Manual of Veterinary Transfusion Medicine and Blood Banking

Using a practical approach, the Manual of Veterinary Transfusion Medicine and Blood Banking provides veterinary practitioners with evidence-based guidelines to refer to at the clinical practice level.

• Provides evidence-based information on transfusion medicine and blood banking practices
• Presents sections on recipient screening, donor selection, blood collection and storage, and how to meet blood product demands
• Includes useful protocols for transfusions and blood banking relevant to clinical practice
• Incorporates the balanced perspectives of veterinarians and veterinary technicians
• Contains information pertaining to large, small, and exotic animals

• Language: English
• Publisher: Wiley
• Release date: Jul 7, 2016
• ISBN: 9781118933046

Book preview

Contributors

Anthony C.G. Abrams-Ogg, DVM, DVSc, DACVIM (SAIM)

Professor

Department of Clinical Studies

Ontario Veterinary College

University of Guelph Guelph, Ontario, Canada

Sophie Adamantos, BVSc, CertVA, DACVECC, DECVECC, MRCVS, FHEA

Clinician in Emergency and Critical Care

Small Animal Hospital

Langford Veterinary Services

University of Bristol Langford, North Somerset, UK

Brandee L. Bean, CVT, VTS (ECC)

Adobe Animal Hospital

Los Altos, California, USA

Shauna L. Blois, DVM, DVSc, DACVIM

Assistant Professor

Department of Clinical Studies

Ontario Veterinary College

University of Guelph Guelph, Ontario, Canada

Manuel Boller, Dr. Med. Vet., MTR, DACVECC

Senior Lecturer

U-Vet Werribee Animal Hospital

Faculty of Veterinary and Agricultural Sciences

University of Melbourne Werribee, Victoria, Australia

Marjory Brooks, DVM, DACVIM

Director, Comparative Coagulation Section

Department of Population Medicine and Diagnostic Sciences

College of Veterinary Medicine

Cornell University Ithaca, New York, USA

Mary Beth Callan, VMD, DACVIM

Professor of Medicine

Department of Clinical Studies – Philadelphia

School of Veterinary Medicine

University of Pennsylvania Philadelphia, Pennsylvania, USA

Stephen Cital, RVT, SRA, RLAT

Director of Anesthetic Nursing and Training, United Veterinary Specialty and Emergency

Veterinary Technician, San Francisco Zoo

San Jose, California, USA

Angela Colagross-Schouten, DVM, MPVM, DACLAM

Senior Veterinarian

California National Primate Research Center

Davis, California, USA

Brent C. Credille, DVM, PhD, DACVIM

Assistant Professor, Food Animal Health and Management Program

Department of Population Health

College of Veterinary Medicine

University of Georgia Athens, Georgia, USA

Thomas K. Day, DVM, MS, DACVA, DACVECC

Emergency and Critical Care Specialist, Anesthesiologist

Veterinary Emergency Service/Veterinary Specialty Center

Middleton, Wisconsin, USA

Kira L. Epstein, DVM, DACVS, DACVECC

Clinical Associate Professor Department of Large Animal Medicine College of Veterinary Medicine University of Georgia Athens, Georgia, USA

Andrea Goodnight, DVM

Veterinarian, Oakland Zoo

Associate Veterinarian, CuriOdyssey Science and Wildlife Center Oakland, California, USA

Marie K. Holowaychuk, DVM, DACVECC

Critical Care Vet Consulting Calgary, Alberta, Canada

Karen Humm, MA, VetMB, CertVA, DACVECC, DECVECC, FHEA, MRCVS

Lecturer in Emergency & Critical Care

Royal Veterinary College

Queen Mother Hospital for Animals

Hatfield, Hertfordshire, UK

Caroline Kisielewicz, MVB, CertSAM, DECVIM-CA

Chestergates Veterinary Specialists

Chester, Cheshire, UK

Angela M. Lennox, DVM, DABVP (Avian & Exotic Companion Mammal), DECZM (Small Mammals)

Senior Veterinarian, Avian and Exotic Animal Clinic of Indianapolis

Section Editor, Journal of Exotic Pet Medicine AEMV Indianapolis, Indiana, USA

Sally Lester, DVM, MVSc, DACVP (Clinical and Anatomic)

Laboratory Director

Pilchuck Veterinary Hospital

Seattle Veterinary Specialists Seattle, Washington, USA

Cheryl L. Mansell, BMLS, DipVN

Australian Red Cross Blood Service

Melbourne, Victoria, Australia

Kimberly Marryott, CVT

Manager, Penn Animal Blood Bank

Matthew J. Ryan Veterinary Hospital

University of Pennsylvania Philadelphia, Pennsylvania, USA

Margaret C. Mudge, VMD, DACVS, DACVECC

Associate Professor

The Ohio State University

Department of Veterinary Clinical Sciences Columbus, Ohio, USA

Jody Nugent-Deal, RVT, VTS (Anesthesia/Analgesia) (CP - Exotics)

Small Animal Anesthesia, Surgery and Neurology Supervisor

University of California Davis William R. Pritchard Veterinary Medical Teaching Hospital Davis, California, USA

Rebecca J. Nusbaum, CVT, VTS (ECC)

HemoSolutions

Colorado Springs, Colorado, USA

Kristina Palmer, RVT, VTS (CP - Exotics)

Companion Avian and Exotic Animal Medicine Supervisor

William R. Pritchard Veterinary Medical Teaching Hospital

University of California Davis Davis, California, USA

Charlotte Russo, FdSc RVN, Dip AVN

Blood Transfusion Nurse

Royal Veterinary College

Queen Mother Hospital for Animals Hatfield, Hertfordshire, UK

Caroline Smith (Hirst), BVetMed, MVetMed, DACVECC, DECVECC, MRCVS

Clinician in Emergency and Critical Care

Small Animal Hospital

Langford Veterinary Services

University of Bristol Langford, North Somerset, UK

Nicole Spurlock, DVM, DACVECC

Small Animal Specialist Hospital

North Ryde, New South Wales, Australia

Laura Summers, DVM, DACLAM

Faculty Veterinarian

Carrington College

Stockton, California, USA

Robyn K. Taylor, RVN

Critical Care and Transfusion Nurse

The Royal Veterinary College

North Mymms, Hertfordshire, UK

Lynel J. Tocci, DVM, DACVECC, MT(ASCP)SBB

Department of Emergency and Critical Care

Lauderdale Veterinary Specialists

Fort Lauderdale, Florida, USA

Julie M. Walker, DVM, DACVECC

Clinical Assistant Professor

Department of Medical Sciences

School of Veterinary Medicine

University of Wisconsin Madison, Wisconsin, USA

K. Jane Wardrop, DVM, MS, DACVP

Professor

Department of Veterinary Clinical Sciences

College of Veterinary Medicine

Washington State University Pullman, Washington, USA

Olivia H. Williams, RVT

Piedmont Equine Associates

Madison, Georgia, USA

Kenichiro Yagi, BS, RVT, VTS (ECC, SAIM)

ICU Manager/Blood Bank Manager, Adobe Animal Hospital

Instructor, Department of Veterinary Technology, Foothill College Los Altos, California, USA

About the Editors

Kenichiro Yagi, BS, RVT, VTS (ECC, SAIM)

Kenichiro Yagi is a veterinary technician practicing at Adobe Animal Hospital in Los Altos, California as an ICU and Blood Bank Manager. He has established and operates a veterinary blood bank with a sustained blood donor program and the ability to process blood components. He is an active educator lecturing internationally and providing practical instruction on site and online, having written textbook chapters and numerous articles on topics including veterinary transfusion medicine, blood banking, respiratory care, and critical care nursing. He has contributed to the progression of the veterinary technician profession and emergency and critical care through his service as a board member for the Veterinary Emergency Critical Care Society as well as the Academy of Veterinary Emergency and Critical Care Technicians, and as the State Representative Committee Chairperson of the National Association of Veterinary Technicians of America. He is also pursuing a graduate degree in Biomedical Sciences with an emphasis in veterinary medicine and surgery through the University of Missouri. Ken invites everyone to ask Why? to understand the What and How of our field, and to constantly pursue new limits as veterinary professionals.

