al 2014, Leahy et al 2014).

The pre-, intra-, and postoperative phases of blood conservation were first described by Martyn and colleagues (2002), and the three-pillar concept of blood conservation was first mentioned in a peer-reviewed paper by Gombotz and colleagues in 2007, followed by a number of publications where this concept was referred to as the three pillars of PBM (Hofmann et al 2011). In 2008, Farmer and Hofmann combined the three phases of surgery and the three pillars of PBM to create the multidisciplinary, multimodal nine-field matrix of PBM for a PBM Program run by the Department of Health in Western Australia (Hofmann et al 2011, Hofmann et al 2012, Farmer et al 2013b). They also developed the concept of the triad of risk factors based on a review of the literature in which they identified three clinical risk factors that can be modified by PBM (Farmer et al 2013b).

The Department of Health in Western Australia was the world’s first health authority to implement PBM across the public health system of an entire state or country. Other Australian health authorities followed with similar projects, and currently PBM is being implemented nationwide with the support of leading clinicians, hospital managers, and health authorities (Spahn et al 2008, Hofmann et al 2012, Spahn et al 2012, Farmer et al 2013b).

Managed by the National Blood Authority and endorsed by the Australian National Health and Patient Research Council, five of six modules of the national Patient Blood Management Guidelines for Australia have now been developed and published online (www.blood.gov.au/pbm-guidelines). In these guidelines, the PBM Program in Western Australia is acknowledged as a pilot program that addresses many of the challenges of program implementation.

In 2010, the World Health Assembly of the WHO adopted the concept of PBM with Resolution WHA63.12: “…PBM means that before surgery every reasonable measure should be taken to optimize the patient’s own blood volume, to minimize the patient’s blood loss and to harness and optimize the patient-specific physiological tolerance to anemia following the WHO’s guide for optimal clinical use (three pillars of PBM)” (WHO 2010b).

In 2014, the European Commission announced a pilot program for the implementation of PBM in five European teaching hospitals (www.europe-pbm.eu). A number of institutions in North America, Europe, and the Asian-Pacific Region are currently establishing PBM as the standard of care. An increasing number of transfusion medicine specialists and leading professional organizations—e.g., the American Association of Blood Banks (www.aabb.org/pbm)—are supporting the concept.

1.1.5 Definition of PBM

Several descriptions and definitions of PBM have been published:

• “PBM is the timely application of evidence-based medical and surgical concepts aimed at achieving better patient outcome by relying on a patient’s own blood rather than on donor blood” (Hofmann et al 2011).

• “Evidence-based PBM is aimed at achieving better patient outcome by relying on a patient’s own blood rather than on donor blood” (Hofmann et al 2012).

• “PBM…employs a patient-specific perioperative/peri-event, multidisciplinary, multimodal team approach to managing the patient’s own blood and haemopoietic system. PBM views a patient’s own blood as a valuable and unique natural resource that should be conserved and managed appropriately” (DHWA 2011).

• “PBM improves patient outcome by improving the patient’s medical and surgical management in ways that boost and conserve the patient’s own blood” (http://blood.gov.au/patient-blood-management-pbm).

• “Patient blood management aims to improve clinical outcome by avoiding unnecessary exposure to blood components. It includes the three pillars… These principles apply in the management of any hematologic disorder. Patient blood management optimizes the use of donor blood and reduces transfusion-associated risk” (NBA 2011).

• “Professional definition: PBM is the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss in an effort to improve patient outcome” (www.sabm.org).

• “Public description: PBM is the scientific use of safe and effective medical and surgical techniques designed to prevent anemia and decrease bleeding in an effort to improve patient outcome” (www.sabm.org).

The various descriptions and definitions of PBM convey the idea that PBM

• Is evidence-based.

• Is a multimodal concept.

• Is an individualized, patient-specific therapeutic approach.

• Is multidisciplinary.

• Is applicable in surgical and nonsurgical settings.

• Improves patient outcomes.

• Improves patient safety/reduces transfusion-associated risks.

• Is based on three pillars.

• Involves the management of the patient’s own blood as opposed to management of the patient with somebody else’s (donor) blood.

