Retrospective study of canine blood xenotransfusion compared with type-matched feline blood allotransfusion to cats: indications,effectiveness,limitations and adverse effects

Abstract

Objectives

Xenotransfusion is the transfusion of blood from one species to another. With varying availability of allogenic feline blood (AFB) and in emergency conditions, circumstances occur when canine blood is transfused to cats. This study aimed to characterise the indications, effectiveness, limitations, and acute and late transfusion-related adverse effects of canine blood xenotransfusion compared with matched AFB to anaemic cats, and their survival and longer-term outcome.

Methods

This retrospective study (2013–2020) examined cats receiving canine blood xenotransfusions or AFB.

Results

The study included 311 cats (xenotransfusion [X-group], n = 105; allotransfusion [A-group], n = 206). Xenotransfusion was more frequent among cats sustaining haemorrhage than in those with haemolysis (P <0.01) or hypoproliferative anaemia (P <0.001). Financial constraints were the most common reason to elect xenotransfusion (49%). The post-transfusion mean packed cell volume was higher (P <0.001) in the X-group (22%) compared with the A-group (18%), and also higher (P <0.001) at 48–96 h post-transfusion (23% vs 18%, respectively). Transfusion-related adverse effects (TRAEs) were more frequent (P = 0.001) in the X-group (37.1%) compared with the A-group (19.4%), as were delayed haemolytic transfusion reactions (85% vs 42.5%, respectively; P <0.001). Acute transfusion reactions (ATRs) were more frequent (P <0.001) in the A-group (60%) compared with the X-group (20%). TRAEs were unassociated with survival to discharge. The survival to discharge rate of the X-group (55%) was lower (P = 0.007) than in the A-group (73%), while post-discharge survival rates to 30 days of cats surviving to discharge were 90% and 88%, respectively (P = 0.85).

Conclusions and relevance

Canine blood xenotransfusions to cats might save lives in emergency conditions when AFB is unavailable or blood typing is infeasible. The survival to discharge rate of the X-group was lower than that of the A-group. The longer-term survival rate of cats administered xenotransfusions and surviving to discharge from the hospital was good.

Keywords

Transfusion anaemia packed red blood cells blood crossmatching transfusion-related adverse effects

Introduction

Xenotransfusion is the transfusion of blood from one species to another. Xenotransfusion of animal blood to humans has been documented since the 17th century, with both positive and fatal consequences.^1
–4 In the late 1800s, it was revealed that animal red blood cells (RBCs) were haemolysed when transfused to humans, due to the presence of naturally occurring anti-RBC antibodies.¹ This, along with the discovery of human blood groups in 1900, paved the way to developing human allotransfusion medicine.¹

Reports of xenotransfusion in modern veterinary medicine of canine whole blood (WB) transfusion to cats exist, mainly from the late 1960s.^2,5
-8 Some cross-species blood product transfusion was, and still is, reported in veterinary medicine (eg, transfusion of bovine haemoglobin-based oxygen carriers molecules [HBOCs] and human albumin to dogs and cats).^2,9,10 Despite set guidelines for blood product transfusions in cats, and the relative availability of allogenic feline blood,^11
–13 when typing or matching donor and recipient cats is impossible, when matched blood is unavailable or when financial constraints limit transfusing matched feline blood, canine blood xenotransfusion to cats becomes relevant, warranting investigation of its effectiveness and adverse effects.

The AB blood system is the major feline blood antigen system, including, in order of prevalence, blood type phenotypes A, B and AB (also termed C).¹⁴ Their prevalence varies between breeds and geographical areas.¹⁴ The additional blood group system Mik has two phenotypes, Mik(+) and Mik(–). Mik typing is not feasible, given the unavailability of reagents, warranting donor-recipient crossmatching.¹⁵ Feline blood typing before administering blood products minimises acute blood transfusion-associated haemolysis. In 70% of cats with blood type A, anti-B-type haemagglutinin and haemolysin titres are low, but in the remaining 30%, their titres are high and they might sustain severe haemolysis when transfused type-B RBCs.¹⁶ Conversely, practically all cats with blood type B have high anti-A-type haemagglutinin and haemolysin titres, and when transfused as little as 1 ml of type-A blood, acute, potentially fatal transfusion reactions and anaphylactic shock might occur.^16
–18 Type-AB cats do not express antibodies against either A- or B-type RBCs. Their RBCs might induce an acute haemolytic transfusion reaction if transfused to cats with blood types A or B. Cats with blood type AB should receive AB-type RBCs, and when unavailable, A-type RBCs, washed, to avoid minor post-transfusion reactions.¹⁴