Marie K. Holowaychuk, DVM, DACVECC

Dr. Marie Holowaychuk is a specialist in emergency and critical care, and is an accomplished speaker, consultant, researcher, and locum living in Calgary, Alberta, Canada. She grew up in Edmonton, Alberta and after two years of pre-veterinary medicine at the University of Alberta, she entered veterinary school at the Western College of Veterinary Medicine at the University of Saskatchewan. She received her Doctor of Veterinary Medicine in 2004 and then completed a yearlong rotating internship in small animal medicine and surgery at Washington State University. Thereafter, she completed a three-year small animal emergency and critical care residency at North Carolina State University. After becoming board certified in 2008, she was Assistant Professor of Emergency and Critical Care Medicine at the Ontario Veterinary College for five years until she moved home to Alberta. Dr. Holowaychuk has been primary or co-author of over 25 manuscripts published in peer-reviewed journals and is also an Assistant Editor for the Journal of Veterinary Emergency and Critical Care.

Preface

The practice of transfusion medicine and blood banking has grown enormously during the past decade and this has created a demand for a comprehensive guide to the discipline. There are hundreds of publications in the veterinary literature pertaining to this subject area, with new studies being made available each month. Despite the rapidly increasing amount of information available, a textbook dedicated to this topic has not previously been published. While there are chapters in textbooks dedicated to the practice of transfusion medicine or blood banking, no references focus solely on this important subject area. Likewise, resources usually pertain to dogs and cats, with little information applicable to food animals, horses, or exotic pets.

We recognized the need to fill the gap and communicate best practices by providing a manual of veterinary transfusion medicine and blood banking. Both of us have a strong interest in transfusion medicine, as well as clinical and research experience with blood banking. We eagerly accepted the challenge of providing an evidence-based resource that brings information regarding all species and aspects of transfusion medicine and blood banking together in one place. We compiled this textbook with the goal of providing a resource that would be helpful for veterinary professionals working in academic, referral, or general practice, as well as technicians and residents preparing for specialty certification exams. Whenever possible, authors used recent peer-reviewed veterinary (and sometimes human) journal articles and supplemented with other resources or anecdotal experience when peer-reviewed information was lacking. Overall, we feel the result is a practical and thorough presentation of the current knowledge of veterinary transfusion medicine and blood banking.

We are also aware that the disciplines of transfusion medicine and blood banking are very reliant on a veterinarian-technician team. As such, we proudly co-edited this textbook as aveterinarian and technician team. Similarly, many of our chapters are co-written by a veterinarian and technician. We both personally learned a great deal from these different perspectives and feel that this insight from all members of the group that would be participating in blood banking or transfusion administration within the hospital is beneficial. This textbook contains evidence-based descriptions of theory and practical step-by-step procedures pertaining to blood products, blood product administration, blood banking, and meeting blood product demands. While most of these sections pertain to small animals, additional chapters focus on large animals and exotic pets in the section on transfusion medicine in other species.

Probably the most challenging aspect of writing this textbook was staying current with all of the literature in the field of veterinary transfusion medicine and blood banking during the editing process. We finally had to forego our concern that we would miss the opportunity to include groundbreaking research and submit the content for publication. In the meantime, we found ourselves adding new publications right up until the point of submission. Even so, we recognize that knowledge gaps exist, and the most up-to-date information will still come from the most recently published literature and that new and exciting research will need to be included in future editions of the textbook. We welcome any suggestions, ideas, or corrections that should be incorporated into new editions that we look forward to providing in the not-too-distant future.

We would like to thank the Wiley-Blackwell editorial team for responding to our endless emails and supporting us throughout this endeavor. We also gratefully acknowledge our authors without whose contributions this textbook would not have been possible.

Marie K. Holowaychuk and Kenichiro Yagi

Section I

Introduction to Veterinary Transfusion Medicine

Chapter 1

Evolution of Veterinary Transfusion Medicine and Blood Banking

Marie K. Holowaychuk¹ and Kenichiro Yagi²

¹Critical Care Vet Consulting, Calgary, Alberta, Canada

²Adobe Animal Hospital, Los Altos, California, USA

Introduction

From ancient times to the modern day, knowledge of transfusion medicine and blood banking has advanced from blood existing as a spiritual fluid of vitality to it being a lifesaving therapeutic resource used on a regular basis. The most significant advancements in transfusion medicine have been made during the past 200 years, with veterinary transfusion medicine becoming a specialized area of interest for the past few decades. Transfusion medicine has progressed from fresh whole blood transfusions to targeted component therapy, with veterinary professionals performing transfusions in small, large, and exotic animals. Providing a safe and reliable blood product with availability that meets demands is now an emerging focus, as new knowledge cautions practitioners that transfusions, even when properly administered, can be harmful to patients.

Advancements in veterinary transfusion medicine include blood typing, compatibility testing, laboratory diagnostics to determine whether a transfusion is indicated, proper administration and dosage of blood products, as well as prevention, monitoring, and treatment of transfusion-associated complications. Veterinary blood banking has progressed from whole blood collection on an emergency basis with minimal regard to pre-transfusion compatibility testing, to the collection, storage, and processing of blood components and transfusion only after suitable recipient screening. This has led to the establishment of commercial blood banks and processing of blood products using specialized equipment, with evidence-based guidelines regarding donor screening. Additional advancements include methods to maximize the limited donor pool and awareness of storage lesions, as well as safety measures such as leukoreduction. Professional organizations such as the Veterinary Emergency and Critical Care Society (VECCS), American College of Veterinary Emergency and Critical Care (ACVECC), American College of Veterinary Internal Medicine (ACVIM), and American College of Veterinary Anesthesia and Analgesia (ACVAA), among others, actively pursue advancement of knowledge in the field of veterinary transfusion medicine and blood banking. Veterinary transfusion medicine as a specialty area of knowledge is growing, as seen through the re-emergence of efforts to establish sustainable organizations such as the International Association of Veterinary Blood Banks (IAVBB), the Association of Veterinary Hematology and Transfusion (AVHTM), and the proposed Academy of Veterinary Transfusion Medicine Technicians (AVTMT). Veterinary transfusion medicine is a discipline in its own right and will continue to play a vital role in veterinary medicine in an effort to improve patient care.

