A dual-center retrospective evaluation of 204 blood or plasma transfusions in 169 camelids

Abstract

Background

Transfusions in camelid species are performed without evidence-based guidelines. Safe and recommended practices for administering blood products with maximal efficacy and minimal risk of reactions are needed.

Hypothesis/Objectives

To describe the indications for, methods of, and outcomes associated with transfusions in camelids and to identify risk factors for transfusion reactions (TRs) and death.

Animals

Two hundred four transfusions performed in 169 camelids at 2 referral hospitals.

Methods

A dual-center retrospective review of medical records from 2010 to 2024. Signalment, indication for transfusion, transfusion history, administration of premedication, presence of TRs, and survival to discharge were reviewed. Dose and rate of product administration were calculated. Data were described and analyzed with a generalized linear model.

Results

In less than 1-month-old crias, the most common indication for plasma transfusion was management of failure of transfer of passive immunity. The overall TR rate was 12%, and presence of TRs resulted in a lower probability of survival to discharge (54.6%; 95%CI, 34.0%-73.6% vs 76.5%; 95%CI, 69.5%-82.3%, respectively; P = .033). There was no difference in probability of a TR with respect to administration of premedication, rate of transfusion administration, or previous transfusions (P ≥ .06). Changes to vital signs were the most common findings suggesting a TR.

Conclusions and Clinical Importance

Blood products can fulfill many therapeutic needs in the treatment of camelid species with a reasonable expectation of safety. A history of prior transfusions does not appear to significantly affect the future risk of a TR.

Introduction

Transfusion medicine is a research area of emerging interest in veterinary medicine. New data are rapidly becoming available that document risks and outcomes of transfusions as they relate to different species, storage lesions, type of blood product administered, use of premedication, and other factors.^1-13 It is unclear, however, how much of this information can be extrapolated to camelid species, given their unique blood types, red blood cell morphology, and immunologic responses. Several unique considerations exist for camelids regarding the need for pre-transfusion cross-matching, risk factors for transfusion reactions (TR), and risk vs benefit analysis of plasma transfusions for amelioration of failure of transfer of passive immunity (FTPI). Pre-transfusion compatibility testing is often recommended for small animals^1,5,9,14,15 and horses,^6,16-19 particularly for animals which have had a prior transfusion. Yet, anecdotal evidence in livestock species suggests that routine agglutination cross-matching might be of little utility.^20,21 Studies have investigated transfusion medicine in livestock species and horses and found TR rates ranging from 8.7% to 16%.^4,6,7,12 In addition, the intravenous administration of plasma within the first several days to weeks of life to artificially achieve transfer of immunoglobulins is relatively unique to large animal species. Plasma transfusion is routinely performed in foals, calves, and crias, and equine, bovine, and llama plasma products are commercially available. A final unique consideration relates to the routine administration of predominantly llama (Lama glama) plasma to other camelid species including camels and alpacas (Lama pacos), despite xenotransfusion often being considered a last resort in non-camelid species.

In large animals, important logistical differences in blood product acquisition, cross-matching, and administration limit conclusions that can be drawn from small animal research. Though some preliminary studies have reviewed TRs in camelid species,^7,22 a more comprehensive assessment of indications for transfusion, risk factors for TRs, and methods of blood product administration is lacking. Some general recommendations are available in textbooks or review articles,^21,23 but evidence-based guidelines for transfusions in camelids are not currently available. Despite this, whole blood and plasma transfusions are commonly performed, especially at referral care centers such as university veterinary teaching hospitals. Therefore, there is a need for evidence-based findings to influence the creation of best practices for camelid transfusion medicine.

The objective of this retrospective study was to describe the indications for, methods of, and outcomes associated with blood product transfusions in camelids. A secondary objective was to identify camelid- and transfusion-related risk factors for TRs and non-survival.

Materials and methods

Medical records from the Kansas State University Veterinary Health Center (KSU) and the Colorado State University Veterinary Teaching Hospital (CSU) were searched for billing codes pertaining to purchase of blood or plasma products, or to administration of a transfusion in a camelid species (llama, alpaca, guanaco, vicuña, and camel). The date range for the search was from January 1, 2010 through July 31, 2024. Animals were included if they were of a camelidae species, had documented evidence of having received any quantity of a blood product, and had a known outcome.

