VET Augustus / August 2024 The Monthly Magazine of the SOUTH AFRICAN VETERINARY ASSOCIATION Die Maandblad van die SUID-AFRIKAANSE VETERINÊRE VERENIGING Osteosarcoma in a dog.... CPD THEME Cats nuus•news CPD article QR code
Dagboek • Diary Ongoing / Online 2024 August 2024 SAVETCON: Webinars Info: Corné Engelbrecht, SAVETCON, 071 587 2950, corne@savetcon.co.za / https://app.livestorm.co/svtsos Acupuncture – Certified Mixed Species Course Info: Chi University: https://chiu.edu/courses/cva#aboutsouthafrica@tcvm.com SAVA Johannesburg Branch CPD Events Monthly - please visit the website for more info. Venue: Johannesburg Country Club Info: Vetlink - https://savaevents.co.za/ SAVA Western Cape Branch Congress 02-03 August Venue: Protea Hotel, Technopark, Stellenbosch Info: www.vetlink.co.za Understanding Alpacas Seminar 04-05 August Venue: The Alpaca Visitors' Centre, Walkerville, Gauteng Info: Alison 0826629670 or alpacas@helderstroom.co.za Understanding Alpacas Seminar 09-10 August Venue: Helderstroom Alpacas Stud, Villiersdorp, WC Info: Alison 0826629670 or alpacas@helderstroom.co.za SAVA Oranje Vaal Branch Mini Congress - POSTPONED 09-10 August Venue: Khaya Ibhubesi, Parys Info: conference@savetcon.co.za NVCG Bush Break 12-13 August Venue: Skukuza, Kruger National Park Info: https://vetlink.co.za/nvcg-2024/ 21st Annual SASVEPM Congress 21-23 August Venue: Lagoon Beach Hotel, Cape Town Info: Vetlink: https://sasvepm.org/sasvepm-congress-2024/ September 2024 October 2024 November 2024 SAVA Eastern Free State Branch Mini Congress 06-07 September Venue: Protea Hotel, Clarens Info: conference@savetcon.co.za SAVA Eastern Cape and Karoo Branch CPD Day 07 September Venue: Dolphins Leap, Port Elizabeth Info: www.vetlink.co.za 8th World One Health Congress 20-23 September Venue: CTICC, Cape Town, South Africa Info: https://globalohc.org/8WOHC or contact conferences@vetlink.co.za SAVA Northern Natal and Midlands Branch Congress 05-06 October Venue: Lythwood Lodge, Midlands Info: www.vetlink.co.za PARSA Conference 06 – 08 October Venue: Villa Paradiso, Hartbeespoort, Gauteng Info: corne@savetcon.co.za SAAVT 2024 Conference 09 – 10 October Venue: 26 Degrees South, Muldersdrift Info: conference@savetcon.co.za or https://savetcon.co.za/2024-saavt-biennial-congress/ 12th IAVRPT Symposium 30 October – 02 November Venue: Somerset-West, Cape Town, South Africa Info: https://iavrpt2024.co.za/ or contact conferences@vetlink.co.za Poultry Group of SAVA Annual Congress 06-08 November Venue: 26 Degrees South, Muldersdrift, Gauteng Info: conferences@savetcon.co.za https://savetcon.co.za/poultry2024/
Vetnuus | August 2024 1 Contents I Inhoud President: Dr Paul van der Merwe president@sava.co.za Managing Director: Mr Gert Steyn md@sava.co.za/ +27 (0)12 346 1150 Editor VetNews: Ms Andriette van der Merwe vetnews@sava.co.za Bookkeeper: Ms Susan Heine accounts@sava.co.za/+27 (0)12 346 1150 Bookkeeper's Assistant: Ms Sonja Ludik bookkeeper@sava.co.za/+27 (0)12 346 1150 Secretary: Ms Elize Nicholas elize@sava.co.za/ +27 (0)12 346 1150 Reception: Ms Hanlie Swart reception@sava.co.za/ +27 (0)12 346 1150 Marketing & Communications: Ms Sonja van Rooyen marketing@sava.co.za/ +27 (0)12 346 1150 Membership Enquiries: Ms Debbie Breeze debbie@sava.co.za/ +27 (0)12 346 1150 Vaccination booklets: Ms Debbie Breeze debbie@sava.co.za/ +27 (0)12 346 1150 South African Veterinary Foundation: Ms Debbie Breeze savf@sava.co.za/ +27 (0)12 346 1150 Community Veterinary Clinics: Ms Claudia Cloete cvcmanager@sava.co.za/ +27 (0)63 110 7559 SAVETCON: Ms Corné Engelbrecht corne@savetcon.co.za/ +27 (0)71 587 2950 VetNuus is ‘n vertroulike publikasie van die SAVV en mag nie sonder spesifieke geskrewe toestemming vooraf in die openbaar aangehaal word nie. Die tydskrif word aan lede verskaf met die verstandhouding dat nóg die redaksie, nóg die SAVV of sy ampsdraers enige regsaanspreeklikheid aanvaar ten opsigte van enige stelling, feit, advertensie of aanbeveling in hierdie tydskrif vervat. VetNews is a confidential publication for the members of the SAVA and may not be quoted in public or otherwise without prior specific written permission to do so. This magazine is sent to members with the understanding that neither the editorial board nor the SAVA or its office bearers accept any liability whatsoever with regard to any statement, fact, advertisement or recommendation made in this magazine. VetNews is published by the South African Veterinary Association STREET ADDRESS 47 Gemsbok Avenue, Monument Park, Pretoria, 0181, South Africa POSTAL ADDRESS P O Box 25033, Monument Park Pretoria, 0105, South Africa TELEPHONE +27 (0)12 346-1150 FAX General: +27 (0) 86 683 1839 Accounts: +27 (0) 86 509 2015 WEB www.sava.co.za CHANGE OF ADDRESS Please notify the SAVA by email: debbie@sava.co.za or letter: SAVA, P O Box 25033, Monument Park, Pretoria, 0105, South Africa CLASSIFIED ADVERTISEMENTS (Text to a maximum of 80 words) Sonja van Rooyen assistant@sava.co.za +27 (0)12 346 1150 DISPLAY ADVERTISEMENTS Sonja van Rooyen assistant@sava.co.za +27 (0)12 346 1150 DESIGN AND LAYOUT Sonja van Rooyen PRINTED BY Business Print: +27 (0)12 843 7638 VET nuus•news Diary / Dagboek II Dagboek • Diary Regulars / Gereeld 2 From the President 4 Editor’s notes / Redakteurs notas Articles / Artikels 8 Major crossmatch compatibility of rabbit blood with rabbit,canine, and feline blood 13 Exploring the TumorAssociated Risk of Mesenchymal Stem Cell Therapy in Veterinary Medicine Association / Vereniging 24 CVC News 28 In Memoriam 38 Legal Mews Events / Gebeure 16 Fauresmith 2024 26 The 2024 Presidents award - Prof G Bath 30 Onderstepoort: the Ladies of Old Res Vet's Health / Gesondheid 36 Life Coaching Technical / Tegnies 37 Royal Canin Column 40 Dental Column Relax / Ontspan 20 Opinion Piece 22 Letter to the Editor 48 Life Plus 25 Marketplace / Markplein 42 Marketplace Jobs / Poste 44 Jobs / Poste 46 Classifieds / Snuffeladvertensies 16 30 26 44 Scan the QR code for easy access to this month's CPD article «