History of transfusion medicine

Ancient knowledge

Early practices and customs relating to the blood of ancient days include people drinking the blood of fallen gladiators to gain strength, religious figures attempting to heal themselves by drinking blood from the youth, and doctors inducing hemorrhage to let out bad blood due to the belief that blood was one of the four fundamental humors of Hippocratic medicine and blood-letting would bring balance to the humors and restore health (Greenwalt 1997). Early practices were often influenced by religion and superstition, as well as innate emotions and fears elicited by the sight of blood. People believed blood was the key to vitality, even though the discovery and description of the circulatory system did not occur until the 17th century.

Early concepts

It is unclear who first conceived the idea of blood transfusions. Hieronymus Cardanus (1505–1576) is given credit in some literature, while Magnus Pegelius obtained the right to publish on the topic under Emperor Rodolphus II's rule in 1593. Andreas Libavius was the first person clearly documented in history to advocate for blood transfusions; he recorded his thoughts on using a silver tube to connect the arteries of two individuals to allow blood from the young man to pour into the artery of the old man. However, there is no evidence indicating that transfusions were performed by Libavius (Greenwalt 1997).

Following William Harvey's description of the circulatory system, Francesco Folli of Florence published the first book on transfusions stating that transfusions could be used to treat illness and rejuvenate aged men. However, Folli stated in the book that that he had never performed a transfusion with the apparatus that he described was needed for the procedure (Greenwalt 1997).

First animal-to-animal transfusion

Richard Lower (1631–1691) performed the first successful animal-to-animal transfusion in February 1665; previous to this he had years of failed attempts due to clotting in the tubes (Figure 1.1). Lower used a medium-sized dog and exsanguinated it until its strength was nearly gone, and then connected the cervical arteries of two large mastiffs to the jugular vein of the exsanguinated dog. The recipient in the experiment was apparently oblivious to its hurts and soon began to fondle its master and to roll on the grass to clean itself of blood, indicating his first successful attempt to use a blood transfusion as a form of resuscitation. While Lower's report was published in 1666, Jean-Baptiste Denis (1635–1704) also claimed to have performed the first successful animal-to-animal transfusion; unfortunately, his report was delayed from publication for a year due to the imprisonment of the editor of the publication (Greenwalt 1997).

c01f001

Figure 1.1 A portrait of Richard Lower, a physician who performed the first reported animal-to-animal transfusion. (Public domain.)

First animal-to-human transfusions

While similar uncertain claims to the first human transfusion have been made, Jean-Baptiste Denis is believed to have performed the first animal-to-human transfusions. He performed a transfusion of lamb blood to a 15-year-old child who was suffering from a persistent fever; the child was reported to have a clear and smiling countenance after the transfusion. Denis also performed a transfusion to the son of the Prime Minister of Sweden (Baron Bond), without successfully curing him, and to others without complications (Greenwalt 1997).

Lower, who had performed the first animal-to-animal transfusion, also performed an animal-to-human transfusion in 1667 to Arthur Coga, who was described as a harmless lunatic and eccentric scholar at Pembroke College. He received a transfusion from the artery of a sheep and was reported to have found himself well afterwards.

The most notable report of an animal-to-human transfusion was on 19 December 1667, when Denis treated a patient named Antoine Mauroy, a 34-year-old newlywed husband who ran away to Paris to spend time indulging in sensual pleasures (Figure 1.2). Denis thought that a transfusion of calf blood would help calm Mauroy's urges due to the gentle nature of calves. The transfusion was reported to improve Mauroy's issues, making him quieter. The procedure was repeated several days later, but that time Mauroy experienced burning in his arm, pain over his kidneys, and tightness in his chest. A day later, he exhibited bleeding from his nose and dark urine. This signifies the first report of a severe transfusion reaction, likely acute hemolysis. Mauroy's wife insisted that Mauroy be treated a third time 2 months later when he was exhibiting similar behavior, but Mauroy did not comply. He died the following night without receiving the transfusion. Mauroy's wife was bribed by Denis' enemies to state that a transfusion killed her husband, leading to Denis' trial for manslaughter, for which he was exonerated. Rumors suggest that Mauroy's wife poisoned him with arsenic, although the truth is unknown (Farr 1980).

c01f002

Figure 1.2 A depiction of an animal-to-human transfusion performed in the 1600s. (Wellcome Library, London. Boutesteyn Leyden 1692. Creative Commons.)

Because of Denis' experiences in France, his enemies were able to instate the Edict of Châtelet, effectively banning transfusion practices in France. It is likely that the magistrates in Rome and the Royal Society also enacted similar bans, therefore while some experimental transfusions were performed in other parts of the world, advancements in transfusion medicine were halted for the next 150 years (Greenwalt 1997).

18th and 19th centuries

During the 18th century, the value of transfusions in patients with severe wounds and hemorrhage was revealed. In 1749, a member of the Faculty of Paris named Cantwell stated that transfusions should not be forbidden in desperate situations. In 1788, Michele Rosa published is findings that animals in severe shock required whole blood instead of serum for successful resuscitation.

During the 19th century, James Blundell (1790–1877), who had witnessed many women die from postpartum hemorrhage, performed experiments with animals in preparation for transfusions to his patients (Figure 1.3). He limited his patients receiving transfusions to those suffering from severe hemorrhage and applied the knowledge gained by John Leacock on the apparent harm of xenotransfusions (transfusion of blood from a different species), thus attempting human-to-human transfusions. While the archives are somewhat contradictory regarding the number of successful cases, records show that in 1829 Blundell was able to successfully save a 25-year-old woman with postpartum hemorrhage by transfusing blood from one of the surgical team members. The blood transfusion was performed with a brass syringe, although Blundell later developed an instrument called the impellor, a funnel-like apparatus that was used well into the late 19th century (Figure 1.4). While Blundell voiced his opinion against the transfusion of animal blood to human patients, the practice remained prevalent as transfusion therapy returned to medical practice. However, reports of transfusions were rare, likely due to the fact that blood clotting was a common limitation in performing transfusions (Greenwalt 1997).

c01f003

Figure 1.3 A portrait of James Blundell, a physician who performed the first reported human-to-human transfusion. (Public domain: The National Portrait Gallery, Volume II, 1820.)

c01f004

Figure 1.4 A section of the impellor device developed by James Blundell for blood transfusions. (Wellcome Library, London. Creative Commons.)

Blood groups discovered

In the late 1800s there was significant work done by various physicians to study the effects of transfusions between different species. In 1874, Ponfick presented his findings of residues from lysed red blood cells (RBCs) in a patient who died after receiving a transfusion from a sheep. Ponfick also observed detrimental physical effects including respiratory distress, defecation, and convulsions, as well as post-mortem findings such as dilated hearts, pulmonary and serosal hemorrhage, enlarged and congested kidneys, and hemorrhage of the liver in dogs, cats, and rabbits receiving sheep blood. Ponfick also described the accumulation of hematin in the renal tubules of surviving animals that developed kidney insufficiency. Ponfick's findings were consistent with Panum, Landois, and Euhlenberg's findings suggesting that adverse outcomes could be seen with transfusions between different species, secondary to hemolysis, kidney injury, and hyperkalemia (Greenwalt 1997).

