Avian Transfusion Medicine

Chapter 24
Avian Transfusion Medicine


Stephen Cital1, Angela M. Lennox2 and Andrea Goodnight3


1San Francisco Zoo, San Francisco, California, USA


2Avian and Exotic Animal Clinic of Indianapolis, Indianapolis, Indiana, USA


3CuriOdyssey Science and Wildlife Center, Oakland, California, USA


Introduction


Whole blood and component transfusion medicine is still an evolving science in many exotic species. Only recently has the practice become more widely used and researched as to its efficacy in avian species. Often the practical aspects of obtaining appropriate donors, expense, and owner willingness are limiting factors in avian transfusion medicine. This chapter will focus on our current knowledge of avian transfusion medicine derived from an extensive literature review, methods translated from mammalian transfusion practices, and the authors’ experiences.


Avian erythrocyte physiology


The mature avian red blood cell (RBC) is relatively large in comparison to mammalian RBCs. The morphology is elliptical and nucleated (Figure 24.1). RBC concentration and packed cell volume (PCV) are greatly influenced by many factors including age, sex, hormones, hypoxia, environment, and disease (Thrall 2004). RBC size varies according to species size. In healthy birds, between 1% and 5% of RBCs in varying developmental stages might be circulating. These less mature cells are usually more round, with clumped chromatin. Percentages of immature cells greater than 5% can suggest polychromasia or polychromatophylia, indicating overactive erythropoiesis, suggestive of a regenerative anemia (Martinho 2012). Erythropoiesis in post-hatched birds occurs in the bone marrow, whereas it occurs in the yolk sac and bone marrow of embryos (King and McLelland 1984).

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Figure 24.1 Avian erythrocytes are elliptical, nucleated, and relatively large compared to mammalian erythrocytes.


(Image courtesy of Kenichiro Yagi, BS, RVT, VTS (ECC, SAIM).)


The lifespan of the avian RBC is significantly less than in mammalian species, lasting only 20–45 days. This shorter lifespan might be associated with the increased metabolic rate and higher core temperature of birds. The avian RBC has an increased rate of nutrient and oxygen consumption, which might contribute to erythrocyte destruction (Rodnan et al. 1957). Male and aged birds generally have a higher PCV than female or younger birds due to androgen and thyroxin stimulation of erythropoiesis, respectively. In contrast, estrogen suppresses erythropoiesis. This fact might influence potential donor selection in the clinical setting. However, a paucity of donors and the fact that gender is often unknown are usually more significant considerations. Administration of mammalian derived erythropoietin to increase the PCV in birds has proven ineffective (Rosse and Waldmann 1966). In some cases, avian patients with iron storage disease might be used as donors as they tend to have higher than normal PCV and come in regularly for therapeutic phlebotomies (Figure 24.2).

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Figure 24.2 A Toucan donor. Avian patients with iron storage disease can be used as blood donors. They tend to have high PCV and blood is regularly collected for therapeutic phlebotomy.


(Photo courtesy of Erin Harrison, BScHon, DVM, GDipl (Avian Medicine and Pathology).)


The oxygen affinity of avian hemoglobin is less than in mammalian species due to molecular differences; 2,3-diphosphoglycerate is replaced by myoinositol pentophosphate in avian hemoglobin and many avian species contain inositol pentophosphate as well. The lower oxygen affinity of avian hemoglobin shifts the oxygen dissociation curve to the right compared to mammals. This right curve displacement allows healthy birds to more readily extract oxygen (Thrall 2004). Birds also have a two-part respiratory cycle and gas exchange, which is more efficient when compared to mammals and compensates for their increased oxygen demands.


Indications for blood transfusions


Anemia is a common finding in birds presenting for illness and can be a result of numerous acute and chronic disease processes. Documented and speculated causes can be classified as RBC loss (e.g., hemorrhage, coagulopathies, parasitism), increased RBC destruction (e.g., hemoparasites, certain bacterial infections, autoimmune disease), or decreased RBC production (e.g., nutritional deficiencies, chronic infection/inflammation, chronic kidney disease, toxicosis) (Samour 2006; Johnston et al. 2007). A common cause of non-regenerative anemia in birds is anemia of infection or inflammation.