Transfusion-related adverse effects (TRAEs) include immunological (ie, non-haemolytic fever, urticaria, haemolysis, immunosuppression and thrombocytopenia) and non-immunological (ie, infective agent transmission, sepsis, hypocalcaemia, hyperkalaemia and circulatory overload) reactions.^19
–21 Identifying TRAEs can be challenging, in the face of concurrent underlying diseases characterised by clinical signs potentially resembling those of TRAE.

Although case reports of canine blood xenotransfusions to cats have suggested that cats do not naturally express anti-canine RBC antibodies,^{2,5
–8,22
–28} recent crossmatch studies reported a high prevalence of significant feline–canine blood incompatibilities, indicating that naturally occurring antibodies potentially do exist in cats and vice versa.^26,29,30 Nevertheless, no severe acute adverse reactions were described in cats receiving single canine blood transfusions, and most such cats were reported to have improved clinically.^{6
–8,22
–29} Anti-canine RBC antibodies appear within 4–7 days after xenotransfusion. Additional canine RBC transfusions to cats, more than 4–6 days after the first, are therefore expected to induce severe, potentially life-threatening anaphylaxis, and are contraindicated.²

This retrospective study examined a relatively large cohort of anaemic cats receiving xenotransfusions of canine WB or packed RBCs (pRBCs), comparing it with a group of anaemic cats administered matched feline blood. The aim of the present study was to characterise the clinical situations necessitating xenotransfusion, occurrence of acute and late TRAEs, and the survival to discharge and the survival to 30 days post discharge of the cats that were discharged alive.

Materials and methods

Selection of cats, data collection and definitions

The medical record database of the Hebrew University Veterinary Teaching Hospital (HUVTH) (January 2013 to November 2021) was retrospectively reviewed for cats transfused with WB or pRBC. Cats administered canine blood components were included in the study group. The control group included cats receiving only compatible feline blood. Cats were excluded if transfused only during cardiopulmonary arrest (CPA), if cardiopulmonary resuscitation (CPR) was unsuccessful.

Data collected from the medical records included the signalment, body weight (BW), body condition score (BCS),³¹ chief complaint, feline AB blood type, aetiology of anaemia, the main reason for selecting xenotransfusion (ie, financial constraints, unavailable matched feline blood, critical condition precluding typing or crossmatching, and haemolysis of recipient’s blood), cost of xenotransfusion, pre- and post-transfusion mental status, heart rate (HR), respiratory rate (RR), rectal temperature (RT), packed cell volume (PCV), total plasma protein (TPP) and serum creatinine (sCr), length of hospitalisation, survival to discharge, in-hospital death or euthanasia, and the survival to 30 days post discharge of the cats that were discharged alive.

The aetiology of anaemia was categorised as haemorrhage (eg, trauma, surgical bleeding or flea infestation), haemolysis (eg, immune-mediated haemolytic anaemia [IMHA], haemoplasmosis or Heinz-body anaemia) and decreased erythropoiesis (eg, chronic kidney disease, inflammation or neoplasia). Owing to the fact that in some cats, several concurrent aetiologies of anaemia were diagnosed, for the purpose of analysis, the aetiology deemed primary was selected.

The mental status at presentation was defined as follows: (1) bright, alert and responsive (BAR); (2) quiet, alert and responsive, or depressed (QAR); and (3) stupor, coma or showing agonal breathing.

The volume of standard feline pRBC and WB units were approximately 25 ml and 40 ml, respectively. The canine WB and pRBC volume administered was determined based on documentation in the medical records. The transfused blood volume was also calculated in ml/kg BW. The administration of other blood products (eg, fresh frozen plasma [FFP], allotransfusion or xenotransfusion) before or after xenotransfusion was also documented.

Cats receiving blood transfusions were monitored in the intensive care unit pre transfusion and at 15 mins and hourly during transfusion, including their RT, HR, RR and occurrence of type-1 hypersensitivity reaction signs (eg, pruritus, urticaria or erythema), behavioural changes, hypersalivation and vomiting.^19,32 Adverse reactions occurring ⩽24 h post transfusion were considered acute transfusion reactions (ATRs). Fever was defined when the RT increased by >1.1°C (2°F) during transfusion or within the following 24 h. As fever in these cats was transient and self-limiting, and these cats were stable, this fever was deemed a febrile, non-haemolytic transfusion reaction (FNHTR).