In the 1800s, human-to-human transfusions were performed with a reasonable degree of success, frequently without signs of adverse reactions. This is probably because ABO incompatibilities in the general Caucasian population were only anticipated in one-third (35.6%) of randomly paired individuals (Greenwalt 1997). Nevertheless, there were still significant numbers of human-to-human transfusions resulting in fatal complications, which could not be explained by the work of Ponfick and others investigating inter-species transfusions (Greenwalt 1997). It was not until Landsteiner demonstrated agglutination using the serum from healthy humans mixed with another human's blood that the concept of blood groups (A, AB, B, and O) was established, which led to advancements in compatibility testing using assessments for agglutination (Landsteiner 1961). In 1910, von Dungern and Hirszfeld published a report on the inherited nature of blood groups; the practice of exclusively using O donors for transfusions began in the 1930s (Greenwalt 1997).

Advent of anticoagulation

The impellor was the tool designed by Blundell and used for transfusions until the 20th century. Another cannula device was devised by Crile in an effort to prevent blood clotting; it enabled the temporary joining of the recipient's vein and donor's artery, although it took significant surgical skill and strong donor will to accomplish this procedure. Other methods of transfusion included using paraffin to line the blood collection container, defibrinating the blood, and transfusing the non-clotted portion of blood (Greenwalt 1997).

Various anticoagulants were also studied in an effort to make the transfusion process more feasible, including the use of sodium phosphate by the well-known Braxton-Hicks, but none of his four patients receiving transfusions survived. Ammonium sulfate, sodium bicarbonate, sulfarsenol, ammonium oxalate, arsphenamine, sodium iodide, sodium sulfate, and hirudin (extracted from leeches) were all anticoagulant compounds investigated and reported by various physicians in the 19th and 20th centuries. In 1890, Nicolas Maurice Arthus reported that sodium citrate was able to permanently keep blood in liquid form, but it was not until 1915 that the invention of sodium citrate for blood transfusion was officially claimed. In 1955, Lewisohn was awarded the American Association of Blood Banks (AABB) Landsteiner Award for producing the first sodium citrate solution in a vial. Citrate was initially blamed as a cause of febrile non-hemolytic transfusion reactions, which were later determined to be the result of endotoxin from bacterial contamination (Greenwalt 1997).

Concept of blood banking

While blood mixed solely with 3.8% sodium citrate exhibited hemolysis after 1 week of storage, a mixture of blood, sodium citrate, and dextrose did not demonstrate hemolysis for 4 weeks. During World War I, Oswald H. Robertson established the first blood bank at the United States Army Base Hospital No.5 by using collection sets that were autoclaved and designed to collect up to 800 mL of blood into 160 mL of 3.8% sodium citrate. In 1937, an article written by Bernard Fantus at the Cook County Hospital in Chicago describes collecting 500 mL of blood into 70 mL of 2.5% sodium citrate into a chilled flask, then storing it under refrigeration at 4–6 °C. This became known as the first blood bank, which stored blood for 4–5 days (McCullough 2012).

While dextrose solutions were known to increase the storage time of RBCs, maintaining sterility was still an issue due to caramelizing of the dextrose solution during autoclaving of the collection system. In the 1940s, acid-citrate dextrose (ACD) solutions were developed; the addition of acidic forms of sodium citrate prevented caramelization, which allowed extension of storage of RBC products to 21 days (Greenwalt 1997).

As the potential storage time for RBCs increased, concerns regarding RBC metabolism during storage arose. It was already recognized that 2,3-diphosphoglycerate (2,3-DPG) was a substance present in RBCs, even though its role in oxygen binding was not yet elucidated. The level of 2,3-DPG was also observed to be lower in more acidic environments, leading to the development of citrate-phosphate-dextrose (CPD) solutions in 1947. These solutions raised the pH to 5.6 and the addition of phosphate resulted in better preservation of 2,3-DPG. By 1960, the introduction of additive solutions containing adenine increased the storage time (Nakao et al. 1960) and the RBC survival time was extended to 42 days (Simon et al. 1962). This vastly improved the ability to store RBCs instead of using fresh whole blood.

Plasma component use

The introduction of plasma component therapy occurred during World War II, mainly for the treatment of shock. Edwin J. Cohn and his colleagues developed the method of fractionation, thus enabling the use of human albumin and plasma as resuscitation fluids. Cohn's methods continue to be used today, with some modifications (Greenwalt 1997).

Invention of plastic bags and component processing

The patent for plastic containers for blood component therapy was filed by Carl Walter in 1950, which led to the development of component separation and transfusions that otherwise would not have been possible. The American Red Cross Blood Program experienced an increase in the use of packed red blood cells (PRBCs) from 0.8% to 88% of reported transfusions between 1967 and 1978 with the implementation of multi-chambered plastic bags connected by tubing (Greenwalt 1997). Baxter Corporation commercialized the invention with the Fenwal division (named partly after Walter), which later became its own company. The ability to separate plasma from RBCs led to the abundant supply of plasma and production of plasma protein concentrates, as well as the ability to produce platelet concentrates.

Plasma protein concentrates

In 1965, Judith Pool discovered that fresh frozen plasma (FFP) thawed at refrigeration temperatures would allow coagulation factor VIII to remain precipitated, leading to the administration of high concentrations of factor VIII to hemophilia patients during cryoprecipitate transfusions (Pool and Shannon 1965). In addition, Edwin Cohn developed the technique of creating factor VIII concentrates through fractionation, allowing for home storage of factor VIII in refrigerators and self-administration of factor VIII by hemophilia patients.

Platelets

The advent of multi-chambered plastic bags allowed for the separation of platelets into concentrates. The National Cancer Institute played a major role in investigating the use of platelet concentrates for the treatment of thrombocytopenia during the 1960s (McCullough 2012). Methods of preparing platelet concentrates and performing transfusions were established and reduced mortality rates in oncology patients with thrombocytopenia. The lifespan of platelet concentrates was initially a limitation as they were only viable for several hours, although Murphy and Garner established that they could be stored for several days at room temperature, which vastly improved the ability of platelets to be used as a transfusion product (Murphy and Gardner 1969).

Apheresis

Jack Latham developed the concept of separating blood components and selectively extracting the portions necessary for treatment, and established a semi-automated system for plasmapheresis (McCullough 2003). More recent improvements have allowed the separation and extraction of platelets, as well as leukocytes. Plasmapheresis is currently being investigated for its ability to remove antibodies and toxins (Crump and Seshadri 2009; Khorzad et al. 2011; Nakamura et al. 2012). Plateletpheresis continues to be a method of collection for platelet concentrates.

Leukoreduction

As fractionation of components into RBCs, platelets, and plasma became more common, the white blood cells (WBCs) that remained were considered residual in nature. WBCs cause febrile non-hemolytic reactions, transfusion-related immunomodulation, and can aid the transmission of specific viruses (Zimring et al. 2009). In the 1980s, methods of filtration by passing collected blood through a membrane were developed and termed filter leukoreduction. This method is used in the majority of human blood banks today to reduce transfusion-related complications. Development of apheresis also led to the harvesting of components that do not contain leukocytes and is termed process leukoreduction (Zimring 2009).