Vetnews | Augustus 2024 2 « BACK TO CONTENTS “We are each other’s harvest” means that when we nurture one another, we all benefit, or reap the rewards of another’s success. The veterinary profession is seemingly under constant threats and challenges from governmental institutions, regulatory bodies, nongovernmental organisations, associations, the public, and most sadly from our very own colleagues. Some examples of these threats/ challenges that SAVA acted upon recently: • The prohibition of Yohimbine, the limitations placed on oxygen supplies and the banning of Trilostane by SAHPRA. • The ongoing saga by the Department of Health on trying to prevent veterinarians from dispensing and compounding. • The decisions regarding vaccinations and vaccine control. • The CCS program limiting foreign veterinarians from working in South Africa. • Remunerative Work Outside Public Service. • The removal of veterinarians from the Critical Skills List. • Veterinarians as essential health workers. • Developments around a secondary faculty with the possibility of a private faculty. • The control of scheduled drugs. • Improving relations with regulatory bodies and associations. • Numerous outbreaks of diseases contributed to breaks in biosecurity. • Continuous outcry about fees. • Lack of teaching staff at the faculty. • Wildlife Welfare Forum and the proposed banning of lions in captivity. • Active participation in mental health programs to establish best practices for our members. • Active participation in international veterinary bodies. Despite these efforts funded by a small group (60 % of South African veterinarians) and managed by an even smaller core of volunteers, every veterinarian in South Africa benefits from the successes of SAVA. To be an even stronger voice of the veterinarian, SAVA needs to represent ALL veterinarians in South Africa. We need to nurture one another to the benefit of all to reap the rewards of another’s success. The future of veterinary services lies in the unity of the profession which is promoted by the vision and mission of SAVA. It is now time that we all stand together to make a difference and protect our noble profession. Vis unita fortior – Strength in Unity. May this be our motto for the future? Let us put our differences behind us and work united towards maintaining and advancing the veterinary profession despite our differences. SAVA is the only organisation that can take it forward. Rather than asking what SAVA can do for you, ask what will become of the profession if SAVA is no more! (1) From the Essential Gwendolyn Brooks (Library of America, 2005). Copyright © 1970 by Gwendolyn Brooks. v Kind regards, Paul van der Merwe From the President Dear members, That time we all heard it, cool and clear, cutting across the hot grit of the day. The major Voice. The adult Voice forgoing Rolling River, forgoing tearful tale of bale and barge and other symptoms of an old despond. Warning, in music-words devout and large, that we are each other’s harvest: we are each other’s business: we are each other’s magnitude and bond. (1)
Vetnuus | August 2024 3 To find out more: Building better practice, together. The co.mpanion partnership is a co.llaborative model that gives you the ownership, support and autonomy you need to build your individual practice’s legacy inside a growing network. co.mpanion is not a corporate body, it is a professional owned and led veterinary model that is right for you if: You are looking for a support structure. You are looking for a better way to exit from or sell your practice. You want to become a shareholder. www.companion.partners Download Value Proposition View Video WhatsApp
Vetnews | Augustus 2024 4 « BACK TO CONTENTS Taking a break We just returned from a 2-week road trip to the Kgalagadi with dear friends. This happened just days after our daughter (#NextgenerationVeterinarian #proudparents) got married in our home town, Hoedspruit. Joining us were long-time friends from Belgium. On our way back this picture popped up on my Fb page. It is not in my nature to believe in coincidence. Two things popped up for me. The one is how important travel for a person is. I met a young girl in the city of Kuruman working in a leather shop. She was born and raised there but had a dream to au-pair internationally. I could not encourage her enough to grab the opportunity, gather up the courage to take the next step and explore the world. Back to our time in the Kgalagadi: there is very little to no cellphone signal, Wifi internet is available at R75 for 400Mb. I knew I had to prepare the next Vetnews and realised I had to do most of the work even before the wedding. Fortunately, the pages of Vetnews are filled by wonderful trustworthy people which meant that most of the work could be done beforehand. Thanks to all of you – ed. Being without an internet connection can be pretty uncomfortable because who is used to conversations any more? (silly smiley face). BUT, resting can mean a break from not only social media but also being unavailable for work stuff and preparing for it. I read in an article on www.verywellmind.com the following: Taking a break from work is essential, and yet many people leave their vacation time unused.1 Whether you plan a vacation, a staycation, or a playcation, it’s essential to take a break from your job, your routine, and the demands of life to keep stress levels in check. When you take a break, you’re not shirking responsibility. You’re taking care of yourself so you’ll have the stamina to be your best. By learning the signs that you need a break, you’ll know when to schedule some time away to help you feel refreshed and restored. Taking a break from work is vital if you want to manage stress and avoid burnout. Signs that you might need to take a break include feeling cynical, exhausted, or withdrawn. By taking a break, whether it’s a vacation or just a short break during the day, you can come back to your work with a fresher, more rested mind. That got me thinking that the best break you can take is from news and social media. In the ‘old’ days we used to come up to Kruger pretty often, be it for work or vacation. I remember distinctly leaving my emotional baggage, hurt, sorrow etc at Oom Paul’s bust at Kruger gate. The time in the Park was without any ‘outside’ disturbances or influences. When it was time to leave, I was ready to pick up whatever I left at the gate and face reality again. Yes, it was before connection to the world was simply held in your hand, therefore I think we have a greater responsibility to take a break from being in touch with the world and rather focus on ourselves when we take time out. Be encouraged to take leave and also be fair to those working for you to get enough rest to also keep the stress levels under control. In this month’s magazine, there is a heartfelt obituary to Dr Fritz Zollner; one of our own receives a prestigious award; the next chapter in the Onderstepoort History series and some recent research on cats. Enjoy the read. v Andriette From the Editor Editor’s notes / Redakteurs notas