Transfusion-associated dyspnoea (TAD) was defined as an acute respiratory distress, unrelated to the primary disease diagnosed, occurring during transfusion or within the following 24 h. This category was defined to identify respiratory transfusion reactions that could not be immediately classified as transfusion-related acute lung injury (TRALI) or transfusion-associated circulatory overload (TACO).²¹ Haemolysis occurring >24 h post transfusion was defined as delayed haemolytic transfusion reaction (DHTR),²¹ diagnosed in cats demonstrating icteric or haemolytic serum or plasma, pigmenturia or icterus, that had not been observed pre transfusion. Pigmenturia might be due to bilirubinuria, myoglobinuria, haemoglobinuria or true haematuria.³³ Pigmenturia was defined in this study when the colour of urine was mentioned as abnormal by the attending clinicians in the medical record, including terms such as ‘bloody urine’, ‘red urine’, ‘amber-coloured urine’, ‘dark urine’ or similar descriptions. Owing to the retrospective nature of this study, and with financial constraints that often limited laboratory testing, urinalysis was more often not carried out post transfusion. Therefore, pigmenturia was used as an inclusive ‘broad’ term.

Laboratory tests

The PCV was measured by centrifuging WB in heparinised capillary tubes. TPP was measured by refractometry (Atago). PCV and TPP were measured pre transfusion and at least once 0–48 h and 2–4 days post transfusion. WB collected in potassium-EDTA tubes was used for feline blood typing (Lal A+B Typing; Alveida). sCr was measured within 60 mins of collection (Cobas Integra 400 Plus or Cobas 6000; Roche; at 37°C).

Statistical analysis

The distribution pattern of quantitative variables was examined using the Shapiro–Wilk test. Quantitative variables were compared between the two groups using the Student’s t-test or Mann–Whitney U-test, as appropriate. Categorical variables were compared between the groups using the χ² or Fisher’s exact tests, as appropriate. Associations between two normally distributed quantitative variables were examined by the Pearson’s correlation test. χ² tests were used to compare proportions of categorical variables among more than two groups. Bonferroni’s correction was used to adjust the P value for multiple comparisons in post-hoc paired tests. All tests were two-tailed, and P <0.05 was considered significant. Analyses were performed using a statistical software package (SPSS version 28.0.1.0; IBM).

Results

The electronic search identified 316 cats that were administered RBC-containing blood products, of which 109 received canine blood products and 207 received matched feline blood products. Five cats (xenotransfusion, n = 4; allotransfusion, n = 1) received the transfusions after CPA and during CPR but did not survive resuscitation and were thus excluded. The study eventually included 311 cats (xenotransfusion [X=group], n = 105; allotransfusion [A-group], n = 206).

Selected demographic and clinical data at presentation and outcome parameters are summarised in Table 1. X-group cats (median age 36 months; range 1–228 months) were younger (P = 0.034) than the A-group (median age 66 months; range 1–216 months), and their body weight was lower (median 3.0 kg; range 0.25–8.8 kg vs median 3.8 kg; range 0.5–8.7 kg, respectively; P = 0.001). There were no significant group differences in sex, reproductive status, BCS and mucous membrane colour. The breed distribution differed (P = 0.001) between groups, with a higher proportion of domestic shorthair (DSH) cats in the X-group (89/105; 85%) than in the A-group (138/206; 67%). The proportion of stray cats in the X-group (37/104 cats; 36%) was higher (P <0.0001) than in the A-group (21/204 cats; 10%) (Table 1).

