Abstract
Xenotransfusion (the transfusion of blood from another species) of canine blood to cats has been historically performed commonly and is still performed nowadays in some countries. Considering the current lack of commercial availability of haemoglobin-based oxygen carrier solution (Oxyglobin), there may be rare occasions when treating an anaemic cat when compatible feline blood cannot be obtained, and where a transfusion with canine blood may need to be considered as a life-saving procedure. This article reviews the published evidence about feline xenotransfusion with canine blood and the results that can be expected with this procedure. Published evidence in a limited number of cases (62 cats) indicates that cats do not appear to have naturally-occurring antibodies against canine red blood cell antigens: compatibility tests prior to the first transfusion did not demonstrate any evidence of agglutination or haemolysis of canine red cells in feline serum or plasma. No severe acute adverse reactions have been reported in cats receiving a single transfusion with canine whole blood. Anaemic cats receiving canine blood are reported to improve clinically within hours. However, antibodies against canine red blood cells are produced rapidly and can be detected within 4–7 days of the transfusion, leading to the destruction of the transfused canine red cells in a delayed haemolytic reaction. The average lifespan of the transfused canine red cells is less than 4 days. Any repeated transfusion with canine blood later than 4–6 days after the first transfusion causes anaphylaxis, which is frequently fatal.
Introduction
Best practice guidelines for blood transfusion in the feline species are well established and widely available.1–3 Despite this, xenotransfusion (the transfusion of blood from another species) of canine whole blood to cats is currently performed occasionally or routinely in some veterinary practices in several countries, including France, Italy and Australia (Caroline Véret and Séverine Tasker, personal communications). 4 Veterinary surgeons may thus encounter feline cases having received such a transfusion and may need to know the expected outcomes of this procedure. There may also be emergency situations when dealing with an anaemic feline patient where compatible feline blood is not available and where a blood transfusion is required urgently. Considering the current lack of commercial availability of a haemoglobin-based oxygen carrier solution (such as Oxyglobin) as an alternative to compatible feline blood, there may be rare, but genuine, occasions where transfusion of a cat with canine whole blood or packed red blood cells may need to be considered as a life-saving procedure.
The aim of this article is to review the evidence published in the veterinary literature about feline xenotransfusion with canine whole blood and the results that can be expected with this procedure. Other forms of xenotransfusion reported in both cats and dogs and not reviewed in this article include transfusion with a solution of polymerised bovine haemoglobin (bovine haemoglobin glutamer-200: Oxyglobin; OPK Biotech LLC) and transfusion with human albumin.
History of xenotransfusion
Xenotransfusion was common practice at the beginning of transfusion medicine. Although the first described transfusion was a successful dog-to-dog transfusion in 1665, the first reported transfusions to humans in 1667 were performed with blood from lambs, calves or dogs (Figure 1). Although some of these animal-to-human transfusions led to adverse reactions, such as severe haemoglobinuria and poor outcomes, others were reported to be successful at providing clinical benefits in anaemic patients. 5
Two physicians transfusing blood from a dog into a man. Reproduced with permission from Bibliothèque Interuniversitaire de Médecine, Paris, Scultetus J, 1671
In the 1800s, human transfusion with animal blood was commonplace, particularly during the Franco-Prussian War of 1870–1871. 5 Four studies were published about xenotransfusion in humans between 1863 and 1875, which reported favourable outcomes in a surprisingly large number of cases. 5 In a series of 154 cases reported in 1863, a French physiologist reported 64 ‘cures’, 20 improvements, 43 unchanged cases, one doubtful outcome and 26 deaths. 5 However, in the late 1800s it was shown that red blood cells from most domestic animals were haemolysed in human blood because of the presence of naturally-occurring antibodies against animal red blood cell antigens — explaining the occurrence of acute haemolytic reactions. 5 It was also shown that titres of these naturally-occurring antibodies increased after contact with the antigens (immunisation), explaining the occurrence of more severe reactions with repeated xenotransfusions. 5 Following these discoveries, human xenotransfusion was practically abandoned and the discovery of human blood groups in 1900 paved the way for the development of intraspecies human transfusion medicine. 5 Veterinarians followed this trend and developed intraspecies transfusions for animals; blood groups were defined in domestic species in the 1950s. 6 Feline blood types in particular were described in 1950. 7 However, the feline species has always been considered to present particular problems for transfusion medicine. The small size of cat blood donors makes blood collection technically more difficult than in other species, and sedation is frequently required for blood donation. Possibly because of these reasons and despite interspecies transfusions being abandoned in all other species since the early 1900s, reports can be found, mostly from the late 1960s, about the effects of canine whole blood transfusions to cats.4,8–11
Review of published studies and case reports in cats
First study (1962)
A study published in 1962 reported the transfusion of 22 cats with canine whole blood. 8 Pre-transfusion major compatibility tests were performed, including:
A slide agglutination test, which involved mixing 0.06 ml canine (donor) whole blood with 0.06 ml feline (recipient) plasma and 0.24 ml saline on a glass slide, then examining the slide for macroscopic agglutination for 5 mins;
An in vitro haemolysis test, which involved mixing 2 ml canine (donor) whole blood with 2 ml feline (recipient) whole blood, incubating the tube for 1 h at room temperature, then examining the supernatant for haemolysis.