Vetnuus | August 2024 5 “The South African Veterinary Association aims to serve its members and to further the status and image of the veterinarian. We are committed to upholding the highest professional and scientific standards by utilising the professional knowledge, skill and resources of our members, to foster close ties with the community and thus promote the health and welfare of animals and mankind”. MISSION STATEMENT Servicing and enhancing the veterinary community since 1920! Tel: 012 346 1150 E-mail: vethouse@sava.co.za www.sava.co.za STUDY VETERINARY MEDICINE IN CYPRUS DOCTOR OF VETERINARY MEDICINE (DVM) 5-Year Programme for High School Leavers unic.ac.cy/vet EARLY CLINICAL EXPOSURE AND TRAINING in small groups with both large and small animals from year one. CURRICULUM ALIGNED WITH RCVS, AVMA, EAEVE, AND WORLD ORGANIZATION FOR ANIMAL HEALTH INNOVATIVE, HANDS-ON CURRICULUM designed to offer you the necessary Day One skills required to follow any career pathway in veterinary medicine. COMMUNITY SERVICE AND ANIMAL WELFARE volunteerism and service opportunities with sheltered animals. TALENTED AND DEDICATED FACULTY MEMBERS AND STAFF facilitating and guiding your learning and development as a veterinarian. FINANCIAL AID SCHOLARSHIPS AVAILABLE
Vetnews | Augustus 2024 6 « BACK TO CONTENTS
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Vetnews | Augustus 2024 8 « BACK TO CONTENTS Abstract Objective: To evaluate the major crossmatch compatibility between rabbit recipients, rabbit donors, and the major canine and feline blood types. Design: Prospective in vitro study in December 2021. Setting: Academic veterinary teaching hospital. Animals: Whole blood samples were collected from 11 healthy New Zealand White rabbits (Oryctolagus cuniculus) with no previous transfusion history. Three pigtail segments were acquired from dog erythrocyte antigen (DEA)-1-positive, DEA-1-negative, and feline type A blood units.Whole blood was collected from a healthy type B blood donor cat. Interventions: Blood from each rabbit recipient underwent a major crossmatch using standard tube crossmatch methodology with itself and the following donor blood types: rabbit, DEA-1-positive, DEA-1negative, feline type A, and feline type B. Measurements and Main Results: Self-crossmatches and crossmatches between rabbit recipients and conspecific donors were negative for hemolysis and agglutination. Crossmatches between rabbit recipients and canine and feline donors yielded no hemolysis but produced varying degrees of macroscopic and microscopic agglutination. Rabbit recipients had 1.4 (95% confidence interval: 1.1–1.8) times the risk of macroscopic agglutination when major crossmatched with canine blood compared to feline blood. No significant difference in agglutination was found between DEA-1-positive and DEA-1-negative or feline type A and type B donors. Conclusions: These findings support allogeneic blood transfusions between rabbits being highly compatible and suggest rabbits have naturally occurring alloantibodies against both canine and feline red blood cells. However, feline red blood cells had a lower rate of in vitro incompatibility on major crossmatch, suggesting potentially higher in vivo compatibility if an emergency xenotransfusion is needed. Further prospective research is needed to determine if xenotransfusion is associated with a higher incidence of acute and delayed transfusion reactions in rabbits than allogeneic transfusions. Abbreviations: DEA, dog erythrocyte antigen; PBS, phosphate-buffered saline; pRBC, packed red blood cells. 1. INTRODUCTION Given the growing popularity of zoological companion animals, many of these unique species, including rabbits (Oryctolagus cuniculus), are increasingly presented in need of critical care. Numerous disease processes in rabbits may result in severe anemia and the potential need for a blood transfusion, including trauma, liver lobe torsion, and coccidiosis.1 To date, there are no widely clinically recognized blood types in rabbits. In addition, commercial rabbit blood products or rabbit blood banks have not been established. If a conspecific blood donor rabbit is not readily available or facilitating a blood donation delays transfusion, a blood transfusion from another species (ie, xenotransfusion) may be a life-saving alternative. Emergency xenotransfusion between domestic animal blood donors and zoological animal recipients has been previously described, including canine whole blood to an island fox (Urocyon littoralis),2 bovine packed red blood cells (pRBCs) to a bluewildebeest (Connochaetes taurinus),3 and feline pRBCs to a ferret (Mustela furo).4 Crossmatch testing is performed to minimize the risk of immunemediated hemolytic transfusion reactions and alloimmunization, prolong donor RBC life span, and improve blood transfusion efficacy.5–8 While blood typing can determine the presence of known RBC surface antigens (ie, allo-antigens), crossmatch testing can help determine if a patient has in vitro serological compatibility with a potential blood donor. Major and minor crossmatch testing assesses in vitro serological compatibility between a blood transfusion recipient and a potential blood donor by assessing for hemolysis and agglutination. Hemolysis occurs when alloantibodies (ie, antibodies against foreign RBC allo-antigens) trigger complement and subsequent RBC membrane disruption, whereas agglutination results from alloantibodies binding RBC allo-antigens crosslinking them.8 A major crossmatch tests for naturally occurring or induced alloantibodies in the recipient’s serum or plasma against donor RBCs; conversely, a minor crossmatch tests for naturally occurring or induced alloantibodies in the donor’s serum or plasma against recipient RBCs.5–8 Major crossmatch compatibility of rabbit blood with rabbit,canine, and feline blood Nicholas G. Dannemiller DVM SarahM.Ozawa DVM, DACZM Olivia A. Petritz DVM, DACZM Sarah E. Musulin DVM, DACVECC Department of Clinical Sciences, College of VeterinaryMedicine, North Carolina State University, Raleigh, North Carolina, USA Correspondence SarahM.Ozawa, College of Veterinary Medicine, North Carolina State University, 1060 WilliamMoore Drive, Raleigh, NC 27607, USA. Email: sozawa@ncsu.edu
