UNASSIGNED: Decreasing rates of blood donation and close margins between blood supply and demand pose challenges in healthcare. Genetically engineered pig red blood cells (pRBCs) have been explored as alternatives to human RBCs for transfusion, and triple-gene knockout (TKO) modification improves the compatibility of pRBCs with human blood in vitro. In this study, we assessed the efficacy and risks of transfusing wild-type (WT)- and TKO-pRBCs into nonhuman primates (NHPs).
UNASSIGNED: Blood from O-type WT and TKO pigs was processed to produce pRBCs for transfusion, which were transfused or not into NHPs (n=4 per group: WT, TKO, and control) after 25% total blood volume withdrawal: their biological responses were compared. Hematological, biochemical, and immunological parameters were measured before, immediately after, and at intervals following transfusion. Two months later, a second transfusion was performed in three NHPs of the transfusion group.
UNASSIGNED: Transfusion of both WT- and TKO-pRBCs significantly improved RBC counts, hematocrit, and hemoglobin levels up to the first day post-transfusion, compared to the controls. The transfusion groups showed instant complement activation and rapid elicitation of anti-pig antibodies, as well as elevated liver enzyme and bilirubin levels post-transfusion. Despite the higher agglutination titers with WT-pRBCs in the pre-transfusion crossmatch, the differences between the WT and TKO groups were not remarkable except for less impairment of liver function in the TKO group. After the second transfusion, more pronounced adverse responses without any hematological gain were observed.
UNASSIGNED: WT- and TKO-pRBC transfusions effectively increased hematologic parameters on the first day, with rapid clearance from circulation thereafter. However, pRBC transfusion triggers strong antibody responses, limiting the benefits of the pRBC transfusion and increasing the risk of adverse reactions.

OBJECTIVE: To evaluate the major crossmatch compatibility between rabbit recipients, rabbit donors, and the major canine and feline blood types.
METHODS: Prospective in vitro study in December 2021.
METHODS: Academic veterinary teaching hospital.
METHODS: 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.
METHODS: 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-1-negative, feline type A, and feline type B.
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.

The global shortage of human blood for medical use has prompted the development of alternative blood sources. Nonhuman primates (NHPs) are commonly used owing to their physiological similarities to humans. The objective of the current study was to establish a controlled-blood-loss model in NHPs to explore their clinical and biological responses.
Blood was sequentially withdrawn from 10 cynomolgus monkeys (10, 14, 18, 22, and 25% of the total blood volume); their vital signs were monitored, and blood parameters were serially analyzed. Humoral mediators in the blood were measured using flow cytometry and enzyme-linked immunosorbent assays.
In NHPs subjects to 25% blood loss and presenting with related clinical symptoms, the systolic blood pressure ratio on day 0 after bleeding was significantly lower than that of the animals from the other groups (median: 0.65 vs. 0.88, P = 0.0444). Red blood cell counts from day 0-14 and hematocrit levels from day 0-7 were markedly decreased relative to the baseline (P < 0.01). These parameters showed a direct correlation with the extent of blood loss. The levels of creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase exhibited increases in response to blood loss and had a stronger correlation with the hemoglobin ratio than the volume of blood loss. The levels of C3a and C4a, as well as interleukin (IL)-1α and IL-15, displayed a strong correlation, with no apparent association with blood loss.
The findings of the present study showed that only NHPs with 25% blood loss exhibited clinical decompensation and significant systolic blood pressure reduction without fatalities, suggesting that this level of blood loss is suitable for evaluating blood transfusion efficacy or other treatments in NHP models. In addition, the ratio of hemoglobin may serve as a more dependable marker for predicting clinical status than the actual volume of blood loss. Thus, our study could serve as a basis for future xenotransfusion research and to predict biological responses to massive blood loss in humans where controlled experiments cannot be ethically performed.