No signs of incompatibilities were detected on the pre-transfusion compatibility tests (no slide agglutination or in vitro haemolysis detected). The cats were then administered 5–50 ml of canine whole blood intravenously, at a rate of 2–3 ml/min. No clinical signs of transfusion reaction were noticed during the transfusion or the following days (Table 1). The same compatibility tests were repeated daily post-transfusion. Slide agglutination of canine red cells in the feline recipient’s plasma developed in all but one case between the fourth and seventh day post-transfusion. This was consistent with the production of new antibodies against the canine red cells by the transfused cats; in the other case, the slide agglutination only became positive 12 days after the transfusion. In all but one case, in vitro haemolysis of the canine red cells became evident after 14–21 days; in the other case, haemolysis of the canine red cells was present earlier (after 7 days).
Summary of results of the 1962 study, reproduced from the original article by Hessler et al 8
Stress was characterised by anorexia, lethargy and discomfort on movement
In this case, slide agglutination of canine red blood cells in the cat’s plasma was negative immediately prior to the second transfusion although it had been positive 4 weeks previously; in vitro haemolysis of canine red blood cells in the cat’s blood was positive prior to the second transfusion
Twenty of the cats received a second canine whole blood transfusion (Table 1). Four cats were transfused within 4 days of the initial transfusion and did not develop any signs of transfusion reaction. Sixteen cats were transfused with 5–40 ml of canine whole blood 6–100 days after the initial transfusion; all but one cat developed clinical signs of anaphylaxis (dyspnoea, cyanosis, salivation, depression and coma) and the remaining cat developed haemoglobinuria. Ten cats died, nine of them within minutes-to-hours of the second transfusion. One cat survived the initial anaphylactic reaction but died 3 days later with haemoglobinaemia and severe icterus. The six other cats survived without specific treatment following their transfusion reaction. Two other cats received transfusions of 10–15 ml of canine whole blood on six consecutive days without any clinical signs of transfusion reaction. Finally, the same article mentions a transfusion of canine plasma in two cats without any clinical signs of transfusion reaction. Slide agglutination of canine red cells mixed with plasma from the recipient cats became positive after 9 days. A second transfusion of canine plasma (time not specified) caused an anaphylactic reaction in both cats; one of the cats survived. Long-term follow-up of the transfused cats was not available.
Second study (1963)
In a second study published in 1963, seven cats were transfused with 11 ml/kg of canine whole blood in which the red blood cells had been tagged with radiochromium (Cr51). 9 No pre- or post-transfusion compatibility tests were performed. No adverse reactions to transfusion were observed. The lifespan of the transfused canine red cells was 3.6 days on average (longest 5.4 days). Long-term follow-up of the transfused cats was not available.
Third study (1968)
A third study, published in 1968, reported the experimental transfusion of four cats with canine whole blood. 10 Pre-transfusion compatibility tests were performed, including:
A major compatibility test, which involved mixing two drops of washed canine (donor) red blood cells (5% suspension of red cells in 0.9% NaCl) with two drops of feline (recipient) serum;
A minor compatibility test, which was performed by mixing two drops of washed feline (recipient) red blood cells (5% suspension of red cells in 0.9% NaCl) with two drops of canine (donor) serum.