Data points extracted from the records included: signalment including age at hospital admission, sex, and species; presenting complaint; history of prior transfusion; and body weight (BW). For further analysis, each hospital visit was further subdivided into age groups based on camelid age at time of presentation: 1 (≤48-hours [hr]-old), 2 (>48-hours-old and ≤ 1-month-old), 3 (>1-month-old and < 1-year-old), and 4 (≥1-year-old). Physical exam findings were also recorded. The final diagnosis listed in the medical record was recorded. In cases of death, antemortem diagnosis was used. When available, postmortem examination findings were recorded.

Data extracted regarding transfusions included the number of transfusions administered during the visit, day of hospitalization when transfusion was performed, and indication for transfusion. Route of blood product administration and type (plasma, whole blood, and packed red blood cells [pRBC]) and source of blood products were noted. The use of premedication (defined as any nonsteroidal anti-inflammatory drug [NSAID], corticosteroid, or antihistamine) administered within 24 hr before the transfusion, noted TRs and subsequent interventions, and duration of transfusion (minutes) were recorded.

Terms used in the study were clearly defined. A hospital visit was defined as an independent hospital admission of variable length for either in-patient or out-patient care. A transfusion was defined as administration of a single-source blood product over a single continuous period (eg, administration of plasma from a single commercial lot or administration of whole blood from a single blood donor animal). If 2 types of blood products were administered consecutively (eg, whole blood followed immediately by plasma or 2 different lots of commercial plasma administered consecutively), these were considered separate transfusions given the opportunity for multiple antigenic sources to elicit a TR. A transfusion event was a single time period of administration of one or more transfusions (eg, administering whole blood and plasma immediately consecutively). Subsequent administration of an additional blood product was considered a separate transfusion event if there was evidence of re-assessment in the interim period that justified the need for another transfusion. Lastly, a TR was defined as any change in clinical exam or pathologic data identified in the medical record that was potentially attributable to administration of a blood product.

Dosage of blood product (mL/kg BW) and overall administration rate of blood product before any noted TR (mL/kg/hr) were calculated. A history of prior blood product administration within 1 week, 3 weeks, or at any time was determined for each transfusion. Finally, short-term survival, days in hospital, and where applicable, manner of death and necropsy results were recorded. Short-term survival was defined as survival to discharge from the hospital.

Data analysis

Data were analyzed using a generalized linear model using a binary distribution with a logit link function using the GLIMMIX procedure of SAS (version 9.4; Cary, NC). The probability of TR and probability of survival was modeled by creating univariate logistic regression models to test the effect of the variable of interest. For survival analysis, the modeled data are the probability of an individual transfusion resulting in death or euthanasia. Descriptive statistics were determined using the UNIVARIATE procedure of SAS. Means for predictor variables, SE, and CIs were generated using the LSMEANS procedure of SAS. Significance was declared at P ≤ .05.

Results

In total, 119 records were identified from CSU and 55 records from KSU. Among the KSU records, 52 camelids were identified within 55 individual hospital visit records (3 camelids had 2 visits each), and a total of 68 transfusions were performed. Among the CSU records, 117 camelids were identified in 119 hospital visit records (2 camelids had 2 visits each), and a total of 136 transfusions were performed. Overall, 204 transfusions were identified among 174 unique hospital visits. Plasma was the most common blood product administered (n = 172, 84.3%) followed by whole blood (n = 29, 14.2%) and pRBC (n = 3, 1.5%). The median duration of hospitalization was 5 days (range, 1-38 days).

Signalment data

Among all unique camelids (n = 174), alpacas were the most represented (n = 141, 81%) followed by llamas (n = 23, 13%), guanacos (n = 5, 3%), and camels (n = 5, 3%). The median age was 3 days (range, newborn—24 years). When age for each hospital visit (n = 174) was further subdivided into age categories, there were 74 camelids (42.5%) in age group 1 (≤48-hr-old), 56 camelids (32.2%) in age group 2 (>48-hr-old and ≤ 1-month-old), 9 camelids (5.2%) in age group 3 (>1-month-old and < 1-year-old), and 35 camelids (20.1%) in age group 4 (≥1-year-old). Female camelids were more common (n = 100, 57.5%) compared to intact males (n = 72, 41.4%) and castrated males (n = 2, 1.1%).