In an attempt to integrate all of these aspects, the following universal definition is proposed: PBM is an evidence-based, integrated, multidisciplinary, multimodal approach to individually manage and preserve a patient’s own blood in surgical and nonsurgical settings by correcting anemia, reducing blood loss, and harnessing and optimizing the physiological tolerance to anemia, thus minimizing or avoiding transfusion and improving patient safety and outcomes.

1.1.6 The Potential Impact of PBM

In 2011, the total number of blood units collected worldwide was approximately 92 million (WHO 2011a); the number of whole blood units and RBCs transfused was probably 10 % lower (approximately 83 million). On the backdrop of this massive consumption, PBM has huge potential given the high prevalence of untreated preoperative anemia and the unmet need for bleeding management protocols—apart from protocols relating to massive bleeding (Spahn et al 2007)—and their system-wide implementation, together with a behavior-based transfusion practice that is still too liberal. Year after year, the implementation of PBM could improve the outcomes of millions of patients and help to avoid millions of allogeneic transfusions with all the associated adverse effects.

The cost of RBC transfusions to U.S. health care providers is estimated at $14 billion per annum; however, the true costs might be much higher because of transfusion-related adverse outcomes (Shander et al 2010, Hofmann et al 2013, Vamvakas 2013). A retrospective cohort study using data from the 2004 Nationwide Inpatient Sample database found that, after adjustment for confounders, the average hospital costs per patient were $17,194 higher for those who had received a transfusion than for those who had not. In terms of 2014 dollars, this would be more than $57 billion for a study population of 2.33 million inpatients who received a transfusion. A retrospective cohort study conducted in Western Australia showed that, after adjustment for potential confounders, the total hospital-associated cost of RBC transfusion reached $72 million; the study included 89,996 multiday acute-care inpatients, 4,805 of whom had received a transfusion (Trentino et al 2015).

These amounts are of macroeconomic relevance and a significant share of these costs could be reallocated, resulting in better cost-effectiveness ratios when applying PBM (Shander et al 2010).

The Austrian Benchmark Study (Gombotz et al 2007) was the first study to indicate the enormous value of PBM in elective surgery. This study showed that 97.6 %, 97.4 %, and 96.9 % of all RBC transfusions in patients undergoing total hip arthroplasty, knee arthroplasty, or coronary artery bypass (CABG) surgery, respectively, can be predicted by the following three parameters, which can all be modified through PBM (Gombotz et al 2007):

• Preoperative hemoglobin value.

• Blood loss.

• Transfusion trigger.

These results, and the fact that most transfusions are given to hemodynamically stable patients, indicate that with PBM fully implemented, RBC transfusion will become obsolete in many clinical scenarios or it will only have a minor role. PBM programs in different parts of the world have already demonstrated significant reductions in the number of transfusions with comparable or improved patient outcomes (Moskowitz et al 2010, Kotze et al 2012, Frank et al 2014b).

A number of other factors are also in favor of PBM. One is the constant threat posed by emerging and re-emerging blood pathogens, even though the problems with HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) seem to have been eliminated, albeit at an enormous cost (Goodnough et al 1999a, Goodnough et al 1999b). Besides, a shortage of allogeneic blood in high-income countries has been predicted because of a decline in blood donations, against a background of an aging population (Greinacher et al 2011). The failure to comply with existing guidelines and the broad variability in blood consumption are a drain on health budgets, in addition to presenting an increased health risk (Sanguis Study Group 1994, Gombotz et al 2007, Bennett-Guerrero et al 2010, Gombotz et al 2014). Process cost analysis has revealed that treatment with blood products is one of the most expensive forms of modern-day therapy (Shander et al 2007, Abraham and Sun 2012, Gombotz 2012).

Note

The high prevalence of untreated preoperative anemia and the unmet need for bleeding management protocols and their implementation, together with a transfusion practice that is too liberal, indicate that PBM represents a huge opportunity to improve patient outcomes and avoid millions of transfusions every year. The PBM approach is further supported by the inherent risks posed by new and re-emerging bloodborne pathogens, by blood supply pressures, and by the escalating costs associated with transfusion.

