Alternative Transfusion Methods

Chapter 21
Alternative Transfusion Methods

Sophie Adamantos and Caroline Smith

Small Animal Hospital, Langford Veterinary Services, University of Bristol, Langford, North Somerset, UK

Introduction

Alternative transfusion methods include techniques such as autotransfusion of shed blood either with or without cell salvaging methods, as well as xenotransfusion. Autotransfusion, in this context, describes the use of salvage and re-administration of shed blood during hemorrhage. These techniques are not commonly performed in small animal practice, but knowledge of suitable processes and specific indications can be lifesaving in some circumstances. Due to the relative infrequency with which these techniques are performed, there is limited peer-reviewed evidence in the veterinary literature on which to base recommendations.

Veterinary transfusion medicine has progressed significantly during the last 20 years, allowing storage and provision of blood products through blood banks. There has been a significant improvement in the ability to treat anemia because of this. Despite these advances in blood banking, blood products remain limited in supply. In large-breed dogs there can be issues with the provision of enough blood to ensure adequate red cell mass. The use of autotransfusion techniques can provide a safe source of large volumes of autologous blood, reducing the risk of transfusion reactions compared with allogenic red cell transfusion.

This chapter will describe the use of xenotransfusion, when blood is transfused between different species (e.g., dog blood administered to cats), as well as autotransfusion, whereby autologous shed blood is administered back to the patient in an emergent situation either directly or using cell-separator devices.

Xenotransfusion

Xenotransfusion describes transfusion of blood between different species and is most commonly reported in modern veterinary medicine between dogs and cats. Historically, blood has been administered between many species, particularly from cattle, sheep, and dogs to people (Roux et al. 2007). Although there are reports of success associated with xenotransfusion to people, there is a high incidence of acute hemolytic reactions and the practice has been abandoned (Roux et al. 2007). Additionally, human blood banking has all but removed the need for other sources of blood.

Within veterinary species, cats seem the most appropriate species to benefit from xenotransfusion. This is due to the difficulty in obtaining feline blood with regards to the amount potentially required and blood type incompatibilities. Dog-to-cat blood transfusions have been reported a number of times in the literature and also in the worldwide press (Hessler et al. 1962; Gowan 2004; Shears 2013; Weingram 2014). Although there is limited published evidence on the efficacy of xenotransfusions in cats, the practice is routine in some parts of the world (Bovens and Gruffydd-Jones 2013).

Experimental work performed in the 1960s investigated the effects of transfusing canine blood to cats (Hessler et al. 1962; Clark and Kiesel 1963; Rene 1968; Lautie et al. 1969). There were a number of findings that should impact the decision about whether xenotransfusion is useful or recommended between these species. No major crossmatch incompatibilities were identified between the recipient cats and donor dogs prior to transfusion, but minor crossmatch incompatibilities were occasionally recognized during transfusion (Hessler et al. 1962; Rene 1968; Lautie et al. 1969). By 7 days after the transfusion, the cats in the study had developed antibodies to canine blood, precluding repeat xenotransfusion (Hessler et al. 1962; Rene 1968; Lautie et al. 1969). In cases where repeat xenotransfusion was attempted beyond 7 days from the first, severe and often life-threatening transfusion reactions were observed (Hessler et al. 1962; Lautie et al. 1969). The average life span of xenotransfused cells is short compared to allogenic transfusion (3.6 days vs 30 days) (Clarke and Kiesel 1963; Marion and Smith 1983). The major advantages and disadvantages of xenotransfusion are summarized in Table 21.1.

Table 21.1 Advantages and disadvantages of xenotransfusion

Advantages	Disadvantages
Easily available blood source	Risk of acute hemolytic transfusion reactions
	Risk of delayed hemolytic reactions
	Short life of transfused cells
	Unsuitable for administration more than once

Because of the many disadvantages, xenotransfusion is only clinically useful in emergent situations when there are no alternatives and should be limited to a single event only. Xenotransfusions should not be considered appropriate in situations where allogenic blood products are available and should never be substituted for appropriate species-matched transfusions. The little data currently available refers to canine donor to feline recipient xenotransfusion. Little or no data exists relating to transfusions between other species. If attempted, this would be considered experimental and cannot be recommended.