Indications for transfusion

The most common indication for any type of transfusion was FTPI with or without concurrent septicemia (Table 1). Nine camelids (all crias less than 7 days old) had a sole indication for treatment of confirmed or suspected neonatal septicemia. Those crias were combined with crias (all less than 2 months old) that had an indication for treatment of FTPI (n = 136/152 transfusions in crias < 2 months old). All camelids with an indication of FTPI or septicemia were 2 months of age or younger. In 1 case, a 2-day-old alpaca cria was administered a plasma transfusion based solely on owner request.

Table 1.

Indications for 204 blood product transfusions and type of blood product administered among camelids presented to 2 referral veterinary hospitals.

Indications	Plasma (n = 172)	Whole blood (n = 29)	pRBC (n = 3)	Totals
FTPI + septicemia	136	0	0	136
Hypoproteinemia	31	0	0	31
Hemolysis	0	1	0	1
External blood loss	1	19	3	23
Anemia of unknown cause	0	9	0	9
Coagulopathy	1	0	0	1
Not noted	2	0	0	2
Owner-driven	1	0	0	1

Abbreviations: FTPI = failure of transfer of passive immunity; pRBC = packed red blood cells.

External blood loss (n = 23/204 transfusions) was treated with whole blood (n = 19), pRBC (n = 3), and plasma (n = 1). Causes of external blood loss included primary gastrointestinal parasitism, reproductive complications, severe hematuria, compartment 3 ulceration, surgical blood loss, and external hemorrhage secondary to suspected coagulopathy. In 2 cases, indications for transfusion could not be identified based on review of the medical record.

Survival

Among 174 hospital visits, overall survival to discharge was 73.6% (n = 128; Table 2). Twenty camelids died while 26 were euthanized. There was a significant difference in the probability of survival between age groups (P = .028). Camelids in age group 1 had a greater probability of survival (80.5%; 95%CI, 70.4%-87.7%) compared to camelids in age group 4 (57.5%; 95%CI, 41.9%-71.8%; P = .046). Probability of survival was lower for camelids experiencing a TR (54.5%; 95%CI, 34.0%-73.5%) compared to those not experiencing a TR (76.5%; 95%CI, 69.5%-82.3%; P = .033). Other signalment factors (species, sex) and transfusion factors (history of prior transfusion, type of blood product, administration of premedication, blood product dose, and rate of fluid administration) did not significantly affect probability of survival (Table 3). Euthanasia was performed for a variety of reasons including owner financial restrictions, poor prognosis associated with disease, lack of improvement with therapy, and in response to ongoing severe TRs.

Table 2.

Survival outcomes (to hospital discharge) by age group for 174 hospital visits of camelids presented to 2 referral veterinary hospitals and receiving a blood product transfusion. Data are presented as frequency (percent).

Age group	Survival (n = 128) (%)	Non-survival (n = 46) (%)	Total (n = 174)
1 (≤48-hr-old)	59 (79.7)	15 (20.3)	74
2 (>48-hr-old and ≤ 1-month-old)	43 (76.8)	13 (23.2)	56
3 (>1-month-old and < 1-year-old)	5 (55.6)	4 (44.4)	9
4 (≥1-year-old)	21 (60.0)	14 (40.0)	35

Percentages are within row.

Table 3.

Association of signalment and transfusion-related factors with probability of transfusion reaction and probability of survival among camelids receiving 204 transfusions.

Factor	Probability of TR (P)	Probability of survival (P)
Animal factors
Age	.93	.028
Species	.56	.42
Sex	.36	.12
Transfusion factors
Previous transfusion within 1 week	.92	.58
Previous transfusion within 3 weeks	.64	.74
Previous transfusion at any time	.85	.78
Type of blood product	.51	.95
Administration of premedication	.62	.47
Blood product dose (mL/kg)	.82	.069
Rate of fluid administration (mL/kg/hr)	.063	.60
Occurrence of TR (yes/no)	N/A	.033

Bolded values indicate significance (P < .05).