Table 1

Signalment, blood type, clinical parameters at presentation and survival of 311 cats administered xenotransfusion or allotransfusion (2013–2021)

Category	n*	Xenotransfusion group (n = 105)	n	Allotransfusion group (n = 206)	P value
Sex	105		206		0.95
Male [castrated]		59 (34) [37; 28%]		115 (66) [95; 72%]
Female [spayed]		46 (34) [15; 17%]		91 (66) [74; 83%]
Age (years)	89	5.0 ± 5.0	203	6.2 ± 4.5	0.034
Breed	105		206
Domestic shorthair		89 (39)		138 (61)	0.001*
Persian		7 (24)		22 (76)
British Shorthair		7 (33)		14 (67)
Domestic Longhair		0 (0)		9 (100)
Sphynx		1 (17)		5 (83)
Scottish Fold		0 (0)		4 (100)
Siamese		1 (20)		4 (80)
Himalayan		0 (0)		3 (100)
Other^†		0 (0)		6 (100)
Client-owned cats	104	67 (27)	204	183 (73)	0.0001
Stray cats	104	37 (64)	204	21 (36)	0.0001
Body weight (kg)	103	3.1 ± 1.8	205	3.8 ± 1.4	0.001
Body condition score	62	3.1 ± 1.5	109	3.2 ± 1.5	0.87
Blood type	62		206		0.003
A		33 (18)		155 (82)	0.056 (A vs AB)
B		19 (39)		30 (61)	0.001 (A vs B)
AB		10 (32)		21 (68)	0.55 (B vs AB)
Dehydration (%)	73	7.5 ± 2.0	147	7.0 ± 2.0	0.008
Mental status	101		196		0.008
Bright, alert, responsive		16 (35)		30 (65)	0.018 (A vs C)
QAR		69 (30)		157 (70)	0.57 (A vs B)
Stupor, coma or showing agonal breathing		16 (64)		9 (36)	<0.001 (B vs C)
Mucous membrane colour	96		191		0.79
Pink		6 (29)		15 (71)
Pale		88 (34)		169 (66)
Icteric		2 (25)		6 (75)
Hyperaemic		0 (0)		1 (100)
Hospitalisation period (days)	103	3.5 ± 3	205	4.4 ± 3.5	0.026
Survival to discharge	105		204
Survivors		58 (28)		149 (72)	0.002
Non-survivors		47 (47)		55 (53)	0.002
Euthanased		25 (45)		31 (55)
Died		22 (48)		24 (52)
30-day survival post discharge	30		48
Survivors		27 (39)		42 (61)	0.85
Non-survivors		3 (33)		6 (67)	0.85
Euthanased		1 (25)		3 (75)
Died		2 (40)		3 (60)

Data are n (%) or mean ± SD

Comparsion performed only for domestic shorthair cats

†

Including Burmese, Bengal, Angora, Maine Coon, Abyssinian, Oriental Shorthair (one each)

QAR = quiet, alert and responsive;

The reasons for selecting xenotransfusion (n = 104; unspecified in six [5.8%] cases) included financial constraints (51 cats; 49%), unavailable type-matched feline blood (29; 27.9%), emergency critical condition (16; 15.4%) and haemolysis occurring after allotransfusion of matched feline blood (2; 1.9%). Xenotransfusion was administered free of charge in 99/105 (84.8%) cats. Canine blood sources included remnants of pRBC units administered to dogs, staff-owned dog donors and owners’ donor dogs.

The proportions of feline blood types documented in the X-group (n = 62; 59%) and in the A-group (n = 206, 100%) (Table 1) differed (P = 0.003). In the X-group, 33/62 (53%) cats had blood type A, 19/62 (31%) cats had blood type B and 10/62 (16%) cats showed blood type AB. In the A-group, 155/206 (75%) cats had blood type A, 30/206 (15%) cats had blood type B and 21/206 (10%) cats showed blood type AB. The proportion of cats receiving xenotransfusion was lower (P = 0.001) among cats with blood type A compared with those with blood type B but was insignificantly different compared with blood type AB (P = 0.056) or when cats with blood type B were compared with those with blood type AB (P = 0.56).

The mental status at presentation (Table 1) differed (P = 0.008) between the groups. The proportion of cats administered xenotransfusion was higher among cats with mental status stupor, coma or showing agonal breathing compared with cats with mental status QAR or BAR (P <0.001 and P = 0.018, respectively), but did not differ between cats presenting mental status QAR and those in stupor, coma or showing agonal breathing compared with mental status BAR (P = 0.57).

The main mechanisms of anaemia differed (P <0.001) between the allotransfusion (n = 200; 97.1%) and xenotransfusion (n = 99; 94%) groups (Table 2). The proportion of cats administered xenotransfusion was significantly higher among cats sustaining haemorrhage compared with those with haemolysis or hypoproliferative anaemia (P <0.001 for both), with no difference between the latter two groups (P = 0.67).