Transfusion of allogeneic human red blood cell (hRBCs) is limited by supply and compatibility between individual donors and recipients. In situations where the blood supply is constrained or when no compatible RBCs are available, patients suffer. As a result, alternatives to hRBCs that complement existing RBC transfusion strategies are needed. Pig RBCs (pRBCs) could provide an alternative because of their abundant supply, and functional similarities to hRBCs. The ability to genetically modify pigs to limit pRBC immunogenicity and augment expression of human \'protective\' proteins has provided major boosts to this research and opens up new therapeutic avenues. Although deletion of expression of xenoantigens has been achieved in genetically-engineered pigs, novel genetic methods are needed to introduce human \'protective\' transgenes into pRBCs at the high levels required to prevent hemolysis and extend RBC survival in vivo. This review addresses recent progress and examines future prospects for clinical xenogeneic pRBC transfusion.

UNASSIGNED: To describe the management of post-operative abdominal hemorrhage with a xenotransfusion of canine lyophilized platelets in a feline patient.
UNASSIGNED: A 9-year-old male castrated domestic shorthair presented for a spontaneous hemoabdomen secondary to hepatic amyloidosis. Clinically significant hemorrhage occurred in the perioperative and post-operative period and the patient received a massive transfusion and anti-fibrinolytic therapy in combination with a xenotransfusion of canine lyophilized platelets at 0.9 × 109 particles/kg and recombinant human factor VIIa (rhFVIIa). The combination of these interventions decreased transfusion requirements in this patient and the xenotransfusion was well tolerated with no acute or immediate transfusion reactions noted.
UNASSIGNED: This case report describes the xenotransfusion of canine lyophilized platelets in a feline patient with severe, non-compressible abdominal hemorrhage.

The platelet-rich plasma (PRP) has become popular in the medical world due to its content of growth factors and numerous studies are experimental. In experimental studies, the preparation and application of PRP are problematic and allogenic PRP transfers have been preffered, because of the difficulties in preparation of autogenic PRP in animal experiments. Xenogenic transfers and their effects have not been studied in this topic. This study aimed to investigate the effect of autogenic and xenogenic use of PRP on composite graft viability.Methods: Two composite grafts are prepared for each ear of nine rabbits. Each ear was randomly divided into three groups. After the procedure, the wound edges and base were injected with 1 cc serum physiologic, autogenic PRP or 1 cc human-derived xenogenic PRP. At 3 weeks, samples were taken, photographic and histopathological evaluations were made.Results: The graft viability was better in autogenic and xenogenic group compared to the control group. In comprasion of autogenic and xenogenic groups, although the macroscopic evaluation revealed better graft viability and less necrosis in the group which had been treated with autogenic PRP, the difference was not statistically significant. The three groups did not significantly differ in terms of inflammation. Vascularization examined histopathologically. CD31 staining, which was used to evaluate angiogenesis, was significantly higher in the autogenic PRP group than the remaining two groups.Conclusion: Although autogenic PRP has better results histopathologically, the xenogenic use of PRP may be an alternative for studies, when macroscopic evaluation is necessary.

The aim of this study was to report the incidence of transfusion reactions in cats, including acute haemolysis (AH), occurring within 24 h of receiving a xenotransfusion. An additional aim was to determine whether cases with AH could be classified as having an acute haemolytic transfusion reaction (AHTR) as per the definition provided by the Association of Veterinary Haematology and Transfusion Medicine\'s Transfusion Reaction Small Animal Consensus Statement.
Medical records of cats that received canine packed red blood cells (PRBCs) between July 2018 and September 2020 at a veterinary hospital were reviewed. The incidence of AH, AHTRs, febrile non-haemolytic transfusion reactions (FNHTRs), transfusion-associated circulatory overload and septic transfusion reactions were recorded.
The medical records of 53 cats were retrospectively evaluated. Twenty-three (43%) cats had transfusion reactions. Thirteen (25%) cats had AH; however, only four (8%) met the definition of an AHTR. Ten (19%) cats were determined to have FNHTRs. Survival to discharge of cats affected by AH was 50% (25% for cases that met the definition of an AHTR). Survival to discharge of cats not suffering from AHTR was 40%.
This report indicates that a higher proportion of cats undergo AH (25%) when administered canine PRBCs than previously reported, although many could not be classed as having an AHTR due to an apparently adequate packed cell volume rise. Challenges with sourcing feline blood in emergency situations occasionally necessitates the use of xenotransfusion in transfusion medicine. Clinicians should be aware that haemolysis after xenotransfusion can occur within 24 h and that a repeat feline transfusion may be required sooner than anticipated in some cases.