1.1.7 Clinical Practice: First Steps toward Reducing the Patient-specific Transfusion Risk

When implementing a PBM program, the identification and management of patients with a high transfusion probability can quickly yield initial results. Three principal steps can effectively achieve this aim:

• Identification of the procedures with the highest transfusion rates/indices (see Chapter 1.6). For hospitals with a patient-level database on transfusions and blood ordering processes, it should be relatively easy to capture this kind of information.

• Calculation of the mean blood loss experienced during these procedures from the hospital’s retrospective patient-level database with a representative number of cases (see Chapter 2.3). Note: the calculated perioperative blood loss takes account of the amount of blood in swabs, hematomas, etc., and is therefore more accurate than blood loss estimates.

• Calculation of the individual patient’s preoperative blood volume, based on the preoperative hemoglobin level, body weight, height, and gender. After deducting the hospital’s empirically collected, procedure-specific mean blood loss from the patient’s preoperative blood volume, the postoperative hemoglobin level can be predicted by using the Mercuriali algorithm. If the predicted hemoglobin level is close to, or below, the target hemoglobin level, PBM is clearly indicated. The target hemoglobin level or the transfusion threshold is set in accordance with the respective clinical picture and the transfusion guidelines of the pertinent societies (see Chapter 2.3).

Note

By empirically devising and calculating the mean perioperative blood loss for selected procedures, and by using patient-specific data such as the preoperative hemoglobin level, body weight, height, and gender, patients can be identified in whom PBM is indicated.

For many institutions that wish to introduce PBM, the routine correction of anemia in patients undergoing a procedure that is associated with high blood loss might be the first step toward a change in practice. With some structural adjustments, this step can be implemented almost immediately. The adaptation of treatment modalities to systematically reduce blood loss and bleeding might require more time, particularly if this involves surgical training. However, in a fully developed PBM program, anemia should be corrected always and in every patient because it is listed as a disease in the International Classification of Diseases (ICD-10), and blood loss should always be minimized. The ultimate goal is an institution-wide change in the transfusion culture (Oliver et al 2009).

1.1.8 PBM versus Optimal Blood Use—Two Different Approaches

Knowledge of the manifold nature of the problems related to transfusion has led the majority of high-income countries to formulate guidelines, and introduce hemovigilance registries and recommendations, for the optimal use of blood products; an example is the EU Optimal Use of Blood program (www.optimalblooduse.eu) (Hofmann et al 2011). These programs must not be confused with PBM, which involves the proactive and routine identification of patients with anemia and/or those at risk of clinically significant blood loss in order to provide them with a management plan aimed at reducing these risks. As a result, PBM leads to a reduction in the demand for allogeneic RBC transfusions. By contrast, the concept of optimal blood use is product-centered. It is geared toward the provision of a pathogen-free blood supply and the minimization of blood component wastage, while its clinical scope is limited to the implementation of an optimal transfusion threshold (Table 1.1).

Note

PBM reduces anemia and the demand for transfusion through improved patient care, whereas the concept of optimal blood use mainly attempts to secure the blood supply.

Conclusion

To achieve optimal clinical outcomes and improve patient safety, the management and preservation of the patient’s own blood has to take priority over the management of the patient with donor blood. This can be achieved by an evidence-based, multidisciplinary, multimodal, patient-specific treatment concept that is based on three pillars: (1) optimization of the (preoperative) endogenous RBC mass through the stimulation of erythropoiesis; (2) minimization of diagnostic, interventional, and operative blood loss to preserve the patient’s RBC mass; and (3) optimization of the patient’s physiological tolerance to anemia and strict adherence to physiological transfusion thresholds to further reduce the odds of RBC transfusion. When used in combination, these three pillars help to minimize the impact of the triad of independent risk factors for adverse outcomes (anemia, blood loss, and RBC transfusion).

The principles of PBM were first developed for elective surgery but can be applied in a modified form to obstetric, pediatric, and emergency surgery, trauma management, and medical settings. The consistent implementation of this three-pillar strategy improves the course of disease and patient safety, and leads to a substantial reduction in the use of allogeneic blood components compared with current transfusion practices.