Table 2

The main mechanism of anaemia and blood product transfusion in 105 cats receiving xenotransfusion and 206 cats receiving allotransfusion (2013–2021)

Parameter		Xenotransfusion group (n = 105)		Allotransfusion group (n = 206)	P value
Main mechanism of anaemia
Number of cats		99 (94)		200 (97)	<0.001
Haemorrhage		61 (49)		63 (51)	<0.001 (A vs B)
Haemolysis		22 (23)		74 (77)	0.671 (B vs C)
Decreased erythropoiesis		16 (20)		63 (80)	<0.001 (A vs C)
Blood product administered	n		n
Whole blood	105	17	206	4	0.72
Volume/cat (ml)	15	45 ± 44	4	40 ± 0	0.66
Volume/body weight (ml)	15	19 ± 6	4	11 ± 1	0.019
Packed red blood cells		88		202	0.25
Volume/cat (ml)	75	34.5 ± 26.0	202	27.0 ± 7.0	<0.001
Volume/body weight (ml)	75	11 ± 4	201	8.5 ± 6	0.001
Additional blood products administered post transfusion^§	105	23 (22)	206	61 (30)	0.15
Feline packed RBCs (ml/cat)	13	28 ± 20	57	28 ± 8	0.99
Canine packed RBCs (ml/cat)	10	50 ± 70	0	0 ± 0
Feline FFP (ml/cat)	8	38 ± 17	10	38 ± 13	0.99

Data are n (%) or mean ± SD

Administered after the first blood transfusion

FFP = fresh frozen plasma; RBCs = red blood cells

In the X-group, 88 (83.8%) cats received canine pRBC, while 17 (16.2%) received canine WB. In the A-group, 202 (98.1%) cats received feline pRBC while 4 (1.9%) received feline WB. The total volume, pRBC volume/kg BW and WB volume/kg BW administered were higher in the X-group (P <0.001, P <0.001 and P = 0.019, respectively) (Table 2). Additional blood products were administered to 23 (21.9%) cats in the X-group, including repeated canine pRBC within 3 days of the first transfusion (10 cats) and allotransfusion (13 cats), as well as to 61 (29.6%) cats in the A-group (Table 2).

Pre- and post-transfusion clinical and laboratory variables are summarised in Table 3. The A-group pre-transfusion HR and RT were higher (P <0.001 for both) than in the X-group. There was no significant group difference in the pre-transfusion PCV. The PCV at 0–48 h and 48–96 h post transfusion, and the difference between post-transfusion (0–48 h) and pre-transfusion PCVs were higher (P <0.001 for all) in the X-group compared with the A-group.

Table 3

Pre- and post-transfusion vital signs and laboratory analytes of 105 cats administered xenotransfusion and 206 cats administered allotransfusion (years 2013–2021)

Parameter	Reference interval	Pre-transfusion values					Post-transfusion (⩽48 h) values
		Xenotransfusion		Allotransfusion		P value	Xenotransfusion		Allotransfusion		P value
		n	Mean ± SD	n	Mean ± SD	P value	n	Mean ± SD	n	Mean ± SD	P value
Rectal temperature (°C)		100	35.6 ± 2.2	197	36.9 ± 1.8	<0.001	70	36.9 ± 1.9	135	37.4 ± 3.3	0.21
Heart rate (bpm)		100	160 ± 49	200	185 ± 37.6	<0.001	76	181 ± 35	140	187 ± 26.2	0.19
Respiratory rate (breaths/min)		87	38 ± 18	189	40 ± 18	0.45	73	33 ± 15	145	35 ± 14.5	0.36
Packed cell volume (%) [l/l]	24–45[0.24–0.45]	101	11 ± 3[0.11 ± 0.03]	206	12.0 ± 3.5[0.12 ± 0.035]	0.11	83	22 ± 7[0.22 ± 0.07]	201	18 ± 5.5[0.18 ± 0.055]	<0.001
Total plasma protein (g/dl) [g/l]	5.0–7.4[50–74]	99	7 ± 1.8[70 ± 18]	202	7.1 ± 1.5[71 ± 15]	0.83	83	7.2 ± 1.7[72 ± 17]	201	7.1 ± 1.4[71 ± 14]	0.66
Creatinine (mg/dl) [µmol/l]	0.5–1.2[44.2–106.1]	86	2.2 ± 2.96[194.5 ± 261.7]	171	2.79 ± 3.1[246.7 ± 274.1]	0.12	42	2.5 ± 3.4[221.1 ± 300.6]	134	3.0 ± 3.0[228.8 ± 228.8]	0.40

Documented TRAEs (Table 4) were more frequent (P = 0.001) in the X-group (39 cats; 37.1%) compared with the A-group (40 cats; 19.4%). DHTRs were more frequent (P <0.001) among the X-group cats with TRAEs (33; 85%) compared with their corresponding cats in the A-group (17; 43%). Pre-existing haemolytic anaemia was noted in 10/17 and 9/33 cats with DHTR in the A-group and X-groups, respectively.