Transfusion triggers


Triggers for blood transfusions in birds are similar to those in mammals. Anecdotally, birds seem to tolerate blood loss better than comparable losses in mammals. Hypovolemic shock secondary to severe acute blood loss occurs after removal of 60% of the total blood volume in ducks (Anas platyrhynchos) (Lichtenberger et al. 2002). Similarly, ducks undergoing a 50% loss of blood volume can be successfully resuscitated using crystalloids combined with colloids alone; a comparison of blood products versus fluid resuscitation has not been investigated (Lichtenberger et al. 2009).


Anecdotally, birds are occasionally presented with chronic disease conditions resulting in anemia with PCVs ranging from 7% to 12%. Some sources recommend a general guideline of transfusion when the PCV decreases below 20% (Samour 2006). However, a transfusion might not be required in a severely anemic bird that is standing, bright, and alert, especially when the anemia develops gradually, as with chronic disease, and when further blood loss is not expected. Decisions regarding when to transfuse should be based on the overall condition of the bird, including factors such as the degree of anemia-related lethargy and other clinical signs such as orthopnea and pale feet (Figure 24.3), and objective parameters such as blood pressure and hemogram abnormalities.

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Figure 24.3 An anemic Gyrfalcon. a. Evidence of orthopnea due to hypoxia from the anemia. b. The foot appears pale due to the anemia.


(Photos courtesy of Erin Harrison, BScHon, DVM, GDipl (Avian Medicine and Pathology).)


If whole blood, blood components, or artificial blood substitutes are unavailable, the importance of tailored fluid therapy cannot be overstated. Particularly with hypovolemic patients, fluid therapy can play a vital role in the restoration of vascular volume, which will ultimately aid in tissue perfusion. Moreover, monitoring the effects of appropriate fluid therapy is done by assessing circulatory function by means of cardiac output. Invasive arterial blood pressure monitoring is ideal for recording changes in circulatory function, but might be impractical and can be substituted (albeit less accurately) with non-invasive blood pressure measurements and careful attention to trends (Muir 2013).


Blood groups and types


To date, the majority of the published work regarding avian blood groups has been performed in chickens, with 28 blood groups described in the species (Hohenhaus 2004), along with the major histocompatibility complex (MHC) B and Y (Gilmour 1962; Briles and Briles 1982; Miller et al. 2004). MHC class IIB gene sequences have also been classified in quail (Shimizu et al. 2004). Early studies of 94 species of passerine birds used antisera to human RBC antigens ABO, Rh, Kell, Duffy, Kidd, and others to test for agglutination. Based on these tests, A, B, AB, and O-“like” reactions were observed, but it was uncertain if they were identical to the same groups in humans (Ferrell 1966). Similar research has been performed attempting to classify the variation in those blood reaction frequencies in song sparrows in the San Francisco Bay area (Ferrell 1966). Further research is needed to classify avian blood groups and determine how they might differ among species and individual birds.


Donor selection


The ideal avian donor is healthy and in good weight, with no history of recent illness. In an emergency situation, it might not be practical to attempt to screen donors for all diseases that might endanger the recipients. For this reason, the ideal donor might be a bird of the same species from the same household. If time allows, collect a single drop of blood from the donor to evaluate PCV, RBC, and white blood cell (WBC) morphology, as well as an estimated WBC count.


Whenever possible, donor birds should be of homologous species (e.g., cockatiel to cockatiel). Select post-transfusion RBC survival time studies indicate that heterologous transfusions result in considerably shorter RBC lifespans. For example, pigeon RBCs administered to raptors result in an estimated survival time of 0.51 ± 0.19 days, while previous studies show that the RBC lifespan after homologous transfusions from pigeons to pigeons is 7.1 days (Sandmeier et al. 1994). Investigations of post-transfusion RBC survival between homologous species (i.e., sun conure to sun conure) and closely related species (i.e., white-eyed conure to sun conure) show similar RBC lifespans of 8.5 and 4.5 days, respectively (Degernes 1999a). These results suggest that while homologous transfusions are ideal, closely related or heterologous transfusions can be considered when a homologous donor is not available.


While homologous (of the same species, e.g. cockatiel to cockatiel) transfusions are considered safest, successful heterologous (between different bird species) transfusions have been performed in multiple avian species. Autologous (transfusion of blood from a donor back to itself), homologous, and heterologous transfusions were studied in cockatiels (Nymphicus hollandicus) and conures of the genus Aratinga (Degernes 1999b). In cockatiels, transfused heterologous RBCs from either Amazon parrots or pigeons had significantly shorter half-lives than both autologous and homologous transfusions. Importantly, the half-lives of the heterologous RBCs decreased significantly with repeated transfusions. However, heterologous transfusions between conures of the genus Aratinga did not result in shorter RBCs half-lives after a single transfusion, therefore in the absence of a homologous donor, a single heterologous transfusion between birds of the same taxonomic genus might be efficacious. Ultimately, many experienced avian practitioners have regularly transfused heterologous species with good to excellent results. While RBC longevity is questionable, the benefits noted might be due to the short-term oxygen-carrying capacity of transfused RBCs and correction of hypovolemia during emergent or critical clinical situations.