Abbreviations: N/A = not applicable; TR = transfusion reaction.

Transfusion data

Source of blood products

Of 204 administered blood products, 172 were plasma products, 3 were pRBC, and 29 were whole blood. Sources of blood products noted in the records included commercial llama plasma, a donor camelid from the same owner, and donor llamas or alpacas from the university blood donor herds. The exact source of blood product (commercial brand or identity of donor animal) was only documented in 55% of all transfusions. Biochemical characteristics and PCV of transfused blood were rarely recorded. There were no instances of administration of stored RBC products (all blood was collected from donors at the time of transfusion). There were frequent instances of xenotransfusion, particularly of llama-sourced blood products to other species (Table 4).

Table 4.

Species of origin of transfused blood products administered to camelids presented to 2 referral veterinary hospitals in a retrospective study of 204 transfusions. Data are presented as frequency (percent).

	Origin species of blood products
Recipient species	Llama	Alpaca	Camel	Not specified	Total
Alpaca, n (%)	102 (65%)	8 (5%)	0 (0)	48 (30%)	158
Llama, n (%)	18 (55%)	9 (27%)	0 (0)	6 (18%)	33
Guanaco, n (%)	3 (43%)	3 (43%)	0 (0)	1 (14%)	7
Camel, n (%)	4 (66%)	0 (0)	1 (17%)	1 (17%)	6
Total	127	20	1	56	204

Percentages are within row.

Dosage of plasma product

Mean, median, and ranges for administered plasma dosage were determined for plasma transfusions. In less than 48-hr-old neonates (age group 1), the median and mean dosages of administered plasma transfusions were equivalent (36 mL/kg BW) with a range of 8-62 mL/kg BW. For crias in age group 2, median and mean dosages were also equivalent (35 mL/kg BW) with a range of 16-57 mL/kg BW. Median and mean dosage of administered plasma for age group 3 was 20 and 21 mL/kg BW, respectively, with a range of 12-36 mL/kg BW. Median and mean dosage of plasma for age group 4 was 8 and 10 mL/kg with a range of 3-21 mL/kg BW.

Route of administration

Four transfusions were administered via the intraperitoneal route. These were all in less than 48-hr-old alpaca crias with transfusion indications of treatment of FTPI. Two of the 4 crias were also diagnosed with dysmaturity. Where noted, transfusion volume represented 35-40 mL/kg BW, and no TRs were noted in the records. All 4 crias survived to discharge. Route of blood product administration relative to risk of TR was not evaluated statistically due to the few number of cases undergoing intraperitoneal administration. All other transfusions were administered intravenously.

Transfusion reactions

Twenty-six reactions were recorded in 24 transfusions (24/204 transfusions; 12%), and 2 camelids experienced 2 reactions each (Table 5). Among the 24 transfusions, 23 individual camelids were represented, and 11 did not survive to discharge (11/23; 48%). Three of the 24 (3/24, 13%) transfusions during which a reaction occurred were proceded by a prior transfusion. Within each blood product type, TRs were most frequent for whole blood (n = 5, 17% of all whole blood transfusions) followed by plasma (n = 19, 11% of all plasma transfusions). No TRs were noted for pRBC transfusions. The most frequent TR types were changes to vital signs (n = 20/26 transfusions, 77%) compared to pre-transfusion baseline values including heart rate (increased rate); respiratory rate, effort, or pattern; and rectal temperature. A numerically greater number of animals that experienced a change in respiratory function did not survive when compared with animals experiencing other signs of TRs. In addition to increased respiratory rate, other alterations in respiratory function included transient auscultation of crackles, increased respiratory effort including open-mouth breathing, and intermittent cough. Neonatal crias (less than 1 month old) experienced 83% (5/6 transfusions) of all respiratory TRs. All instances of shaking or trembling were transient and resolved without intervention or change in transfusion rate. A 24-hr-old cria experienced suspected systemic anaphylaxis within 40 min of starting a plasma transfusion. Clinical signs included panting and frothy epistaxis that quickly led to death. The diagnosis of systemic anaphylaxis was strongly supported on post-mortem examination. The rate of fatal anaphylaxis was therefore 0.5% (n = 1/204 transfusions).