Table 4

Transfusion reactions recorded in 105 cats administered xenotransfusion and in 206 cats administered allotransfusion (2013–2021)

Reaction	Xenotransfusion group(n = 105)	Allotransfusion group(n = 206)	P value
All transfusion reactions	39/105 (37.1)	40/206 (19.4)	0.001
Acute transfusion reaction	8/39 (20)	24/40 (60)	<0.001
Fever	4/8 (50)	17/24 (71)	0.28
Died during transfusion	1/8 (13)	1/24 (4)	NA
Transfusion-associated dyspnoea	3/8 (38)	12/24 (50)	0.54
Vomiting	2/8 (25)	0/24 (0)	NA
Hypersalivation	1/8 (13)	0/24 (0)	NA
Delayed haemolytic transfusion	33/39 (85)	17/40 (43)	<0.001
Icterus	11/33 (33)	2/17 (12)	0.1
Pigmenturia	8/33 (24)	1/17 (6)	0.11
Haemolytic serum	5/33 (15)	1/17 (6)	0.33
Icteric serum	11/33 (33)	14/17 (82)	0.001

Data are n (%)

NA = not applicable

Cats with TRAEs in the A-group showed significantly (P <0.001) more ATRs than the corresponding cats in the X-group (24; 60% vs 8; 20%, respectively). TRAEs were not associated with death (P = 0.825). TRAEs were noted among the non-survivors in the X-group and A-group in 18/47 (38%) and 11/55 (20%) cats, respectively (P = 0.85). Two critically ill cats, one in each group, despite displaying no signs suggestive of ATR, died during blood transfusion and were therefore classified with ATR. The X-group non-survivor sustained traumatic brain injury, deteriorated neurologically and died 2 h into the xenotransfusion. The A-group non-survivor sustained a high-rise fall and fractured humerus, underwent surgery and later developed surgical site infection and septic shock. Allotransfusion was then administered. The cat died 1 h into the transfusion.

The mean hospitalisation period was shorter (P = 0.026) in the X-group (3.5 ± 3.0 days) compared with the A-group (4.4 ± 3.5 days). One cat in the X-group was excluded from this comparison as it was hospitalised for 54 days, requiring repeated haemodialysis treatments.

The survival to discharge rate was lower (P = 0.007) in the X-group (58 [55%] cats; 22 [21%] died, 25 [24%] were euthanased due to deterioration) compared with the A-group (149 [73%] cats; 24 [12%] died, 31 [15%] were euthanased due to deterioration). There was no difference in the proportion of euthanasia between the two groups (P = 0.43). The survival rates of the cats that were discharged alive from the hospital to 30 days post discharge of the X-group (available in 30/58 cats) and A-group (available in 48/149 cats) were 90% (27/30 cats) and 88% (42/48 cats), respectively (P = 0.85).

Discussion

Canine blood xenotransfusion to cats is controversial, and not recommended as a common practice.^{26,30,33
–36} Such xenotransfusion was reported in four publications in the 1960s (⩽22 cats per study),^5
–8 in seven case reports (nine cats)^22
–28 and one case series (10 cats)³⁷ between 2004 and 2022, while the latest larger-scale study included 49 cats.²⁹ To the best of our knowledge, the present study is the largest one of canine blood xenotransfusion to cats, comparing, for the first time, these cats with cats receiving allotransfusion.

It is noteworthy that financial constraints were the most common reason for choosing xenotransfusion (49%), as almost all xenotransfusions were administered at no cost, reflecting the hospital’s shelter medicine and stray cat programme activity, as the proportion of stray cats was significantly higher in the X-group. Unavailable matched feline blood, the second most common reason to choose xenotransfusion, reflected the extremely high relative prevalence of blood type B, and especially AB blood in Israel, more so among local DSH cats,³⁸ which comprised most of the X-group. Xenotransfusion might become more relevant in geographic areas and among breeds where the prevalence of blood types AB and B is high.