Vetnuus | August 2024 9 If hemolysis or agglutination occurs in either crossmatch, a potential in vivo serological incompatibility may exist between the recipient and blood donor.5–8 The minor crossmatch is considered less clinically important for component therapy but is recommended when transfusing whole blood or plasma.7 Stored canine and feline blood products are frequently available at referral and veterinary specialty centers, making their potential availability for an emergency xenotransfusion to a rabbit recipient likely. Dog erythrocyte antigen (DEA)-1-positive, DEA-1-negative, feline type A, and feline type B (albeit rare) blood products may be potential options for transfusion of an anemic rabbit. While a recent experimental study evaluated the in vitro serological compatibility of rabbit recipients and canine blood products,9 no study has explored the in vitro serological compatibility of rabbit recipients and rabbit or feline blood donors. Similarly, no current evidence suggests that canine or feline blood products would be more compatible. The objective of this study was to evaluate the in vitro major crossmatch compatibility between rabbit recipients, rabbit donors, and canine and feline blood donors of different major blood types. The authors hypothesized that rabbit blood donors would have better in vitro serological compatibility than canine and feline blood donors. Given a previously successful case report in a ferret,4 the authors also hypothesized that feline blood donors would have better in vitro serological compatibility than canine blood donors. 2. METHODS 2.1 Rabbit recipients Blood samples were collected from 11 (9 females, 2 males) juvenile New Zealand White rabbits (Oryctolagus cuniculus) from 2 institutions previously used for clinical teaching or research. Full ethical approval was granted by the 2 institutions’ Institutional Animal Care and Use Committees prior to phlebotomy. All rabbits were 4–5 months old, weighed 4.1–5.4 kg (median: 4.62 kg), were apparently healthy on physical exam, and had no previous transfusion history. For 5 rabbits, 1–2 mL of blood was collected from the left or right lateral saphenous vein under gentle manual restraint via 1-in 25-Ga needles and 3-mL syringes. For the other 6 rabbits, 2 mL of blood was collected via direct intracardiac sampling under injectable anesthesia immediately before euthanasia via 1.5-in 21-Ga needles and 3-mL syringes. Injectable anesthesia was achieved with ketamine (35 mg/kg, IM)a and xylazine (5 mg/ kg, IM).b All blood samples were placed into EDTA microtainers or vacutainers and refrigerated (2–80C) until crossmatching within 2–4 hours of collection. 2.2 Blood product donors Rabbit recipients also served as conspecific rabbit blood donors using the previously detailed blood samples. Feline blood donors were from the authors’ academic veterinary teaching hospital blood donor cat colony and were previously blood typed using a commercial point-of-care immunochromatographic assay.c Canine blood donors were client-owned animals previously blood typed via a commercial laboratory.d All donors met the criteria outlined in the current American College of Veterinary Internal Medicine consensus statement on canine and feline blood donor screening for bloodborne pathogens.10 Three pigtail segments (aliquots of blood attached to the outside of a blood product unit used for crossmatching) were acquired from pRBC units from DEA-1-positive canine donors, DEA-1-negative canine donors, and feline type A donors collected within 1month prior to this study. Canine pRBC units contained the anticoagulant citrate– phosphate–dextrose, as well as a preservative solution containing adenine, dextrose, sorbitol, sodium chloride, and mannitol (ADSOL), and were stored at 2–50C. Feline pRBC units contained the anticoagulant– preservative solution citrate–phosphate–dextrose–adenine and were stored at 2–50C. Whole blood (~3 mL) was collected from a type B feline blood donor via the external jugular vein and placed into an EDTA vacutainer. 2.3 Major crossmatch procedure The major crossmatch procedure was adapted from a published veterinary protocol6 and the mammalian crossmatch standard operating procedure used by the authors’ veterinary teaching hospital clinical pathology laboratory. All crossmatches were performed and interpreted by an experienced nonblinded individual (NGD) within 2–4 hours of rabbit blood collection. Microtainers or vacutainers containing rabbit blood were acclimated to room temperature and centrifuged at 1000 × g for 10 minutes. Rabbit plasma was pipetted off and placed in a plastic transfer tube. Rabbit plasma hemolysis, icterus, and lipemia were assessed as absent, slight, mild, moderate, and gross compared with a visual key. Recipient 3% RBC suspensions were made for each rabbit. Using a calibrated pipette, 100 μL of blood was removed from the spun down microtainers or vacutainers and dispensed into a 12- × 75-mm glass tube labeled with the rabbit’s identification number. Recipient RBCs were resuspended by adding a small amount of phosphate-buffered saline (PBS) and mixing gently. The tube was filled three-fourths full of PBS, centrifuged for 60 seconds at 1000 × g, and the resulting supernatant was decanted, leaving a washed RBC pellet. This was repeated for a total of 3 washes. After the final wash, approximately 3 mL of PBS was added to the washed RBC pellet to produce a 3% RBC suspension. Donor 3% RBC suspensions were made for each blood type. Pigtail segments were pierced via a segment splitter, and approximately 2–3 drops of blood were squeezed into a 12- × 75-mm glass tube labelled with the respective blood type. For the feline type B 3% RBC suspension, 100 μL of blood was removed from the spun down vacutainer and dispensed into a labeled 12- × 75-mm glass tube. Donor RBCs were resuspended, washed 3 times, and used to produce a 3% RBC suspension as previously described. Blood from rabbit recipients underwent a major crossmatch with blood from each canine and feline blood donor type and 1 rabbit donor. Blood from rabbit recipients and rabbit donors was randomly paired via an online random pair generator.e For internal quality control, each rabbit sample underwent a major crossmatch with itself twice. Using disposable pipettes, 2 drops of rabbit plasma followed by 1 drop of the respective donor’s 3% RBC suspension were placed in a 12- × 75-mm glass tube labeled with the rabbit’s identification number and donor’s blood type. Tubes were gently mixed and centrifuged for 20 seconds at 1000 × g. The presence of hemolysis was interpreted compared with the rabbit recipient’s original plasma. The RBC pellet was gently resuspended, and the presence of macroscopic agglutination was interpreted with the aid of a macroscopic agglutination lamp reader. If no macroscopic agglutination was found, the tube was examined for microscopic agglutination using a tube holder and direct microscopy. Tubes were incubated at 370C for 30 minutes using a heat block and centrifuged for 20 seconds at 1000 × g. The presence of hemolysis and agglutination was interpreted as previously described. Hemolysis was graded as present or absent. Macroscopic agglutination was graded on a previously described scale of absent to 4+.6 Microscopic agglutination was graded as present or absent. >>> 10 Leading Article