The veterinary field

While the first experimental animal-to-animal transfusion was performed prior to transfusions between animals and humans, the development of veterinary transfusion medicine and blood banking is relatively recent. The first commercial veterinary blood banks were established in the late 1980s and more blood banks exist now than ever before. Many of the same concepts found in human transfusion medicine are employed in the veterinary field, with progressively larger numbers of veterinary studies being performed and findings presented to refine the practice of veterinary transfusion medicine.

Current veterinary transfusion and blood banking practices

Despite how common the practice of administering blood products has become in veterinary clinics worldwide, there is a remarkable lack of information regarding the transfusion practices used. While studies have been published documenting transfusion-related complications such as transfusion reactions, organ injury, or coagulopathies, little has been described in the literature as to how veterinary professionals are actually administering blood products or taking steps to ameliorate the consequences of transfusions. Comparatively, even less information is available describing the current use of veterinary blood donors. The little veterinary information published in this regard is in the form of surveys. While these surveys have selection bias and do not represent the views of the entire veterinary field, they function to provide some insight as to current veterinary transfusion practices.

Surveys on veterinary transfusion medicine and blood banking

The first survey documenting transfusion practices was published more than 20 years ago and included responses from 25 small animal clinics geographically stratified across the United States. It was a telephone survey that asked questions to exclusively small animal practices performing at least six canine blood transfusions per year. The survey responses revealed that the primary source of donor blood was from a borrowed dog at 48% of practices, an in-house dog kept on the premises at 48% of practices, and a nearby veterinary school at one practice. Two-thirds of practices performed infectious disease screening of blood donors and evaluated hematologic variables prior to donation, but only one-third determined the donor blood type. None of the practices reported blood typing recipients, but this survey was performed prior to the availability of in-hospital dog erythrocyte antigen (DEA) 1 blood-type tests. Approximately half of the practices surveyed did not recover the costs of the transfusion, which was considered a lifesaving measure in 80% of cases (Howard et al. 1992).

Two decades later, a web-based survey was performed, which compiled information regarding blood donor and transfusion practices from 20 veterinary teaching hospitals and 53 private referral hospitals located in the United States, Canada, Europe, and Australia. This survey reflects the practice of a select number of specialty hospitals performing blood transfusions, as only emergency and critical care or internal medicine specialists (not general practitioners) were surveyed (Jagodich and Holowaychuk 2016). However, the information collected provides an idea of what the current transfusion and blood banking practices are amongst some veterinary hospitals worldwide, demonstrating how much transfusion practices have changed since the previous survey, performed more than 20 years earlier.

Current veterinary transfusion practices

The survey performed in 2012 provides information on transfusion practices used in specialty veterinary hospitals with regards to the blood products stored and/or administered, as well as recipient screening. PRBCs and FFP were the most frequently reported canine and feline blood products routinely purchased or collected by hospitals (Table 1.1), confirming a shift in transfusion practice from the collection and administration of whole blood to the routine use of component blood products (Jagodich and Holowaychuk 2016). This is in stark contrast to earlier transfusion practices as only 16% of previously surveyed small animal hospitals reported separating canine whole blood into components (Howard et al. 1992). Likewise, 96% of hospitals reported blood typing or crossmatching canine and feline recipients prior to blood product administration (Jagodich and Holowaychuk 2016), which is likely a reflection of the increase in knowledge and understanding of safe transfusion practices, as well as the availability of cage-side blood type kits, which were not available decades prior when routine recipient typing was not performed (Howard et al. 1992).

Table 1.1 Percentage of surveyed hospitals that reported how frequently they purchased or collected different canine and feline blood products (Jagodich and Holowaychuk 2016)

CP, cryoprecipitate; CPP, cryopoor plasma; FFP, fresh frozen plasma; FWB, fresh whole blood; HBOC, hemoglobin-based oxygen carrier; Lalb, lyophilized albumin; LCP, lyophilized cryoprecipitate; PC, platelet concentrate; PRBC, packed red blood cells; PRP, platelet-rich plasma; SWB, stored whole blood.

Current veterinary blood banking practices

The 2012 survey also provides information regarding the blood banking practices used in specialty veterinary hospitals, specifically concerning blood donor selection and screening. Approximately 50% of respondents reported using a combination of purchased blood products and hospital-run blood donor programs to provide canine blood products, whereas 19% of hospitals provided canine blood products using hospital-run blood donor programs only. The majority (85%) of those hospitals reported routinely using staff-owned dogs as blood donors with fewer respondents (53%) using client-owned dogs. Only 11% of hospitals reported having a colony of canine donors in the hospital (Jagodich and Holowaychuk 2016). These results differ substantially from previously reported practices, which rarely purchased blood products and more commonly used in-house dogs (Howard et al. 1992). The change over the years is likely due to the development of commercial blood banks and a shift in ethical beliefs regarding keeping in-hospital colonies of donor dogs.

Infectious disease screening of canine blood donors was routinely performed at 94% of hospitals with a hospital-run blood donor program and 53% reported blood typing canine donors for DEA 1 (Jagodich and Holowaychuk 2016). This also represents an increase in diligent blood donor screening compared to that which was reported previously, likely due to an improvement in knowledge and understanding regarding safe transfusion practices.

While feline blood donor practices have not been previously reported, the survey performed revealed that similar to dogs, half of all hospitals obtained blood products from a combination of purchased blood products and hospital-run blood donor programs, whereas 26% reported obtaining feline blood products using only a hospital-run blood donor program. Staff-owned cats were used by 73% of hospitals, compared to 40% of hospitals that reported having a colony of feline donors and 36% using client-owned cats. Routine screening of feline blood donors for infectious diseases was reported by 98% of survey respondents (Jagodich and Holowaychuk 2016). These findings demonstrate a slight difference in thought with regards to using colony feline versus canine donors, but a high diligence with regards to enforcing safe transfusion practices.

Advancements in veterinary transfusion medicine

Several advancements have been made in the field of veterinary transfusion medicine during recent years and will continue to be made as more well-designed research studies are published. A PubMed search using the terms transfusion, veterinary, and dog or cat yielded 426 publications in the field of small animal transfusion medicine between 1965 and 2015 (Figure 1.5). Of these publications, 161 were published within the last 10 years. It seems that whereas studies used to be sparse, articles pertaining to veterinary transfusion medicine are now being published on a routine basis. Likewise, there has been a shift towards more prospective studies rather than case reports or retrospective investigations. All of these publications have served to enhance knowledge in the field of veterinary transfusion medicine and encourage an evidence-based approach to transfusion practices.

c01f005

Figure 1.5 Graphical depiction of the number of veterinary publications related to transfusion medicine in dogs or cats.