Table 5.

Types of transfusion reactions and survival to discharge outcomes among camelids presented to 2 referral veterinary hospitals in a retrospective study of 204 transfusions.

		Survival outcome
Type of reaction	Number of reactions (n = 26)	Survived (n)	Non-survival (n)
Increase in heart rate	6	3	3
Change in respiratory rate, effort, or auscultation	6	1	5
Increase in rectal temperature	7	6	1
Shaking/tremblinga	3	1	1
Systemic anaphylaxis	1	0	1
Mentation change/onset of neurological signs	3	2	1

Survival is defined as survival to hospital discharge.

^aOne camelid experienced shaking/trembling during 2 separate transfusion events during the same hospital visit.

Risk of transfusion reactions

Twenty-nine camelids received more than 1 transfusion, either concurrent with another transfusion or at a subsequent time point. The shortest duration between transfusion events was 16 hr. The longest duration between events during a single hospital visit was 4 days. The longest duration between transfusion events at separate visits was 14 months. Risk of TR was evaluated for camelids with a history of receiving blood products within 1 week, 3 weeks, or at any time before their transfusion. Receiving a prior transfusion was not associated with risk of TR (P > .05).

Premedication was administered before 118 transfusions (118/204, 58%). An NSAID was administered in 115 cases (115/118, 97%), a corticosteroid in 2 cases (2/118, 2%), and both an NSAID and corticosteroid in 1 case (1/118, 1%). Flunixin meglumine was the most common NSAID administered (n = 112) followed by meloxicam (n = 3 transfusions). Dexamethasone was used in the 3 cases where a corticosteroid was administered (the camelid that also received an NSAID was administered flunixin meglumine). It was frequently not possible to discern whether premedication was administered specifically for the purposes of the transfusion or for treatment of the underlying disease condition. No antihistamine administration was noted in any records. Administration of NSAID or corticosteroid premedication within 24 hr of starting a transfusion was not associated with less risk of experiencing a TR (P = .62).

Average rate of fluid administration adjusted for BW was available for 134 transfusions. The mean and median rates, measured before any TR occurring, were 15 and 10 mL/kg/hr, respectively. Though not statistically significant, there was a tendency for increasing rate of fluid administration to be associated with lower risk of TRs (P = .063). All other signalment (age, species, and sex) and transfusion factors (history of prior transfusion, type of blood product administered, and blood product dose) did not show statistically significant relationships to probability of TR (P > .05; Table 3).

Discussion

This study evaluated the use and outcomes of blood product transfusions in camelids at 2 university referral hospitals. Plasma, whole blood, and pRBC were administered for a variety of indications and were generally well-tolerated. The rate of TRs was comparable to that reported in another study documenting transfusions in alpacas,⁷ and TRs typically presented as changes in vital parameters. Premedication, particularly flunixin meglumine, was commonly administered.

In the present cohort of camelids, the most common indication for transfusion was treatment of FTPI with or without concurrent neonatal septicemia. As in other large animal species, plasma transfusions are used both to raise serum IgG concentrations and as adjunctive treatment of disease such as septicemia. Given the frequency of a presumptive diagnosis of septicemia combined with a common comorbidity of FTPI, it was difficult to separate these 2 indications in the present study. There were, however, crias and camel calves with isolated FTPI that were administered plasma for the sole purpose of raising serum IgG concentration. There are no controlled studies examining plasma therapy as a treatment or supportive measure for sepsis in large animal species. There is conflicting evidence on the benefits of plasma transfusion as an adjunctive treatment for sepsis in humans.²⁴ The median plasma transfusion dose administered to less than 1-month-old crias was 35 mL/kg BW which is within the range that has been recommended for treatment of FTPI (20-40 mL/kg) in neonatal ruminants²¹ but greater than that recommended in camelid crias (15-25 mL/kg).²⁵ Dose recommendations are inherently variable due to differences in IgG concentration between plasma units and the rate of consumption of IgG after transfusion if the neonate has concurrent disease conditions. In this study, all TRs that occurred in crias receiving plasma were to animals with concurrent diagnoses (septicemia, prematurity).