Vetnews | Augustus 2024 10 « BACK TO CONTENTS 2.4 Statistical analysis Nonparametric statistical tests were employed due to the ordinal nature of the dependent variables (eg, hemolysis and agglutination grading). The occurrence of hemolysis and agglutination for rabbit recipients was compared between donor species using a Kruskal–Wallis test, followed by pairwise comparisons using a Wilcoxon ranksum test. Differences in the occurrence of hemolysis and agglutination for rabbit recipients between feline and canine blood types were compared using a Wilcoxon rank-sum test. The occurrence of hemolysis and agglutination pre- and postincubation at 370C for 30 minutes was also compared using a Wilcoxon rank-sum test. If applicable, the relative risk of hemolysis and agglutination between canine and feline blood donors and types was calculated. For all statistical tests, null hypotheses were rejected when P-values were <0.05. All calculations and analyses were performed in the statistical software Rf using the “dplyr,” “tidyr,” and “epitools” packages and their dependents. 3. RESULTS A total of 77 major crossmatches were performed. All internal quality controls (ie, self-crossmatches) were negative for hemolysis and macroscopic and microscopic agglutination (Table 1). All major crossmatches between rabbit recipients and canine and feline blood donors were negative for hemolysis but produced varying degrees of macroscopic and microscopic agglutination (Table 1). For DEA-1-negative and DEA-1-postive donors, 100% (11/11) of rabbit recipients had 1+ macroscopic agglutination post-incubation at 370C for 30 minutes. For feline type A donors, 36% (4/11) of rabbit recipients had weak positive macroscopic agglutination, 55% (6/11) had 1+ macroscopic agglutination, and 9% (1/11) had microscopic agglutination post-incubation at 370C for 30 minutes. For feline type B donors, 9% (1/11)of rabbit recipients had weak positive macroscopic agglutination,45.5% (5/11) had 1+ macroscopic agglutination, and 45.5% (5/11) had microscopic agglutination postincubation at 370C for 30 minutes. All major crossmatches between rabbit recipients and donor conspecifics were negative for hemolysis and macroscopic and microscopic agglutination (Table 1). A Kruskal–Wallis test found a significant difference in the occurrence of agglutination between donor species (P < 0.001). Wilcoxon rank-sum test pairwise comparisons found significant differences in the occurrence of agglutination between canine and rabbit donors (P < 0.001), feline and rabbit donors (P < 0.001), and canine and feline donors (P < 0.001). Major crossmatches with canine and feline donors resulted in significantly higher occurrences of agglutination than rabbit donors (P < 0.001, respectively), and major crossmatches with canine donors resulted in a significantly higher occurrence than feline donors (P < 0.001). Major crossmatches with canine donors had 1.4 (95% confidence interval: 1.1–1.8) times the risk of macroscopic agglutination compared with feline donors. No significant difference in agglutination was found between canine blood types and feline blood types; similarly, no significant difference in agglutination was found pre- and post-incubation across all crossmatches. 4. DISCUSSION If a blood donor rabbit is not readily available, an emergency xenotransfusion with canine or feline blood products to a severely anemic rabbit may be a life-saving alternative. This study is the first to report the major crossmatch compatibility between blood of rabbit recipients, rabbit donors, and the 4major canine and feline blood types. No hemolysis or agglutination in all major crossmatches between rabbit donors and recipients was identified, supporting this study’s first hypothesis and potentially suggesting a high likelihood of in vivo serological compatibility between rabbits. Leading Article Preincubation Postincubation Agglutination Agglutination Blood donor Hemolysis Macroscopi Microscopic Hemolysis Macroscopi Microscopic Self (controls) Absent 0/11 (0%) Absent 0/11 (0%) Absent 0/11 (0%) Absent 0/11 (0%) Absent 0/11 (0%) Absent 0/11 (0%) Rabbit Absent 0/11 (0%) Absent 0/11 (0%) Absent 0/11 (0%) Absent 0/11 (0%) Absent 0/11 (0%) Absent 0/11 (0%) DEA 1+ Absent 0/11 (0%) W+ 1/11 (9%) N/A Absent 0/11 (0%) 1+ 11/11 (100%) N/A DEA 1− Absent 0/11 (0%) 1+ 11/11 (100%) N/A Absent 0/11 (0%) 1+ 11/11 (100%) N/A Feline type A Absent 0/11 (0%) W+ 5/11 (45%) 1+ 4/11 (37%) Present 2/11 (18%) Absent 0/11 (0%) W+ 4/11 (36%) 1+ 6/11 (55%) Present 1/11 (9%) Feline type B Absent 0/11 (0%) W+ 2/11 (18%) 1+ 4/11 (37%) Present 5/11 (45%) Absent 0/11 (0%) W+ 1/11 (9%) 1+ 5/11 (45.5%) Present 5/11 (45.5%) TABLE 1: The major crossmatch compatibility between rabbit recipients (n = 11), rabbit donors, and canine and feline blood donors of different major blood types: DEA-1-positive, DEA-1-negative, feline type A, and feline type B. Note: Rabbit recipients also served as conspecific rabbit blood donors. Major crossmatches were interpreted pre- and post incubation at 370C for 30 minutes to assess for any delayed hemolysis or agglutination. Hemolysis and microscopic agglutination were graded as present or absent. Macroscopic agglutination was graded on a scale of absent, weak positive (W+), 1+, 2+, 3+, or 4+ as follows: W+ = very small, barely visible agglutination with a turbid background of free RBCs; 1+ = obvious small agglutinates with a turbid background of free RBCs; 2+ = medium-sized agglutinates present with a clear background; 3+=several large agglutinates; 4+=1 solid agglutinate with no free RBC.