Evidence-based guidelines

The evidence-based approach to formulating veterinary transfusion guidelines has culminated in the publication of a consensus statement by the ACVIM regarding blood donor screening. This consensus statement was drafted by a group of experts in the field of veterinary infectious disease and blood banking, and was first published more than 10 years ago (Wardrop et al. 2005). As a testament to the quickly growing body of research in the field of transfusion medicine, these guidelines were re-drafted and a preliminary view was provided at the ACVIM Forum in June 2015. The final recommendations were not published at the time of writing, but are anticipated to be published in 2016. Changes will likely reflect our increasing knowledge of infectious disease, including adjusted screening for feline leukemia virus (i.e., proviral DNA PCR testing) in cats, as well as banking samples from donors to allow retroactive testing.

The IAVBB is in the process of drafting and publishing veterinary blood banking standards modeled after guidelines provided by the AABB in the human field. These guidelines are expected to cover important details regarding the operation of a veterinary blood bank, such as the organizational structure, blood banking resources, equipment standards, supplier and customer issues, process control and improvement, documentation, facility standards, and safety. Without a doubt these guidelines will be the first of many to be published guiding veterinary transfusion and blood banking practices in the future.

Blood typing and recipient screening

Several advancements have also been made with regards to blood typing and recipient screening in dogs and cats. Whereas blood typing was previously only available at commercial laboratories and almost never performed at veterinary hospitals, the use of in-hospital blood type tests has become commonplace. This has served to improve the safety of blood transfusions administered in veterinary practice and likely has also enhanced the comfort level of practitioners administering blood products. Continued developments in this field have also improved typing methods, resulting in the availability of new canine and feline blood typing cartridges that use immunochromatographic test strips. Unlike agglutination card tests, the results of immunochromatographic tests can be interpreted even when auto-agglutination is present (Seth et al. 2012).

Other advancements in the field of blood typing include the discovery of new RBC antigens, including canine Dal and feline Mik (Blais et al. 2007; Weinstein et al. 2007). The detection of these antigens has changed recommendations with regards to donor and recipient screening, given that these antigens are not tested for by conventional blood typing methods. As such, some believe that all dogs and cats should routinely have a crossmatch performed prior to transfusions in order to maximize the potential to detect any incompatibilities not detected by conventional blood typing methods. This recommendation is emphasized by a recent study determining that feline red cell transfusion recipients that were blood type and crossmatch compatible had a higher post-transfusion increase in packed cell volume, compared to cats that were not crossmatched (Weltman et al. 2014).

The nomenclature of canine blood types has also recently changed, as it was discovered using flow cytometry that the DEA 1.2 and 1.3 blood types, which were previously thought to be different alleles, are likely a variation in the strength of monoclonal antibodies to DEA 1.1 (Acierno et al. 2014). Therefore, the nomenclature of DEA 1.1, 1.2, and 1.3 has become obsolete and is now described simply as DEA 1. This has already been reflected in a blood-type kit manufacturer's decision to rename the kit DEA 1, previously DEA 1.1 (DEA 1 Quick Test, Alvedia, France).

Transfusion triggers

Modification of the traditional transfusion triggers of 30/10 (packed cell volume 30%/hemoglobin 10 g/dL [100 g/L]) has occurred in human transfusion medicine in light of a multitude of studies demonstrating that a more conservative transfusion strategy (i.e., transfusing at a lower hemoglobin) is equal, if not superior, to the traditional and more liberal transfusion strategies (Carless et al. 2010). While research into the use of transfusion triggers is lacking in veterinary medicine, a scoring system has been developed to assist veterinarians in determining when a RBC transfusion might be warranted in anemic dogs (Kisielewicz et al. 2014). This score will likely guide veterinarians with less experience giving transfusions to more objectively determine when a transfusion might be warranted and also function to stratify patients being enrolled in future prospective transfusion studies.

Storage and administration of blood products

A relatively large number of studies investigating the effect of storage conditions and administration methods on the viability of veterinary blood products have been published in recent years. These include studies investigating various freeze-thaw conditions and storage temperatures on the activity of clotting factors in canine plasma products (Yaxley et al. 2010; Grochowsky et al. 2014; Walton et al. 2014; Pashmakova et al. 2015), as well as the impact of syringe or fluid pump administration methods on red blood cell viability (McDevitt et al. 2011; Heikes and Ruaux 2014). These studies, while experimental in nature, have improved our knowledge and understanding of the potential impact of storage, thawing, and administration methods on blood product viability and have immediate potential for clinical application.

Storage lesions and leukoreduction

Interest in storage lesions and the impact of the age of blood products on patient morbidity and mortality has recently increased (Obrador et al. 2015), along with research investigating the beneficial effects of pre-storage leukoreduction (McMichael et al. 2010; Graf et al. 2012; Herring et al. 2013; Corsi et al. 2014; Smith et al. 2015). There are also veterinary studies documenting the negative impact of administering older stored blood compared to blood stored for a shorter duration of time (Hann et al. 2014), while a clinical reduction in adverse effects associated with the use of leukoreduction filters has yet to be documented. As such, despite the relatively widespread use of leukoreduction in human medicine, routine use remains rare in veterinary medicine (Jagodich and Holowaychuk 2016). Likewise, the delineation of fresh versus old stored blood products is wrought with problems, including the increased disposal of expired blood products not used due to the negative connotations of stored red cell products (Holowaychuk and Musulin 2015). More information is needed with regards to the impact of storage lesions and leukoreduction on transfusion-related complications before firm recommendations can be made.

Therapies to reduce allogenic transfusions

Even though veterinarians are administering transfusions as safely as possible by performing diligent donor and recipient screening, and using appropriate administration and monitoring protocols, there is a growing concern regarding complications such as transfusion-related immunomodulation occurring secondary to allogenic transfusions (Hart et al. 2015). This has led to reports describing methods to reduce the administration of allogenic blood products. Examples include the use of specialized equipment such as cell salvage devices to enable safe and efficient autotransfusion of body cavity hemorrhage (Kellett-Gregory et al. 2013), as well as the administration of antifibrinolytic medication to ameliorate post-operative hemorrhage and transfusion requirements in predisposed breeds such as greyhounds (Marin et al. 2012a,b). It is likely that studies focused on reducing allogenic transfusions will continue to be performed as veterinarians seek out alternatives.

Future directions

Even though the number of veterinary studies published in the field of transfusion medicine is rapidly growing, there is still much work to be done and more knowledge to be gained in order to guide transfusion and blood banking practices. While retrospective studies have documented transfusion-related complications and demonstrated their association with a negative outcome, prospective studies are needed to further characterize what can be done to ameliorate these complications. Whether this will mean changing donor and recipient screening, adjusting transfusion triggers, using leukoreduction filters, altering blood storage and administration protocols, or seeking alternatives to allogenic transfusions remain to be determined.

Sourcing of sufficient donors to meet blood bank demands is also a consistent issue. Efforts to create wider public awareness of the need for donors, find an effective and sustainable supply of donated blood products, and use alternatives such as hemoglobin-based oxygen-carrying solutions and stem-cell derived RBCs, in addition to further refinement and widespread education regarding the appropriate use of blood products should help meet blood product demands. There is no doubt that the coming years will bring a plethora of veterinary publications that will serve to enhance knowledge and understanding of transfusion medicine and blood banking, enabling the creation of more evidence-based guidelines.