Transfusion-associated circulatory overload (TACO), a type of respiratory TR, might be of particular importance in large animal neonates which receive large volumes of plasma for treatment of FTPI. In an otherwise euvolemic animal, administration of this dose of fluid can lead to circulatory overload with concurrent development of pulmonary edema and respiratory compromise. A study of healthy neonatal crias administered 30 mL/kg of plasma intravenously over 90 min documented an increase in central venous pressure and decrease in functional residual capacity suggesting clinically important intravascular volume expansion.²² Though life-threatening TRs were rare in this study, administration of plasma to an otherwise healthy cria with inadequate passive transfer of immunity should be undertaken with care and include monitoring for signs of TACO. This is especially important in sick crias which might be less tolerant of fluid overload. Veterinarians using plasma for treatment of FTPI should focus on selecting a product with a high IgG concentration to limit the transfusate volume required. In situations where commercial plasma with a known IgG concentration is unavailable, the ideal donor could be a well-vaccinated castrated male or maiden female herd mate with no history of prior transfusion. This donor will have an IgG profile that most closely mirrors the infectious agents present on the farm.

Transfusion of blood products between species within the camelidae family (inclusive of the llama, alpaca, guanaco, vicuña, dromedary camel, and Bactrian camel) has been anecdotally practiced and occasionally reported.^26-28 In our study group, commercial llama plasma was administered to alpacas, llamas, guanacos, and camels. Red blood cell products were administered between llamas and alpacas, and guanacos received alpaca whole blood (Table 4). Early studies report that llamas and guanacos contain no isoagglutinins or isohemolysins²⁹ which are clinically relevant alloantibodies that can bind and induce hemolysis of either donor or recipient red blood cells. If naturally occurring, these antibodies would likely increase the rate of TRs in otherwise transfusion-naïve camelids. As in horses and ruminants, it has been found that llamas and alpacas have multiple red cell factors³⁰ which might further decrease the likelihood that any alloantibody production after a transfusion would result in a TR when another randomly selected blood product is administered. With the low rate of TRs presented here (12%) combined with little new information regarding camelidae blood types, it seems that administration of blood products between camelid species is generally safe and feasible, and this will help expand the potential donor pool.

In the current study, pre-transfusion crossmatching was only performed before 1 transfusion in a naïve animal, and crossmatching was not performed before any subsequent transfusions. Pre-transfusion crossmatching is not routinely performed as it can be costly, time-consuming, and inaccessible based on local laboratory capabilities. Routine agglutination crossmatching is unable to assess hemolytic reactions (acute or delayed hemolysis of recipient or transfused red blood cells)³¹ which are reported to be more important for ruminant and camelid species.^18,20,21 Furthermore, any type of crossmatching is incapable of detecting all types of TRs¹⁷ including non-immunologic reactions. Non-immunologic reactions can occur secondary to ex vivo factors that damage red blood cells (such as issues with storage temperature or on-going cellular metabolism in stored products), contamination of transfused products, or administration factors such as large transfusion volume leading to fluid overload or citrate toxicity. Furthermore, there is often a lack of suitable blood donors leading to situations where a life-saving transfusion is indicated regardless of ability to assess clinical compatibility beforehand. In support of the recommendation that pre-transfusion crossmatching might not be indicated, only 1 transfusion in the present study was preceded by a crossmatch procedure, and the rate of fatal anaphylaxis was 0.5% of all transfusions. In another retrospective review of South American camelid transfusions, a reaction rate of 15% was reported with no fatal outcomes despite no crossmatching being performed.⁷ Studies in other species with various blood products have reported highly variable TR rates,^{1,3,4,6,8-12,26,31,32} and it is probable that delayed reaction types or those that require laboratory evaluation for detection (no overt clinical signs) are likely to be underrecognized.

Transfusion reactions are frequently mild and of minor clinical consequence, but they can result in variable clinical presentation, timing, severity, and impact on efficacy of the transfusion.^{1-4,6,7,9,11,12,15,18,23,31,33,34} Though anaphylactic reactions are often associated with severe clinical outcomes,^6,9,31 there are a breadth of other TR types that have recently been better defined in small animal transfusion medicine.³¹ While similar adverse TR signs have been reported in horses,^4,6,12,19,34 ruminants, and camelids,^{7,18,21,23,32} a comprehensive assessment defining and categorizing TRs in large animals is currently not available.