Compatibility testing


A high percentage of serologic incompatibility in birds of different species is proposed based on crossmatch testing (Hohenhaus 2004). For example, in birds not previously transfused, crossmatches between the African grey parrot (Psittacus erithacus) and cockatiel (Nymphicus hollandius) were considered incompatible due to hemagluttination (Degernes 1999b). Similarly, the majority of umbrella cockatoo (Cacatua alba) to cockatiel and pigeon (Columbia livia) to cockatiel crossmatches were deemed incompatible due to hemagluttination (Degernes 1999b). Overall, 66% of crossmatches attempted between different avian species resulted in hemolysis or agglutination (Hohenhaus 2004).


The washed-cell incubation technique was used to determine major crossmatch compatibility during experimental evaluation of avian blood transfusions (Degernes 1999a). Gross or microscopic hemolysis or agglutination, scored from 1+ to 5+, was used as compatibility criterion. Birds with low (1+) scores were used for heterologous transfusions. This method requires several steps and might not be practical in urgent clinical settings.


Crossmatching is recommended for transfusions in traditional pet avian species, but crossmatching might not be practical for all avian species and has not been well described in the literature. A simplified partial crossmatch procedure can be performed to decrease potential transfusion-associated complications, namely, immunologic reactions. Two drops of plasma are mixed with one drop of whole blood on a slide at room temperature. Using this modified technique, based on availability of the sample, whole blood from the donor can be matched with plasma from the recipient or vice versa. Agglutination on the slide within 1 minute is suggestive of incompatibility and a different donor should be selected (Lichtenberger 2004).


Blood collection


Avian total blood volume is variable among species, but is approximately 6–8% of total body weight. Therefore, collecting no more than 1% of the body weight (approximately 7–10% of total blood volume) is the accepted collection guideline for donor birds (Shaw et al. 2009). Crystalloid fluid replacement for the donor bird is recommended, minimally equaling the total amount of blood collected.


As blood collection volumes for transfusion are generally larger than those used for diagnostic purposes, manual restraint alone might not be desirable even for experienced avian phlebotomists. Sedation is well described in birds and can be used as an alternative to general anesthesia for many procedures, including venipuncture (Table 24.1). Midazolam alone or in combination with butorphanol has been advocated for sedation in many avian species (Lennox 2011).


Table 24.1 Sedatives and dosages commonly used to facilitate avian phlebotomy



















Drug Dosage Comments
Midazolam 0.25–3.0 mg/kg IM Flumazenil 0.02–0.03 mg/kg IM or 0.05 mg/kg IV to reverse if needed
Diazepam 0.2–1.0 mg/kg IV (preferred) or IM (absorption rate is variable) Same flumazenil dose as midazolam if needed
Butorphanol 0.02–0.04 mg/kg IV
0.4–2.0 mg/kg IM
Reversible with naloxone; low IM dose can be combined with low-dose midazolam

IM, intramuscular; IV, intravascular.


Anticoagulant


Blood is collected into syringes containing an anticoagulant. Sodium citrate, heparin, acid-citrate-dextrose (ACD), citrate-phosphate-dextrose (CPD), and CPD with adenine (CPDA-1) have been described for use in birds (Morrisey et al. 1997). However, blood containing citrate anticoagulants can lower blood ionized calcium concentrations in humans when transfused at high rates, during massive transfusions, or when pre-existing hepatic dysfunction, kidney disease, or other organ failure exists. Citrate anticoagulants might best be reserved for patients with normal calcium levels, but supplementation of calcium and magnesium can alleviate this effect if other anticoagulants are not available or used (Kramer et al. 2003; Davenport and Tolwani 2009; Shaw et al. 2009).