The tubes were then incubated for 30 mins at room temperature. The tubes were checked for macroscopic agglutination; if no obvious agglutination was observed in the tube, one drop was placed on a glass slide and examined for evidence of microscopic agglutination. The tubes were also centrifuged and the supernatant was examined for haemolysis. The major compatibility tests showed no in vitro haemolysis or agglutination of canine red cells with feline serum; however, red cell agglutination developed on two occasions when feline red cells were mixed with canine serum (minor compatibility test). Four cats were then transfused with 10–40 ml of canine whole blood; no clinical signs of transfusion reaction were seen during the transfusion or the following days. Subsequent compatibility tests (by the same methods) showed in vitro agglutination and haemolysis of the canine donor red cells developing 6–7 days after the transfusion. One cat received a second canine whole blood transfusion (10 ml) 4 days after the first transfusion, and one cat received two more canine whole blood transfusions (10 ml each) 1 and 2 days after the first transfusion; these cats did not develop any clinical signs of transfusion reaction. One cat received a second canine whole blood transfusion (10 ml) 7 days after the first transfusion and died a few hours after the second transfusion. Long-term follow-up of the transfused cats was not available. The same study also reported the transfusion of canine whole blood in 20 clinical feline cases, most of them suffering from severe anaemia following trauma or surgery. No compatibility tests were performed before or after the transfusions in the clinical cases. The amount of canine blood transfused varied from 5 ml to 30 ml. Fifteen cats received a single transfusion and five cats received two transfusions, the second transfusion being within 2 days of the first one. Rapid improvement in clinical signs was reported following transfusion in 18 cases; no improvement occurred in the other two cases. Mild transfusion reactions reported included tachypnoea in two cases (both during the transfusion) and hyperthermia in two cases (one during the transfusion, the other one the day following the transfusion). No severe transfusion reactions were observed. Fifteen cats survived the initial hospitalisation and transfusion period; five cats died during the transfusion or in the following days, most likely from their underlying disease.
Fourth study (1969)
A fourth study, published in 1969, reported the transfusion of eight cats with canine whole blood (amounts not specified). 11 Pre-transfusion major compatibility tests were performed, including:
A slide agglutination test, which involved mixing 0.05 ml washed canine (donor) red cells (5% suspension of red cells in 0.9% NaCl) with 0.10 ml feline (recipient) serum, then examining the slide for macroscopic agglutination;
An in vitro haemolysis test, which involved mixing three drops of washed canine (donor) red blood cells (2% suspension of red cells in 0.9% NaCl) with three drops of feline (recipient) serum, incubating for 20 mins at room temperature, then examining the tube for evidence of macroscopic red cell agglutination, and examining the supernatant for haemolysis following centrifugation.
No signs of incompatibility were detected on the pre-transfusion compatibility tests. No clinical signs of transfusion reaction were observed during the transfusion or in the following days. When the compatibility tests were repeated post-transfusion, agglutination of the canine red cells in the feline recipient’s serum was noticed from the sixth day post-transfusion in all cases. Cats who received additional canine whole blood transfusions within 6 days of the initial transfusion did not experience transfusion reactions or adverse effects (number of cats receiving repeat transfusions and number of transfusions per cat not specified), but all cats transfused with canine whole blood 7 days or more after the first canine blood transfusion died rapidly (number of cats not specified). Three cats were treated with very high doses of cyclophosphamide (21 mg/kg once daily intravenously for 7 days) in an attempt to induce immunosuppression and possible tolerance of repeated canine whole blood transfusions later than 7 days after the first transfusion, but this failed to prevent death at the second transfusion in all three cats.
Case report (2004)
The only recent case report of canine whole blood transfusion to a cat was presented at a conference in 2004 in Australia. 4 A cat of blood type B was admitted to a referral centre with a severe non-regenerative anaemia. No donor cat of blood type B was available at the time and bovine haemoglobin glutamer-200 (Oxyglobin) was not available in Australia. The cat was transfused with blood from a Labrador as a last resort. Major and minor cross-match tests were performed prior to the transfusion, with no incompatibility reaction identified. A 1 ml test dose of canine whole blood was administered intravenously to the cat, with no adverse transfusion reaction detected clinically. Following this, a total of 130 ml canine whole blood was administered to the cat over a 48h period via small intravenous boluses. The cat’s demeanour improved and no adverse effects from the transfusion were observed. Its packed cell volume improved to a level considered safer for general anaesthesia (17%). Further investigation led to a diagnosis of erythroid leukaemia. 4 The cat was euthanased over a week later; mild icterus had developed at that time, which was considered likely to be secondary to the transfusion (Richard Gowan, personal communication). The author acknowledged that canine blood transfusion to a cat was by no means the ideal treatment or recommended as best practice, but concluded that it may be useful in an emergency situation with no compatible feline blood or haemoglobin-based oxygen carrier solution available, to allow further diagnostic procedures to be performed.