The significantly lower survival-to-discharge rate in the X-group compared with the A-group was indeed possibly associated with transfusion of canine blood rather than matched feline blood. Nevertheless, additional factors likely also affected survival. Pre-transfusion HR and RT were significantly lower, and mental status stupor was more frequent in the X-group compared with the A-group, likely reflecting more serious illnesses, and negatively affecting survival. Moreover, in 15% of the cases, xenotransfusion was chosen in extreme emergencies, necessitating prompt transfusion. Such cats probably sustained severe, often fatal, conditions. Lastly, financial constraints, more common in the X-group, most likely limited diagnostics and treatment, thereby negatively affecting survival. Nevertheless, the X-group cats that survived to discharge showed a 90% survival rate to 30 days post discharge from the hospital, which was similar to the corresponding cats in the A-group, suggesting that once recovered from the acute conditions that have led to the severe anaemia, their longer-term prognosis is good.

Haemorrhagic anaemia, the most prevalent anaemia in the X-group, was significantly more common than in the A-group. This possibly also accounts for electing xenotransfusion when blood matching was impractical or when type-matched feline blood was unavailable, in view of the need to provide more rapid and aggressive transfusion in face of acute illness. Conversely, hypoproliferative anaemia was significantly more common in the A-group. Hypoproliferative anaemia often accompanies chronic diseases (ie, chronic kidney disease, neoplasia and chronic inflammation).^39
–42 In most such cats, even with severe anaemia, the option of blood typing, and waiting for available type-matched feline blood, was more likely to be clinically feasible.

Interestingly, while the pre-transfusion PCV was similar in both groups, post-transfusion PCV was significantly higher in the X-group, possibly reflecting a significantly higher transfused blood volume administered in that group. This could be carried out because the canine WB and pRBC supply was available in greater volumes than feline blood. In addition, in haemolytic anaemia, more common in the A-group, post-transfusion RBC haemolysis likely persisted, contributing to the lower post-transfusion PCV of that group.

The overall occurrence of post-xenotransfusion TRAEs was significantly higher (37.1%) than post-allotransfusion TRAEs (19.4%). Surprisingly, although TRAEs are associated with an increased mortality rate in humans and animals,^32,43
–45 survival rates of both groups in our study were unassociated with the occurrence of TRAEs.

The proportion of ATRs among all TRAEs was surprisingly lower in the X-group (20%) than in the A-group (60%). Fever, a well-documented ATR in veterinary medicine,^{21,43,46
–49} might occur alongside several types of TRAE (eg, infection, haemolytic reaction and transfusion-related acute lung injury [TRALI]).²¹ When ruling out the latter, the most likely cause of post-transfusion fever is febrile, non-haemolytic transfusion reaction (FNHTR), reported in 3.7–22.9% cats after allotransfusion,^{21,43,46,49–52} with a similar occurrence in this study, vs 10–12% after xenotransfusion,^7,29 compared with only 3.8% in the present study. It is possible that the cats in the X-group suffered from more critical illness and shock, and therefore had a lower RT. As a result, fewer fever reactions might have been detected.

Other relatively common, previously reported ATRs are of a respiratory nature, including TAD, defined as developing acute respiratory distress within 24 h of the end of transfusion,²¹ reported in 0.4–7.4% of cats,^49,50,53 and similarly recorded in this study, with no significant group difference.

In this study, DHTRs were significantly more frequent post xenotransfusion (31.4%) than post allotransfusion (8.2%), in agreement with previous findings, occurring in 25/39 (64%) cats post xenotransfusion.²⁹ The lower DHTR in this study compared with the latter study was possibly affected by the relatively early discharge of cats post xenotransfusion, owing to financial constraints. Later onset of DHTR-related signs might have therefore been unreported. Nevertheless, the present cohort of cats administered xenotransfusion is much larger than in previous reports, potentially compensating for such losses to follow-up. Underlying haemolytic anaemia was present in 10/17 (59%) and 9/33 (27%) cats with DHTR in the A-group and X-group, respectively. Although these cats potentially did present with DHTR-related clinical signs, the possibility that these were actually also associated with the underlying haemolytic anaemia cannot be overlooked.