Use of anticoagulants according to the manufacturer’s instructions is recommended to avoid administration of excessive volumes, especially in very small avian patients. Use of heparin (1000 IU/mL) at 0.25 mL per 10 mL of blood collected has also been reported, but heparin is only recommended for immediate transfusion as it is not a preservative (Morrisey et al. 1997). For small volume blood collections (<5.5 mL), companies have custom blood collection systems containing different anticoagulants (S-Monovette syringe tubes, Sarstedt AG & Co, Germany) (Figure 24.4). These systems utilize the blood collection vial as the syringe tube. When the sample is collected, the plunger portion and needle are removable. This technique minimizes contamination and bypasses the need for manually preparing syringes containing anticoagulant.

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Figure 24.4 S-Monovette tubes.


(Sarstedt AG & Co, Germany.)


Lactate measurement


Having a donor that is calm and has not been stressed or undergone vigorous activity is crucial to reduce plasma lactate and cortisol levels, both of which have a negative effect on tissue perfusion and healing (Stevenson et al. 2007). Lactate monitors are available and work similarly to glucometers; they require very small sample volumes, which make them ideal in the exotic critical care setting (Figure 24.5). Lactate concentrations should ideally be as low as possible. Defined reference ranges do not exist in avian species. Normal human, dog, and cat lactate concentrations are generally <2.0 mmol/L (18 mg/dL) (Holahan 2010).

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Figure 24.5 A lactate meter works similarly to a glucometer, using a small volume of blood to measure plasma lactate concentration.


(Image courtesy of Kenichiro Yagi BS, RVT, VTS (ECC, SAIM).)


Component processing and storage


Processing of blood components such as packed red blood cells or plasma is feasible but impractical in most pet bird hospital settings. Larger institutions such as aviaries or zoos can theoretically process larger volumes of blood such as that collected from an ostrich or penguin for heterologous transfusions in emergency situations. Cryopreservation of whole blood or blood components is also impractical in most situations when they might not be utilized before significant degradation of the product occurs.


Leukoreduction


A more recent advancement in transfusion medicine is leukoreduction (LR) (see Chapter 17). Although the practice has not become standard of care in veterinary medicine and is only speculative in avian transfusion medicine, there are many veterinary and human studies that demonstrate benefits of LR (McMichael et al. 2010). Unfortunately, LR in exotic transfusion medicine is still somewhat impractical; there is considerable blood lost during the filtering process, which is not ideal in small species. Likewise, the process of LR can also add time to the procedure, which might not be suitable for emergency situations and there is currently no evidence to support the benefits of LR in avian patients.


Blood administration


Birds requiring blood transfusions are usually in a critical condition. Low-dose sedation often allows safe handling of critically ill birds for placement of a catheter. One of several sedation protocols uses low-dose midazolam (0.25–0.5 mg/kg) and butorphanol (1–2 mg/kg) combined into one syringe and quickly administered intramuscularly (IM) while minimizing handling and stress. Administration of higher dosages of intranasal midazolam with or without IM butorphanol is also efficacious for reduced stress and handling (Mans et al. 2012).


IV catheterization is routinely performed in birds utilizing 24–27 g catheters inserted into the basilic (ulnar), medial metatarsal, or jugular veins (Bowles et al. 2007) (Figures 24.624.8). Catheters are usually secured by suturing them to the skin or by very careful taping.

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Figure 24.6 Location of the jugular vein of a cockatoo.


(Image courtesy of Jill Murray RVT, FLATG, VTS (CP-exotics).)

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Figure 24.7 Arrow points to a basilic (ulnar) vein of a blue-and-yellow macaw.

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Figure 24.8 Location of the medial metatarsal vein of a cockatoo.


(Image courtesy of Jill Murray RVT, FLATG, VTS (CP-exotics).)


When IV catheterization is not possible due to hypovolemia or small patient size, intraosseous (IO) catheterization is a viable option. After sedation, a local block (topical or subcutaneous) can help to reduce struggling during placement. The proximal tibiotarsus or distal ulna are the recommended IO sites (Figure 24.9). The humerus and femur are pneumatic bones and should not be used for IO catheterization.

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Figure 24.9 Intraosseous catheter placement in the distal ulna of a crow.


The initial transfusion rate should be approximately 2.5–5 mL/kg/hour for the first 15–30 minutes. If no transfusion-associated complications are observed during this initial monitoring period, the rate can be increased up to a maximum of 20 mL/kg/hour. The blood is administered continuously using a pediatric or syringe pump with a filter (Figure 24.10) or could be injected directly with a syringe for small volume transfusions (Figure 24.11

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Sep 27, 2017 | Posted by in GENERAL | Comments Off on Avian Transfusion Medicine

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