Summary and discussion
Based on a limited number of cases reported in the veterinary literature (62 cats in total, Table 2), with most publications dating from the 1960s, cats do not appear to have primary, naturally-occurring antibodies against canine red blood cell antigens.4,8–11 No incompatibility was detected in reported cases on major pre-transfusion compatibility tests (slide agglutination or in vitro haemolysis tests).4,8,10,11 Occasional incompatibilities were detected on minor pre-transfusion compatibility testing, with red cell agglutination of recipient when mixed with donor serum 10 this may cause a degree of recipient red cell destruction by antibodies from the donor. This is unlikely to be significant clinically as the volume of donor plasma transfused is usually small and becomes markedly diluted in the recipient. 12 However, transfusion of large amounts of canine whole blood containing antibodies against the recipient’s red blood cells may cause significant haemolysis of the recipient’s remaining red blood cells, worsening a pre-existent anaemia. Transfusion of major and minor cross-match compatible whole blood is thus recommended. A minor cross-match incompatibility is unlikely to be clinically significant if packed red blood cells are transfused, rather than whole blood.
Summary of results of all published studies
RBC = red blood cell
No severe acute adverse reactions have been reported in the literature for cats receiving a single transfusion with canine blood.4,8–11 Mild transfusion reactions were reported occasionally (5 cats) and included tachypnoea and mild pyrexia during the transfusion or the following 24 hours, 10 and icterus in the week following transfusion (Richard Gowan, personal communication). However, the studies reviewed confirmed that antibodies against canine red blood cells are produced within 4–7 days of the transfusion, as evidenced by post-transfusion positive slide agglutination and in vitro haemolysis tests.8,10,11 This will lead in vivo to the rapid destruction of the transfused canine red blood cells in a delayed haemolytic reaction. The lifespan of the transfused canine red blood cells is less than 4 days, 9 in contrast to a lifespan of 30 days for compatible feline red blood cells. 13 Any repeated transfusion with canine blood later than 6 days after the first transfusion causes anaphylaxis (reported in over 18 cats), which is frequently fatal (more than 66% of reported cases died).
In delayed haemolytic transfusion reactions, the newly-formed antibodies adhere to the transfused red cells, which are prematurely removed from the circulation and undergo extravascular haemolysis. Haemoglobinuria does not tend to occur. 14 The clinical signs, including fever and sometimes icterus, are usually mild and may be unnoticed. 14 This may explain why such signs were rarely reported in the reviewed studies after a single transfusion of canine whole blood to cats. A sudden decrease in haematocrit is, however, to be expected within 4 days of the transfusion with the destruction of the transfused red blood cells (while compatible feline blood cells have a lifespan of 30 days). In anaemic patients this will lead to relapse of clinically significant anaemia unless the cat has developed a significant red cell regenerative response in the meantime. 14 Specific therapy for delayed haemolytic transfusion reactions is generally not indicated, but further transfusions and supportive treatment may be required if the patient becomes severely anaemic again. 14
Conclusions
Transfusion of cats with canine whole blood or packed red blood cells is not recommended as a routine procedure as it is much less beneficial than transfusion with matched feline whole blood or packed red blood cells. Transfusion of a cat with canine blood would be helpful in the very short term only because of the expected delayed haemolytic reaction. The delayed haemolytic reaction, although usually mild, may be deleterious for the transfused cat. Finally, we cannot exclude the possibility of severe acute reactions not described so far.
Although transfusion of cats with canine whole blood or packed red blood cells can in no way be considered ‘best practice’, it could, however, be considered in exceptional and genuine emergency situations if the anaemic cat has never received such a transfusion previously, if blood from a compatible feline donor cannot be obtained and if a haemoglobin-based oxygen carrier solution is not available. Major and minor cross-match tests should always be performed prior to the blood transfusion. In such emergency cases, transfusion of canine blood may allow short-term stabilisation of the anaemic cat prior to anaesthesia or diagnostic procedures, or prior to obtaining compatible feline blood. Such a transfusion may also possibly stabilise a cat with a regenerative anaemia until adequate bone marrow red cell regeneration develops. Any additional transfusion with canine whole blood or packed red blood cells later than 4–6 days after the first transfusion is expected to cause severe, frequently life-threatening, anaphylaxis and is absolutely contra-indicated.
Footnotes
Acknowledgements
The authors thank Dr Séverine Tasker for her review of this article.
Funding
This review received no grant from any funding agency in the public, commercial or not-for-profit sectors.
Conflict of interest
The authors do not have any potential conflicts of interest to declare.