Vetnuus | August 2024 11 Leading Article Although no hemolysis was observed, microscopic to macroscopic agglutination in all major crossmatches between canine or feline donors and rabbit recipients was present, and canine donors had 1.4 times the risk of macroscopic agglutination than feline donors. These results suggest that rabbits have naturally occurring alloantibodies against both canine and feline RBC alloantigens and support this study’s second hypothesis that feline RBCs may have better serological compatibility than canine RBCs. Possible explanations for this potential difference include the density and immunogenicity of species-specific RBC alloantigens (eg, DEA-1) and the specificity and cross-reactivity of naturally occurring rabbit alloantibodies. In terms of comparative hematology, rabbit RBCs exhibit a typical mammalian, anucleated, biconcave disc morphology similar to canine and feline RBCs.11 However, rabbits have higher RBC turnover and a predicted random destruction rate of 0.5% per day, resulting in an average life span of 45–70 days.11 Rabbit RBC life span is thus more similar to feline RBCs (66–72 days) and approximately half that of canine RBCs (110–120 days). Despite rabbit hemostasis being similar, generally, to other mammals, rabbit blood hemolyzes easily and clots quickly, which may complicate phlebotomy for crossmatches and blood donation.11 While there are >300 breeds of domestic rabbits, all are descendants of a single species, the European rabbit (Oryctolagus cuniculus), originally native to the Iberian Peninsula.11 Although there are no widely clinically recognized blood types in rabbits, it is possible potential rabbit RBC alloantigens and naturally occurring alloantibodies exist in varying prevalence among different domestic rabbit breeds and geographically distinct populations similar to domestic dogs. A single colony of laboratory rabbits was shown to develop varying titers of alloantibodies after repeated allogeneic blood transfusions, suggesting recipient sensitization occurs in rabbits similar to other mammals.12 Further investigations performing crossmatches between rabbit recipients and donors of different rabbit breeds could improve our understanding of rabbit blood types and allogeneic transfusions. The main disadvantages of xeno-transfusion across species includes documented decreased donor RBC survival, putative increased risk of transfusion reactions, and recipient sensitization. In experimental studies in domestic cats, the average transfused RBC survival was <4 days with canine xenotransfusions, whereas the average transfused RBC survival reached 30–38 days with autotransfusions or compatible allogeneic blood transfusions.13,14 A recent multicenter, prospective, observational study found that canine xeno-transfusion to feline patients resulted in no acute adverse reactions other than self-limiting, febrile, nonhemolytic transfusion reactions.15 However, 25 of 39 (64%) feline patients developed delayed hemolytic transfusion reactions within 1–6 days after xenotransfusion.15 Subsequent canine xenotransfusion to cats >6 days after initial transfusion has led to severe anaphylactic reactions and death.16,17 In cockatiels (Nymphicus hollandicus) transfused with whole blood from blue-fronted Amazon parrots (Amazona aestiva) and pigeons (Columba livia), xeno-transfusion resulted in a shorter survival of transfused RBCs (<3 days), whereas no difference was found in RBC survival between autotransfusions and allogeneic blood transfusions (10–17 days).18 Similarly, in sun conure (Aratinga solstitialis) transfused with whole blood from white-eyed conures (Psittacara leucophthalmus), transfused RBCs had decreased survival (4.5 days) compared with RBC survival after autotransfusions and allogeneic blood transfusions (8.5–10 days).19 In the limited number of case reports of xeno-transfusion in nondomestic species, no acute or delayed transfusion reactions were observed.2–4 To the authors’ knowledge, there are no case reports of serial xenotransfusions and subsequent recipient sensitization in rabbits. Further prospective research is needed to determine if xenotransfusion is associated with a higher incidence of acute and delayed transfusion reactions in rabbits than allogeneic transfusions. Given the higher RBC turnover observed in rabbits coupled with decreased RBC survival shown in other species receiving xenotransfusions, an emergency xeno-transfusion may only potentially aid a rabbit recipient for a short duration. These findings build on a similar recent observational study that evaluated the major and minor crossmatch compatibility between DEA-1-positive and DEA1-negative RBCs and rabbit recipients.9 Similar to the results of the current study, Cutler et al found all major crossmatches between canine donors and rabbit recipients resulted in macroscopic agglutination; however, the macroscopic agglutination observed was more variable and severe (1+ to 4+).9 This variability could be due to differences in rabbit populations, blood sample and donor collection, or subtle differences in tube crossmatch methodology. While crossmatch incompatibility is predictive of acute transfusion reactions in some studies, the degree of incompatibility (eg, agglutination grade) is not predictive of life-threatening acute transfusion reactions.5,20 Cutler et al found that all minor crossmatches between canine donors and rabbit recipients resulted in hemolysis, suggestive of naturally occurring canine alloantibodies against rabbit RBCs.9 No minor crossmatches were performed in this study given the difficulty of extracting a reliable volume of donor plasma from pigtails.Currently, there is insufficient evidence for, or against, minor crossmatching in canine and feline transfusion medicine.21 The minor crossmatch has almost universally been discontinued in human pretransfusion testing due to enhanced human blood donor screening and the increasing use of blood component therapy versus whole blood transfusions.22 While there are multiple internationally recognized canine blood groups categorized under the DEA system, DEA-1 is considered the most clinically significant in canine transfusion medicine. Although titers of naturally occurring anti-DEA-1 alloantibodies have not been identified, sensitization of DEA-1-negative dogs with DEA-1positive RBCs can lead to acute hemolytic transfusion reactions.23 In feline transfusion medicine, the AB blood group system is most commonly used in clinical practice, with type A cats having low titers of naturally occurring anti-B alloantibodies, whereas type B cats have high titers of naturally occurring anti-A alloantibodies.5,7 Similar to a previous study,9 the current study found no significant difference in agglutination between DEA-1-positive and DEA1-negative crossmatched to rabbit recipient blood. The current study additionally found no significant difference between feline type A and type B blood donors. These data suggest that rabbits may have naturally occurring alloantibodies against canine and feline RBC alloantigens other than or in addition to DEA-1, type A, or type B. The significant difference in agglutination between canine and feline donors suggests that rabbits’ alloantibodies may target, or bind with variable affinity, different RBC alloantigens between the 2 species. While the biochemical and genetic basis for the feline AB blood group system has been characterized, the DEA system has not been characterized to the same degree, and other RBC alloantigens have been recently found (eg, Dal, Kai 1, Kai 2).8 In a recent multicenter, prospective, observational study, no significant difference in crossmatch incompatibility or transfusion reactions was found between feline patients receiving canine xenotransfusions with DEA-1-positive or DEA-1-negative blood.15 >>> 12