References

Acierno, M.M., Rai, K., and Giger, U. (2014) DEA 1 expression on dog erythrocytes analyzed by immunochromatographic and flow cytometric techniques. Journal of Veterinary Internal Medicine28, 592–598.

Blais, M.C., Berman, L., Oakley, D.A., and Giger, U. (2007) Canine Dal blood type: A red cell antigen lacking in some Dalmatians. Journal of Veterinary Internal Medicine21, 281–286.

Carless, P.A., Henry, D.A., Carson, J.L., et al. (2010) Transfusion thresholds and other strategies for guiding allogenic red blood cell transfusion. Cochrane Database of Systematic Reviews6, CD002042.

Corsi, R., McMichael, M.A., Smith, S.A., et al. (2014) Cytokine concentration in stored canine erythrocyte concentrates. Journal of Veterinary Emergency and Critical Care24, 259–263.

Crump, K.L. and Seshadri, R. (2009) Use of therapeutic plasmapheresis in a case of canine immune-mediated hemolytic anemia. Journal of Veterinary Emergency and Critical Care19, 375–380.

Farr, A.D. (1980) The first human blood transfusion. Medical History24,143–162.

Graf, C., Raila, J., Schweigert, F.J., and Kohn, B. (2012) Effect of leukoreduction treatment on vascular endothelial growth factor concentration in stored canine blood transfusion products. American Journal of Veterinary Research73, 2001–2006.

Greenwalt, T.J. (1997) A short history of transfusion medicine. Transfusion37, 550–563.

Grochowsky, A.R., Rozanski, E.A., deLaforcade, A.M., et al. (2014) An ex vivo evaluation of efficacy of refrigerated canine plasma. Journal of Veterinary Emergency and Critical Care24, 388–397.

Hann, L., Brown, D.C., King, L.G., and Callan, M.B. (2014) Effect of duration of packed red blood cell storage on morbidity and mortality in dogs after transfusion: 3,095 cases (2001–2010). Journal of Veterinary Internal Medicine28, 1830–1837.

Hart, S., Cserti-Gazdewich, C.M., and McCluskey, S.A. (2015) Red cell transfusion and the immune system. Anaesthesia70, 38–45.

Heikes, B.W. and Ruaux, C.G. (2014) Effect of syringe and aggregate filter administration on survival of transfused autologous fresh feline red blood cells. Journal of Veterinary Emergency and Critical Care24, 162–167.

Herring, J.M., Smith, S.A., McMichael, M.A., et al. (2013) Microparticles in stored canine RBC concentrates. Veterinary Clinical Pathology42, 163–169.

Holowaychuk, M.K. and Musulin, S.E. (2015) The effect of blood usage protocol on the age of packed red blood cell transfusions administered at two veterinary teaching hospitals. Journal of Veterinary Emergency and Critical Care25, 679–683.

Howard, A., Callan, B., Sweeney, M., and Giger, U. (1992) Transfusion practices and costs in dogs. Journal of the American Veterinary Medical Association201, 1697–1701.

Jagodich, T.A. and Holowaychuk, M.K. (2016) Transfusion practice in dogs and cats: an internet-based survey. Journal of Veterinary Emergency and Critical Care Jan 27. doi: 10.1111/vec.12451 [Epub ahead of print].

Kellet-Gregory, L.M., Seth, M., Adamantos, S., and Chan, D.L. (2013) Autologous canine red blood cell transfusion using cell salvage devices. Journal of Veterinary Emergency and Critical Care23, 82–86.

Khorzad, R., Whelan, M., Sisson, A., and Shelton, G.D. (2011) Myasthenia gravis in dogs with an emphasis on treatment and critical care management. Journal of Veterinary Emergency and Critical Care21, 193–208.

Kisielewicz, C., Self, I., and Bell, R. (2014) Assessment of clinical and laboratory variables as a guide to packed red blood cell transfusion of euvolemic anemic dogs. Journal of Veterinary Internal Medicine28, 576–582.

Landsteiner, K. (1961) On agglutination of normal human blood. Transfusion1, 5–8.

Marín, L.M., Iazbik, M.C., Zaldivar-Lopez, S., et al. (2012a) Epsilon aminocaproic acid for the prevention of delayed postoperative bleeding in retired racing greyhounds undergoing gonadectomy. Veterinary Surgery41, 594–603.

Marín, L.M., Iazbik, M.C., Zaldivar-Lopez, S., et al. (2012b) Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation bleeding in retired racing greyhounds with appendicular bone tumors: 46 cases (2003–2008). Journal of Veterinary Emergency and Critical Care22, 322–340.

McCullough, J. (2003) Introduction to Apheresis donations including history and general principles. In: Apheresis: Principles and Practice (ed. B. McLeod), pp. 29–47. AABB Press, Bethesda, MD.

McCullough, J. (2012) Transfusion Medicine. Wiley-Blackwell, Chichester.

McDevitt, R.I., Ruaux, C.G., and Baltzer, W.I. (2011) Influence of transfusion technique on survival of autologous red blood cells in the dog. Journal of Veterinary Emergency and Critical Care21, 209–216.

McMichael, M.A., Smith, S.A., Galligan, A., et al. (2010) Effect of leukoreduction on transfusion-induced inflammation in dogs. Journal of Veterinary Internal Medicine24, 1131–1137.

Murphy, S. and Gardner, F.H. (1969) Platelet preservation – effect of storage temperature on maintenance of platelet viability – deleterious effect of refrigerated storage. New England Journal of Medicine380, 1094–1098.

Nakamura, R.K., Tompkins, E., and Blanco, D. (2012) Therapeutic options for immune-medicated thrombocytopenia. Journal of Veterinary Emergency and Critical Care22, 59–72.

Nakao, M., Nakao, T., Arimatsu, Y., et al. (1960) A new preservative medium maintaining the level of adenosine triphosphate and the osmotic resistance of erythrocytes. Proceedings of the Japan Academy36, 43–47.

Obrador, R., Musulin, S., and Hansen, B. (2015) Red blood cell storage lesion. Journal of Veterinary Emergency and Critical Care25, 187–199.

Pashmakova, M.B., Barr, J.W., and Bishop, M.A. (2015) Stability of hemostatic proteins in canine fresh-frozen plasma thawed with a modified commercial microwave warmer or warm water bath. American Journal of Veterinary Research76, 420–425.

Pool, J.G. and Shannon, A.E. (1965) Simple production of high potency anti-hemophilic globulin (AHG) concentrates in a closed bag system. Transfusion5, 372.

Seth, M., Jackson, K.V., Winzelberg, S., and Giger, U. (2012) Comparison of gel column, card, and cartridge techniques for dog erythrocyte antigen 1.1 blood typing. American Journal of Veterinary Research73, 213–219.

Simon, E.R., Chapman, R.G., and Finch, C.A. (1962) Adenine in red cell preservation. Journal of Clinical Investigation41, 351–359.

Smith, S.A., Ngwenyama, T.R., O'Brien, M., et al. (2015) Procoagulant phospholipid concentration in canine erythrocyte concentrates stored with or without prestorage leukoreduction. American Journal of Veterinary Research76, 35–41.