Table 1.1 Comparison of the EU Optimal Blood Use program and the Patient Blood Management (PBM) concept (Gombotz and Knotzer 2013)

Optimal blood use

PBM

Approach

Centered on the supply of blood products

Centered on patient outcomes

Minimization of the transfusion rate

?

Yes

Optimization of the treatment regimen

No

Yes

Treatment of perioperative anemia

No

Yes

Minimization of blood loss

No

Yes

Anticoagulation management

No

Yes

Increase of anemia tolerance

No

Yes

Remuneration

Yes

No

1.2 Requirements of Modern Transfusion Medicine

C. Geisen, M. M. Mueller, E. Seifried

1.2.1 Hemotherapy—from Blood Donation to Transfusion

The quality of modern hemotherapy does not depend solely on the quality of the blood components administered. Hemotherapy must be understood as a complex process ranging from blood donation through blood testing, indication assessment, blood sampling from the recipient, and compatibility testing to transportation to the storage site and the clinical user. Within this chain, failure of the weakest link poses risks to the patient (Fig. 1.3) (Isbister 1994).

Blood Donation

Blood donors make an important voluntary and unremunerated contribution to society. Donor selection is based on medical assessment using a medical history form completed by the donor, medical interview, medical examination (at least blood pressure, pulse, temperature), and laboratory analysis (hemoglobin measurement) (e.g., Standards for Blood Banks and Transfusion Services 2014, Norfolk 2013).

Note

Only donors who meet the minimum requirements set out in national guidelines will be permitted by the physician to donate blood.

Preparation of Blood Components

Blood components. Blood transfusion in high-income countries is limited to the transfusion of blood components. RBCs, platelets, and plasma are separated from whole blood by centrifugation or collected directly from the donor through automated apheresis. Apheresis can also be used to obtain granulocytes or hematopoietic stem cells from peripheral blood.

Fig. 1.3 Hemotherapeutic chain—hemotherapy as a process. Data source: Geisen et al 2012.

Further processing. Standard blood products can be processed further, depending on the indication. This includes irradiating blood preparations to prevent transfusion-associated graft-versus-host disease, washing cellular preparations to prevent incompatibility reactions (caused by residual plasma from the donor) in sensitized individuals, and producing separated or concentrated blood components, e.g., for use in neonatology.

Note

The use of the different blood components should be based on an individualized risk–benefit analysis, corroborated by evidence from clinical trials. Specific recommendations are given in guidelines such as the United Kingdom’s Handbook of Transfusion Medicine (Norfolk 2013) and the Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives of the German Medical Association (BAEK 2011a).

Red Blood Cell Concentrates

Indication. The administration of RBC concentrates continues to be a causal therapy—with the fastest onset of efficacy—for life-threatening anemic hypoxia. The indication for transfusion must be based on strict criteria adapted to the individual patient.

Note

The clinical symptoms of anemic hypoxia determine the actual indication of RBC transfusion (physiological transfusion triggers).

However, the symptoms of anemic hypoxia are nonspecific and may be difficult to identify under clinical conditions. There are no absolute or generally valid critical transfusion thresholds that can be defined for the hemoglobin level or the hematocrit. Any decision-making regarding transfusion must take into consideration not only the laboratory values, but also the duration, severity, dynamics, and cause of anemia as well as the patient’s previous history, age, and clinical status. More detailed information on the indications for, and administration of, RBC concentrates is provided in the 2011 edition of Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives of the German Medical Association (BAEK 2011a).

Storage. RBC concentrates are stored at +4°C ±2°C for 28–49 days depending on the production process and in accordance with the manufacturer’s instructions. In recent years, there has been an extensive discussion about the extent to which the complex morphological and biochemical changes occurring during storage can affect the clinical efficacy and side effects of transfused RBC concentrates (Roback 2011). Despite a plethora of published studies, it has not yet been possible to provide definitive answers, for two reasons: first, the studies carried out were retrospective or prospective observational studies, and second, not all influencing factors were taken into account (van de Watering 2011a, van de Watering 2011b). The first RCT in this area, which addressed mortality as the primary outcome, failed to show an improved clinical outcome in premature infants transfused with fresh RBCs compared with standard blood products (Fergusson et al 2012). In a 2015 study, the transfusion of fresh RBCs, as compared with standard-issue RBCs, did not decrease the 90-day mortality among critically ill adults (Lacroix et al 2015). Several other large RCTs assessing the effect of RBC storage time on mortality or multiple organ dysfunction are currently in progress and may help to shed more light on the influence of storage time (Flegel et al 2014).