Vetnews | Augustus 2024 12 « BACK TO CONTENTS Together, these findings suggest that while blood group systems play an important role in allo geneic blood transfusions within species, they likely hold little predictive or clinical use in xenotransfusion across species. Traditional tube crossmatch methodology typically requires up to 2 mL of EDTA-anticoagulated whole blood, which may be difficult, if not impossible, in small zoological companion animals.24 Safe phlebotomy in zoological companion animals is typically limited to 1% of their respective total body weight, which may often be <1 mL. Consequently, simplified major and minor crossmatches have been employed using a slide agglutination test in which drops of the recipient and donor serum, plasma, or whole blood are mixed on a glass slide at room temperature and examined under a microscope.24 A previous study compared simplified major and minor crossmatches with standard tube crossmatch methodology in rabbits and found close agreement.9 While simplified major and minor crossmatches predict potential agglutination, they cannot predict hemolysis or account for the role temperature plays in alloantibody–alloantigen reactions.24 Hemolysis is considered more clinically significant than agglutination, given that it is suggestive of in vivo intravascular hemolysis, which can result in a systemic inflammatory response, hemodynamic instability, multiple organ dysfunction, and death.8 The alloantibody– alloantigen reactions believed to be most clinically significant in vivo occur at body temperature (warm agglutinins) rather than at room temperature (cold agglutinins).8,9 While the clinical significance of warm and cold agglutinins is not known in rabbits, this study found no significant difference in agglutination pre- and post-incubation across all crossmatches. Although it does not predict hemolysis, simplified crossmatches using a slide agglutination test at room temperature may be a reliable pretransfusion method in rabbits to assess agglutination. Pretransfusion testing in human medicine is highly regulated by governmental and professional healthcare organizations (eg, Federal Drug Administration, American Association of Blood Banks); however, similar stringency and standardization do not currently exist in veterinary medicine.5 As a result, subtle differences exist in major and minor tube crossmatch procedures and interpretation between veterinary emergency and critical care medicine references and referral centers. While the clinical significance of these in vivo differences is unknown, they pose a more immediate potential limitation in comparing and synthesizing in vitro transfusion medicine research. In human transfusion medicine, gel column technology has quickly replaced tube crossmatch methodology due to its many advantages, including speed, standardization, smaller sample volume, and enhanced sensitivity and specificity.25 Although tube crossmatches may be more affordable and accessible to veterinary researchers, gel column crossmatching in veterinary medicine is growing,6,8 and its application to xeno-transfusion across species should be investigated in the future. While this study focused on the 4 major canine and feline blood types historically and most frequently available at referral and veterinary specialty centers, other DEA antigens, the canine Dal antigen, the canine antigens Kai 1 and Kai 2, and the feline Mik antigen could be confounding factors.5,8 Different canine and feline blood-typing methodologies and assays have varying sensitivity and specificity, which could have falsely identified the canine and feline blood donors used in this study. Rabbit recipients only underwent a major crossmatch with 1 randomly assigned rabbit donor due to the finite plasma available. A larger sample size of rabbit recipients and a greater number of crossmatches could have strengthened this study’s findings. The healthy New Zealand White rabbits used in this study were a relatively homogeneous study population in terms of rabbit breed, strain, age, and environmental conditions, which may be different than the heterogeneous population of pet rabbits presented in need of critical care. Although crossmatches were performed and interpreted within 2–4 hours of rabbit blood collection, performing them immediately after phlebotomy could have minimized any potential artifact due to delayed processing. While an autotransfusion or allogeneic blood transfusion is preferred, an emergency xeno-transfusion may provide crucial time for a compatible conspecific donor to be found, a diagnosis to be made, or a patient to respond to therapeutic intervention. This study supports allogeneic blood transfusions between rabbits being highly compatible and builds on the current understanding that rabbits have in vitro serological incompatibility to canine and feline RBCs. This study also suggests rabbits have less in vitro serological incompatibility to feline RBCs if an emergency xeno-transfusion is truly needed. The in vivo serological compatibility and subsequent risk of transfusion reactions in rabbits receiving xeno--transfusions with canine or feline blood products remain unclear. Clinicians should continue to carefully weigh pretransfusion testing with the therapeutic needs of a severely anemic rabbit. A major crossmatch (via tube or simplified methodology) is recommended prior to xenotransfusion to a rabbit recipient, knowing that donor RBC survival will likely be decreased, and the degree of any in vitro crossmatch incompatibility may not be predictive of in vivo serological compatibility. ACKNOWLEDGMENTS The authors thank Andrea Thompson, Alexis Sluder, Coralie Zegre Cannon, and Alicia Ossi for their assistance in sample collection, as well as Lynnette McCall, Charlotte Shaughnessy, and the North Carolina State University College of Veterinary Medicine Clinical Pathology Laboratory for providing equipment, laboratory space, and crossmatch expertise. The authors also thank the amazing canine and feline blood donors whose generous contributions make the North Carolina State University College of Veterinary Medicine Blood Bank possible. v CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest. ORCID Nicholas G. DannemillerDVM https://orcid.org/0000-0003-3429- 1881 SarahM.OzawaDVM,DACZM https://orcid.org/0000-0002-9038- 8795 Sarah E.MusulinDVM,DACVECC https://orcid.org/0000-0002- 5420-0601 ENDNOTES aKetaset Zoetis Inc., Kalamazoo, MI. bXylaMed MWI Animal Health, Boise, ID. c QuickTest A+B Alvedia, Limonest, France. d Animal Blood Resources International, Stockbridge,MI. e https://pairs. austincodingacademy.com/ fR Core Team, Vienna, Austria. Leading Article References available on request.