Walton, J.E., Hale, A.S., Brooks, M.B., et al. (2014) Coagulation factor and hemostatic protein content of canine plasma after storage of whole blood at ambient temperature. Journal of Veterinary Internal Medicine28, 571–575.

Wardrop, K.J., Reine, N., Birkenheuer, A., et al. (2005) Canine and feline blood donor screening for infectious disease. Journal of Veterinary Internal Medicine19, 135–142.

Weinstein, N.M., Blais, M.C., Harris, K., et al. (2007) A newly recognized blood group in domestic shorthair cats: the Mik red cell antigen. Journal of Veterinary Internal Medicine21, 287–292.

Weltman, J.G., Fletcher, D.J., and Rogers, C. (2014) Influence of cross-match on posttransfusion packed cell volume in feline packed red blood cell transfusion. Journal of Veterinary Emergency and Critical Care24, 429–436.

Yaxley, P.E., Beal, M.W., Jutkowitz, L.A., et al. (2010) Comparative stability of canine and feline hemostatic proteins in freeze-thaw-cycled fresh frozen plasma. Journal of Veterinary Emergency and Critical Care20, 472–478.

Zimring, J.C. (2009) Leukoreduction of blood products. In: Transfusion Medicine and Hemostasis (eds C.D. Hillyer, B.H. Shaz, J.C. Zimring, et al.), pp. 215–218. Elsevier, Burlington, MA.

Chapter 2

Component Therapy

Julie M. Walker

Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA

Introduction

Blood collected from a donor can be utilized in many ways. Although a unit of whole blood (WB) can be transfused or stored after collection without further processing, separation of the unit into blood components can provide several benefits. This chapter provides an explanation of component therapy as it compares to the transfusion of WB, highlighting the advantages and disadvantages of these practices. A general overview of the most commonly administered blood components will also be provided.

Whole blood

Description and contents

Veterinary hospitals and blood banks that practice traditional blood banking begin by collecting a standardized volume of blood from a donor, which is immediately mixed with an anticoagulant-preservative solution as it flows into the primary collection container. At the time of collection, WB contains all components of circulating blood including red blood cells (RBCs) and white blood cells (WBCs), platelets, coagulation factors, albumin, globulins, electrolytes, etc., at concentrations that were present in the donor. This product, known as fresh whole blood (FWB), can be transfused immediately or stored briefly (<8 hours) at room temperature prior to transfusion. WB can also be stored at 4 °C (stored whole blood, SWB) for up to 35 days depending on the anticoagulant-preservative solution used, or can be processed into blood components (Bucheler and Cotter 1994; Callan 2010).

Platelets in FWB maintain the ability to aggregate for at least 8 hours when stored at room temperature (Tsuchiya et al. 2003). However, platelet aggregation and factor V and VIII concentrations in SWB decrease in a time-dependent manner during storage at 4 °C (Nilsson et al. 1983; Nolte and Mischke 1995; Solheim et al. 2003; Jobes et al. 2011; Pidcoke et al. 2013).

Indications

The transfusion of FWB is indicated for the treatment of anemia that occurs concurrently with coagulopathy, thrombopathia, or severe thrombocytopenia. Patients with severe traumatic injury and marked hemorrhage who require massive transfusion might also benefit from a FWB transfusion (Kauvar et al. 2006; Repine et al. 2006; Spinella 2008; Spinella et al. 2009; Cotton et al. 2013). Similarly, SWB is indicated for the treatment of anemia with coagulopathy, but this product would not be appropriate to correct thrombocytopenia, thrombopathia, or deficiency of factors V or VIII. WB, while not ideal, can also be administered to patients with euvolemic non-coagulopathic anemia, particularly when component therapy is not readily accessible.

Advantages

The most notable advantages of collecting and transfusing WB are availability and practicality for private practices that infrequently administer blood transfusions. With proper understanding of transfusion principles, identification of a healthy blood donor and proficiency in venipuncture and aseptic technique, FWB collection and transfusion can be safely performed in most veterinary settings. If SWB will be kept for later use, the hospital must use a refrigerator that can consistently maintain a constant temperature between 1 and 6 °C. Conversely, FWB can be collected in a more flexible manner when used immediately; the phlebotomist can even draw the desired amount of blood into syringes that have been pre-filled with anticoagulant-preservative solution. This practice allows the collection of only the desired volume of blood, but is inappropriate for long-term storage as this method utilizes an open collection system, which limits storage time to less than 24 hours (Roback et al. 2011).

Disadvantages

Being able to perform blood donation at the time of patient need makes it necessary to complete comprehensive health and infectious disease screening on donors well in advance of donation. It can be challenging to find blood donors that are available at all times for blood donation on an on call basis. When a patient has an urgent need for a blood transfusion, the delay in treatment that occurs while contacting the blood donor's owner, awaiting donor arrival, and collecting the FWB unit can also be a significant disadvantage. Additionally, the administration of FWB or SWB to anemic patients without hypovolemia or coagulopathy predisposes recipients to volume overload and antigenic stimulation secondary to unnecessary plasma administration. Because of this, banking and administration of component therapy has several advantages over FWB and SWB.

Component therapy

Background concepts

The separation of WB into its constituents for further storage prior to administration is known as component therapy. FWB can be processed into a variety of different components that can be transfused based on individual patient need (Table 2.1). Most established in-hospital and commercial blood banks are able to create these WB-derived components. While most veterinary blood banks process components by centrifugation of collected blood, specific blood components can also be collected directly from a donor using apheresis, an extracorporeal process that employs differential centrifugation within a tubing system to selectively collect one or more blood components (e.g., platelets or plasma), while immediately returning the unused portion to the donor. There has been an increase in the use of apheresis for the collection of RBC, platelet, and plasma units from human blood donors in the United States from 2008 to 2011 (Department of Health and Human Services 2013). The production of apheresis-derived components requires access to and experience with specialized equipment, therefore these techniques are performed in only a small number of commercial animal blood banks and veterinary teaching hospitals.

Table 2.1 Overview of blood products, including contents, indications, and storage conditions

RBC, red blood cells; WBC, white blood cells; vWF, von Willebrand Factor.

a Minimal leukocyte content if leukoreduction techniques are applied.

b Shelf life depends on the anticoagulant-preservative solution used.

c Controversial.

Lyophilization, simply the process of freeze drying, has also been used to preserve and extend the shelf-life of blood products. During the process of lyophilization, the prepared blood product is injected into a vial and loaded onto a lyophilizer, where it undergoes rapid freezing. After the product is frozen, it is heated under very low (subatmospheric) pressure conditions, causing sublimation of the solvent from its frozen (solid) phase directly to its gas phase. The water vapor is removed by the machine, leaving behind a dry product that can later be reconstituted for use (Fetterolf 2010). At this time, lyophilized canine albumin and cryoprecipitate products have been produced by a commercial blood bank (Animal Blood Resources International, Stockbridge, MI) for clinical use and lyophilized canine platelets have been used in a research setting (Davidow et al. 2012).

Instrumentation for blood component production

Over the past 30 years, there has been a significant increase in the transfusion