Results of the current study identified several types of TRs. Febrile reactions are defined in small animal transfusion medicine as a body temperature of greater than 39°C (102.5°F) with an increase of 1°C (1.8°F) during or within 4 hr after conclusion of transfusion.³¹ Similar published guidelines are not available for camelid species, but an increase in rectal temperature noted in the medical record was seen in the records of 7 camelids. In all cases, the transfusion was able to be completed. Febrile reactions are typically secondary to transfused white blood cell or platelet cytokines and therefore are more common with whole blood transfusions.^31,33,34 Despite this, only 1 of 7 febrile reactions occurred in camelids receiving whole blood. Leukoreduction has shown mixed results in reducing the rate of febrile nonhemolytic reactions.^2,3,31 It is less commonly practiced in veterinary medicine due to the extra time and cost associated with purchase and use of leukoreduction filter bags, however, and was not performed prior to any transfusions in the current study. Fever can also be associated with hemolytic reactions, particularly with red blood cell transfusions, but no mention of peri- or post-transfusion hemolysis was noted in any records. This should not be taken to conclude that development of antibodies against foreign transfused cellular antigens or proteins (alloimmunization) does not occur in camelids. It is possible that hemolytic TRs might occur in camelids at a lower rate than in small animals, hemolysis could be relatively delayed by the body’s production of alloantibodies to transfused red blood cells, or that post-transfusion monitoring is insufficient to detect hemolysis. Clinically relevant alloimmunization has traditionally been thought to occur over several weeks, but new research suggests that it can occur within days.⁵ Given that alloimmunization likely occurs in camelids post-transfusion, it was surprising that a history of prior transfusion at any time point was not a risk factor for subsequent TR. This might suggest a broad array of red blood cell antigenic groups, a decreased rate of alloimmunization in camelid species, unrecognized minor TR, or an inadequate sample size to detect an effect of prior transfusion. The presence of follow-up bloodwork was also inconsistent so any accompanying acute or delayed hemolytic reactions might not have been identified. This is especially true for those animals which were discharged within 24-48 hr after completion of the transfusion and for which long-term monitoring of physical exam and bloodwork variables was not possible.

While thresholds for degree of change in temperature are established for small animal TRs, no such guidelines exist for changes to heart rate. While increased heart rate or overt tachycardia was noted in 6 transfusions, this change in vital parameter is nonspecific with regard to pathophysiology of different reaction types. In addition, excitable animals such as crias can experience physiologic tachycardia from being restrained for examination, and underlying disease state can also influence heart rate variability. Further research is required to establish how changes in heart rate can be used as an indicator of TRs in camelids. In contrast to heart rate, changes in respiratory function can represent a primary respiratory TR or be a component of more systemic dysfunction such as with an allergic reaction. Neonatal large animals being treated for FTPI with large volumes of plasma could be at increased risk for TACO, as was previously discussed. Other respiratory specific reaction types include transfusion-related acute lung injury and transfusion-associated dyspnea.³¹ Definitive etiologic evidence (such as thoracic radiographs or echocardiographic evaluation) for any of these specific reaction types was not pursued in any case, and the potential exists that respiratory signs were manifestations of other primary TR types. As for other reaction types, underlying disease processes might have contributed to alterations in respiratory function, particularly in those cases where the animal was premature or dysmature. Trembling or fasciculations and mentation change have been previously reported as possible TRs in veterinary species,^{1,4,12,18,19,23,33} but pathogenesis of these signs is not well described.