Note

The question as to whether there is a causal link between the shelf life of RBC concentrates and the occurrence of adverse reactions can ultimately only be resolved by prospective randomized clinical trials.

Platelet Concentrates

Platelet concentrates contain more than 2 × 1011 platelets. Their volume is between 200 mL and 350 mL. The platelets are resuspended in either plasma or an additive solution. They are stored at +22°C ±2°C under continuous agitation.

Product types. Platelet concentrates are isolated either from whole blood donations through pooling of four buffy coats from donors with the same AB0 and Rhesus D group, or through platelet apheresis from a single donor (Schrezenmeier and Seifried 2010).

Note

In nonrefractory recipients, pooled platelet concentrates and apheresis platelet concentrates are comparable in terms of safety, tolerability, and efficacy (Table 1.2) (Schrezenmeier and Seifried 2010, BAEK 2011a).

For supply reasons, both product types should be available. That way, products from donors compatible for human leukocyte antigen (HLA) and/or human platelet antigen (HPA) can be promptly administered to immunized recipients, while keeping available a supply of platelet concentrates with special characteristics.

Indication. Thresholds for the therapeutic administration of platelet concentrates and for their prophylactic administration before procedures and interventions are provided in the 2011 edition of the Cross-Sectional Guidelines of the German Medical Association (BAEK 2011a).

Therapeutic Plasma

Various types of therapeutic plasma are available for clinical use. The efficacy of the various product types—FFP, methylene-blue-/light-treated plasma, lyophilized human plasma, and pooled solvent/detergent-treated plasma—is broadly similar. Plasma is transfused in an AB0-compatible fashion (BAEK 2011a).

Indication. Plasma is used for the replacement of deficient coagulation factors (provided the missing factors are not available as factor concentrates) and for plasma exchange therapy. The specific indications have been narrowed in recent years (Shepard and Bukowski 1987, Bell et al 1991, Rock et al 1991) and are available in the 2011 edition of the Cross-Sectional Guidelines of the German Medical Association (BAEK 2011a) (see also Chapter 1.5).

1.2.2 Quality Assurance in Clinical Hemotherapy

Blood Donation Centers

Institutions that collect blood and blood components, produce blood products, and/or store and supply them, are legally required to have an effective quality assurance system in place that meets stringent safety and utility requirements.

Health Care Centers

In many countries, inpatient and outpatient centers that administer blood products are also required to set up a quality assurance system. Quality assurance comprises the entire spectrum of staffing, organizational, technical, and normative measures designed to maximize the quality of patient care and to improve it in line with the state of the art in medical science. In hemotherapy, quality indicators for the analysis and use of blood products must be defined. In addition, the qualifications and duties of the responsible persons must be defined. The quality assurance measures and operating procedures must be summarized in a quality management manual.

1.2.3 Safety of Blood Products—Adverse Reactions

Classification. Based on their pathophysiological mechanisms, any adverse reactions associated with the use of blood products can generally be classified as immune-mediated or nonimmune-mediated transfusion reactions or as transfusion-related infections (Table 1.3). Another classification system is based on the time course; it distinguishes between acute side effects, e.g., immediate-type hemolytic reactions, and delayed side effects, e.g., delayed-type hemolytic reactions (Table 1.3). The International Haemovigilance Network provides useful definitions of adverse reactions on its website (www.ihn-org.com).

Mandatory notification. Serious transfusion reactions must be reported to the manufacturer of the blood product and to the respective competent authority. Examples of reports in which the reported data are evaluated include the United Kingdom’s Serious Hazards of Transfusion (SHOT) report (Bolton-Maggs et al 2013) and the annual hemovigilance report by the Paul Ehrlich Institute in Germany (Funk et al 2012a).

Incidence.