Despite the ability to determine feline blood types, the transfusion of canine blood to cats is still practiced in some countries. Xenotransfusion is effective-even if its effects only last for a few days-and is not associated with serious adverse effects. It avoids the need for blood typing, and most importantly, it avoids the transmission of intraspecific infectious agents, notably the feline leukemia virus (FeLV). Transfusion with canine blood is easier, quicker and less costly than transfusion with feline blood; it is less disagreeable for the donor. In the light of these arguments, when feline blood collected according to current guidelines is not available, in particular when the donor is not confirmed to be negative for the FeLV provirus, the authors consider it to be judicious to use canine blood for feline transfusion in emergency situations; this practice is preferable to inaction and to the inoculation of an infectious agent. Allotransfusion remains preferable in non-emergency situations as a treatment of chronic compensated anaemiae or if an appropriate donor (negative for FeLV provirus) is available. However, 2-4 days after a xenotransfusion, if a clinical alteration and a significant decrease in haematocrit are observed, a transfusion with cat\'s blood confirmed to be negative for FeLV provirus should be performed. Xenotransfusion should never be used twice.

OBJECTIVE: To determine the in vitro compatibility of rabbit and canine blood using both a tube and slide agglutination crossmatch technique and to compare the results obtained from these 2 methods.
METHODS: Prospective observational laboratory study from January to March 2020.
METHODS: University veterinary teaching hospital.
METHODS: Six client-owned rabbits ≥3.5 kg undergoing phlebotomy for a clinical reason. \"Pigtail\" blood samples from 3 dog erythrocyte antigen (DEA) 1-positive and 3 DEA 1-negative canine packed red blood cell units.
METHODS: Blood from each rabbit was crossmatched with a single unit of canine blood using both a standard laboratory tube agglutination technique and a simple slide agglutination method with each rabbit/canine unit serving as its own intraassay control. Tube crossmatches were evaluated for agglutination both macro- and microscopically and assessed for hemolysis. Slide crossmatches were assessed for the presence of agglutination both macro- and microscopically.  MEASUREMENTS AND MAIN RESULTS: All crossmatches were incompatible. Varying degrees of agglutination were seen for all crossmatches. Hemolysis was observed with all minor tube crossmatches. Results of both crossmatch techniques were in close agreement.  CONCLUSIONS: The crossmatch results in this present study strongly demonstrate in vitro incompatibility between canine and rabbit blood. Agreement between the 2 techniques in this study indicates that the slide agglutination technique may be quicker, require less blood, and provide reliable results in exclusively assessing the compatibility of canine and rabbit blood. Based on the results of this study, emergency xenotransfusion of canine blood to rabbits cannot be recommended.

BACKGROUND: Blood transfusion remains important in the treatment of patients with sickle cell disease (SCD). However, alloimmunization after blood transfusion is associated with patient morbidity and mortality. Triple-knockout (TKO) pigs (i.e., pigs in which the three known xenoantigens to which humans have anti-pig antibodies have been deleted) may be an alternative source of RBCs for these patients because many humans have no preformed antibodies to TKO pig RBCs (pRBCs).
METHODS: In an in vitro study, plasma from alloimmunized (n = 12) or non-alloimmunized (n = 12) SCD patients was used to determine IgM/IgG binding to, and CDC of, TKO pRBCs. In an in vivo study, after an estimated 25% of blood volume was withdrawn from two capuchin monkeys, CFSE-labeled TKO pRBCs were transfused. Loss of TKO pRBCs was monitored by flow cytometry, and 7 weeks later, 25% of blood was withdrawn, and CFSE-labeled monkey RBCs were transfused.
RESULTS: The in vitro study demonstrated that plasma from neither alloimmunized nor non-alloimmunized SCD patients bound IgM/IgG to, or induced CDC of, TKO pRBCs. In the in vivo study, survival of TKO pRBCs in the two capuchin monkeys was of 5 and 7 days, respectively, whereas after allotransfusion, survival was >28 days.
CONCLUSIONS: In conclusion, (1) in the present limited study, no antibodies were detected that cross-reacted with TKO pRBCs, and (2) TKO pigs may possibly be an alternate source of RBCs in an emergency if no human RBCs are available.