One objective of the study was to investigate factors that influence both survival to discharge after a transfusion and risk of experiencing a TR. Systematic studies examining risk factors for veterinary TRs are limited. Interestingly, no signalment factors (age, sex, and species) nor transfusion-related variables (prior transfusion, type of blood product, administration of premedication, rate of fluid administration, and dose of blood product) influenced risk of reaction, though it is important to note that this was not a controlled study designed to assess causative associations. Reaction rate was not found to be statistically greater for whole blood vs plasma transfusions (17% vs 11%, respectively). Whole blood contains additional antigens including red blood cell and platelet epitopes as well as white blood cell cytokines that make reactions more likely, but we did not find a significant difference in our study population. One explanation for this could be the low number of cases of whole blood and pRBC transfusions compared with plasma transfusions. With respect to premedication, conflicting reports exist regarding the protective utility of corticosteroids and antihistamines.^1,3 An NSAID might be preferred over a corticosteroid for camelid species due to their propensity for glucose dysregulation with the latter.^35,36 Given the breadth of TR pathophysiology and the relative lack of use of corticosteroids and antihistamines, further conclusions about use of these medications cannot be drawn. Faster rates of fluid administration tended to reduce the likelihood of TRs. A study in dogs found that slower administration rates were associated with greater risk of febrile, nonhemolytic reactions, though administration rate was calculated over the entire period of transfusion administration.⁸ Given that faster administration rates can increase the risk for some TRs, particularly TACO, it is possible that faster rates are a product of clinician choice to increase administration rate in transfusions which were proceeding without incident. Some resources suggest that transfusions in veterinary medicine should follow recommendations from human medicine to administer red blood cell products within 4 hr to minimize risk of bacterial growth,^33,37 but these recommendations have been questioned.^38,39 While an intriguing finding, these results should not be construed as fact that a more rapid rate of fluid administration is protective against TRs. Experiencing a TR was negatively associated with survival to discharge; however, death during or shortly after a transfusion might have been more influenced by underlying disease condition than by the transfusion. Younger animals, particularly those in age group 1, were more likely to survive to discharge which is likely a reflection of a treatable underlying disease process more than factors related to transfusion, though this could not be confirmed. Due to incomplete medical records, reasons for euthanasia were frequently omitted, but financial constraints could have influenced survival.

There are several limitations to the present study. As for other retrospective studies, the availability, legibility, and completeness of medical records was imperfect. There was inherent bias in differentiating TRs from underlying disease processes based on review of the medical record alone. A conservative approach to defining TRs was therefore adopted for this study, and noted abnormalities could have been incorrectly ascribed to a transfusion complication, as has been discussed elsewhere.¹² There were relatively few red blood cell transfusions which limited our ability to draw conclusions about relative transfusion risk by blood product. The specific characteristics of transfused blood products can also vary, as previously demonstrated in an equine study,⁴⁰ which introduces an additional layer of uncontrolled variability. Lastly, the impact of other types of premedication used more routinely in human and small animal veterinary medicine (antihistamines, corticosteroids) as it relates to TRs could not be assessed. Further research is warranted to determine their utility in camelid transfusion medicine.

Conclusion

The results of this dual-center retrospective study of camelids provide veterinarians information regarding the apparent safety and feasibility of blood product transfusions in camelids. Failure of transfer of passive immunity was the most common indication for any type of blood product transfusion, and larger volumes of plasma were routinely administered to neonatal crias. Overall, xenotransfusion between camelidae species was commonly performed and well-tolerated. The utility of premedication in decreasing the risk of TRs remains questionable. A history of prior transfusion might not significantly increase the risk of TRs and should not serve as a steadfast barrier to repeat transfusion if clinically warranted.

Abbreviations

BW

body weight

CSU

Colorado State University

FTPI

failure of transfer of passive immunity

hr

hour

IgG

immunoglobulin G

KSU

Kansas State University

NSAID

nonsteroidal anti-inflammatory drug

pRBC

packed red blood cells

TACO

transfusion-associated circulatory overload

TR

transfusion reaction

Conflicts of interest

The authors declare no conflicts of interest.

Funding

The authors received no specific funding for this work.

Off-label antimicrobial declaration

Any use of antimicrobials was performed historically.

Institutional animal care and use committee or other approval declaration

The hospital board at Colorado State University approved the use of medical record data for this research, as clients sign consent forms agreeing to the use of anonymized medical records for retrospective research. The hospital board at Kansas State University approved the use of medical record data for this research.

Human ethics approval declaration

The authors declare human ethics approval was not needed.