Vetnuus | August 2024 13 Exploring the Tumor-Associated Risk of Mesenchymal Stem Cell Therapy in Veterinary Medicine Soyoung Jeung 1,2, Sungsoo Kim 1,2 , Jaegon Ah 1, Sanghyuk Seo 1, Umair Jan 3 , Hyejin Lee 4 and Jeong Ik Lee 3,4,* 1 VIP Animal Medical Center, 73, Dongsomun-ro, Seongbuk-gu, Seoul 02830, Republic of Korea; jeungs1007@gmail.com (S.J.); ilovekh0@vipah.co.kr (S.K.); sadgon@hanmail.net (J.A.); ssh45035@vipah.co.kr (S.S.) 2 Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea 3 Regenerative Medicine Laboratory, Center for Stem Cell Research, Department of Biomedical Science and Technology, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Republic of Korea; umairjan47@konkuk.ac.kr 4 Department of Veterinary Obstetrics and Theriogenology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; hyejinly@konkuk.ac.kr * Correspondence: jeongik@konkuk.ac.kr Simple Summary: This report discusses the ongoing research on, and concerns regarding, the tumor promotion associated with multipotent stem cells, with a focus on mesenchymal stem cells (MSCs) in regenerative medicine. Throughout this commentary, we explore the various impacts of MSC therapies on tumor growth that occurs in veterinary analysis. Additionally, we investigated the characteristics that rendered embryonic stem cells and induced pluripotent stem cells more tumorigenic than MSCs. Overall, despite concerns regarding tumorigenesis, limited evidence supports the increased risk of tumors associated with MSC injections. MSCs are thus considered a valuable and safe alternative in the veterinary medicine market, especially for companion animals such as dogs and cats. Moreover, bioengineered MSC-derived exosomes are preferable choices for tumor diagnosis and treatment. Abstract: Mesenchymal stem cell (MSC) therapy has been actively applied in veterinary regenerative medicine to treat various canine and feline diseases. With increasing emphasis on safe cell-based therapies, evaluations of their tumorigenic potential are in great demand. However, a direct confirmation of whether tumors originate from stem cells or host cells is not easily achievable. Additionally, previous studies evaluating injections of high doses of MSCs into nude mice did not demonstrate tumor formation. Recent research focused on optimizing MSC-based therapies for veterinary patients, such as MSC-derived extracellular vesicles in treating different diseases. This progress also signifies a broader shift towards personalized veterinary medicine, where treatments can be tailored to individual pets based on their unique genetic profiles. These findings related to different treatments using MSCs emphasize their future potential for veterinary clinical applications. In summary, because of lower tumor-associated risk of MSCs as compared to embryonic and induced pluripotent stem cells, MSCs are considered a suitable source for treating various canine and feline diseases. 1. Introduction Multipotent mesenchymal stem cells (MSCs) derived from bone marrow were first identified in 1961 [1]. Stem cells have since been actively researched for several years in both human and veterinary medicine, and commercial stem cell therapy for equine orthopedic diseases commenced in 2003 [2]. As a cornerstone of regenerative medicine, stem cell therapy has primarily been used to treat cellular damage and refractory diseases in dogs and cats [3]. However, recently, its therapeutic scope has gradually expanded, with a notable emphasis on its anti-inflammatory and immunomodulatory capabilities [4–6]. Stem cell therapy in dogs and cats utilizes either in-clinic cell production or the use of approved veterinary medical products. Japan introduced the first allogeneic adiposederived MSC-based pharmaceutical (Stemcure®, Osaka, Japan), and the UK pioneered a xenogeneic stem cell-based pharmaceutical (DogStem®, Oxfordshire, UK) using equine umbilical cord-derived MSCs, primarily for use in dogs [7,8]. Safety plays a pivotal role as a prerequisite and a fundamental element in decision making related to stem cell therapy [9]. Previous research has suggested that the side effects of stem cell therapy are minimal, generally mild, and self-limiting over a short period [10]. However, the tumor-associated risk of MSCs remains uncertain; thus, to ensure safe stem cell therapy, there is a need to assess the risk of tumorigenesis and tumor promotion. Animal model research simulates naturally occurring human diseases and is driven by the extensive parallels between animals and humans in comparative medicine [11–13]. Ongoing research has explored the tumorigenesis of MSCs after invivo injections as well as their impact on tumor growth. Moreover, some studies have demonstrated the contributions of animal models in studying human diseases, providing numerous similarities between human and companion animals [14–20]. Considering these aspects, in this commentary, our focus is on exploring the research on the tumorassociated risk of stem cell therapies in companion animals, as based on insights from human biology and medicine. The aim of this study is to thoroughly assess the safety of MSC therapy by examining it from multiple perspectives. This involves analyzing its distinct characteristics and comparing its safety profile with that of embryonic stem cells and induced pluripotent stem cells, as well as the risk associated with tumors. Additionally, this study seeks to explore how MSCs can be effectively applied in stem cell therapy. >>> 14
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