It is noteworthy that although past in vitro results were suggestive of a potentially high risk of post-xenotransfusion ATR in cats,³⁰ such perceived donor–recipient incompatibilities were not predictive of later occurrence of DHTR in vivo.²⁹ The ‘Transfusion reactions in small animals’ consensus statement does recommend donor-recipient pre-xenotransfusion crossmatching.³⁴ Nevertheless, although crossmatching was not performed in the present cohort, mostly owing to medical urgency and financial constraints, the DHTR rate was actually lower than previously reported.²⁹

Acute kidney injury (AKI) might result from DHTR-associated haemoglobinaemia and haemoglobinuria.^54–56 This renal tubular damage is considered multifactorial, possibly involving direct cellular injury by haemoglobin filtered through the glomeruli.⁵⁷ In this study, pre- and post-transfusion sCr did not differ, suggesting that AKI is not an important overt, early post-allotransfusion or post-xenotransfusion DHTR in cats. Nonetheless, additional renal injury and function marker measurements during hospitalisation, and longer serial follow-up sCr, were mostly not performed.

Canine blood xenotransfusion to cats is generally not recommended,³⁴ but has several notable advantages. First, large donor dogs can donate a much greater volume (>10-fold) than donor cats, while canine blood collection and processing are technically easier and safer for donors.^35,58 Second, canine blood products are more available than feline ones, and typically cost less.⁵⁸ Third, xenotransfusion to cats does not require blood typing. Fourth, canine blood products are devoid of feline infectious agents.⁵⁸ Conversely, the short (approximately 4 days) lifespan of transfused canine RBCs in cats, compared with allogenic feline RBCs (approximately 30 days), is a major disadvantage of canine blood xenotransfusion,^6,59 and is not a long-term solution for chronic persistent anaemia.²³ Nevertheless, xenotransfusion might save some cats by providing a time window, albeit short, allowing time for more specific therapy, time for blood typing and obtaining compatible feline blood products, when initially unavailable. Nevertheless, in this study, there were no group differences in additional blood transfusions during hospitalisation, possibly due to the larger blood volume administered in xenotransfusions compared with allotransfusions.

The present study has some limitations. First, with its retrospective design, some data were missing in the medical records, and laboratory test monitoring during and post hospitalisation varied, thereby weakening the statistical analyses, precluding disease severity scoring with group comparisons. Second, cause and effect relationships cannot be determined retrospectively, warranting future prospective studies to examine the validity of our results. Third, regarding cats with haemolytic anaemia, distinguishing primary clinical and laboratory signs of the underlying haemolytic anaemia from those of post-transfusion DHTR is difficult. In addition, the assessment for the presence of pigmenturia was mostly based on the gross appearance of the urine, rather than on a urinalysis with urine sediment analysis, and hence, its true occurrence was probably inaccurately represented by the present findings. Fourth, in 46% of the cats administered xenotransfusion, the aforementioned financial constraints likely introduced bias, by limiting further diagnostics, treatment and longer hospitalisation, and sometimes led to euthanasia. Finally, this study was conducted in a single referral veterinary teaching hospital and its results should be applied cautiously to other clinical settings.

Conclusions

This retrospective study of xenotransfusion of canine blood to cats is the largest yet and is the first to compare xenotransfusion with allotransfusion. Importantly, only 7.6% of the cats in the X-group showed ATRs, which were mostly self-limiting, requiring no further intervention. Conversely, the overall occurrence of post-xenotransfusion TRAEs was significantly higher (37.1%) than post allotransfusion (19.4%) but was similar in both groups at 30 days post discharge. Cats administered xenotransfusions had a significantly lower survival to discharge rate, but when discharged alive from the hospital, their survival to 30 days post discharge was good and comparable to that of cats receiving allotranfusion. This suggests that xenotransfusion might be a life-saving procedure in emergency situations when feline blood products are not readily available, and when serious financial constraints limit access to feline RBCs. This retrospective study adds to the growing body of evidence regarding the potential benefits and adverse effects of canine blood xenotransfusion to cats.

Footnotes

Acknowledgements

A portion of this manuscript includes some results of a DVM dissertation, submitted by Dr Amichay-Menashe, to the Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Israel. Some of the results were presented as an abstract at the 19th European Veterinary Emergency and Critical Care Congress; Ghent, Belgium, June 2022.

Accepted: 19 May 2023

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Maria Elkin

Sigal Klainbart

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