If a dog-to-cat xenotransfusion is considered the only option, doses and rates should be similar to those used during allogenic transfusions and blood should be collected and anticoagulated routinely. Major and minor incompatibility testing is recommended prior to considering xenotransfusion and the owner should be appropriately informed of the significant risk associated with the procedure. As minor incompatibility reactions have occasionally been reported pre-transfusion, the use of packed red blood cells is preferable to whole blood, as this will reduce the risk of reactions associated with xenogenic antibodies in the plasma (Bovens and Gryffydd-Jones 2013). With the introduction and availability of alternative oxygen-carrying solutions (see Chapter 6), the use of xenotransfusions should be limited to those situations when there is no alternative.

Autologous transfusion

Autotransfusion is the administration of autologous blood, in other words blood taken from a patient is re-transfused into the same patient. There are two main situations when autologous transfusion is used. The first is when blood is collected from a patient in anticipation of hemorrhage during surgery, for re-infusion after bleeding is controlled (e.g., pre-operative donation, acute normovolemic hemodilution). The second is when significant active hemorrhage occurs perioperatively and the blood is salvaged for re-infusion. Pre-operative donation and acute-normovolemic hemodilution are rarely used in veterinary medicine and are discussed elsewhere (see Chapter 20). This chapter will limit discussion to the salvage and re-administration of blood shed during hemorrhage.

Theoretical benefits of autologous transfusion

The advantages and disadvantages of autologous blood administration are summarized in Table 21.2. Briefly, because autologous blood does not contain foreign antigens, the major risks of transfusion such as acute hemolytic and anaphylactic reactions are avoided and, as such, the need for blood typing or crossmatching is removed.

Table 21.2 Advantages and disadvantages of autologous blood transfusion

Advantages	Disadvantages
Decreased risk of transfusion reactions	Potential for bacterial contamination
Decreased risk of infectious disease transmission	Damage to red blood cells, causing hemolysis
Reduced risk of transfusion-related immunosuppression	Dilutional coagulopathy
Decreased time to administration	Cost (cell salvage devices)
No risk of immunization from foreign antigens
Cost (direct re-infusion)

The administration of allogenic blood in people has been associated with a number of adverse events, including transfusion reactions, immunomodulation, increased mortality and length of hospital stay, transmission of infection, and transfusion related acute lung injury (TRALI) (Crescenzi et al. 2012). Meta-analysis of the human literature has also demonstrated that greater duration of storage of red blood cell (RBC) products is positively correlated with increased risk of death in recipient patients (Wang et al. 2012) and there is a suggestion that this might also occur in dogs (Hann et al. 2014). A recent study identified increased procoagulant and proinflammatory microparticle formation in RBC products stored beyond 7 days (Herring et al. 2013). The use of autotransfusion avoids storage and therefore minimizes the risk of storage lesions.

Morbidity and mortality associated with transfusion in veterinary species are sparsely described compared to human medicine. Non-hemolytic febrile reactions, acute hemolytic reactions, allergic and anaphylactic reactions, and delayed hypersensitivity reactions are recognized and well documented (Klaser et al. 2005; Sukullaya and Anuchai 2006; Tocci 2010). Volume overload, acute kidney injury, pneumonia and other infections, as well as acute lung injury are also described in dogs, but the relationship between cause and effect is yet to be clearly established (Holowaychuk et al. 2014; Thomovsky and Bach 2014). There is increasing suspicion that occult transfusion reactions might be overlooked in transfusion recipients with ongoing underlying disease.

In dogs, a post-transfusion inflammatory response documented by significant increases in neutrophils, C-reactive protein, and fibrinogen was attenuated by use of a pre-storage leukocyte reduction filter to remove unwanted leukocytes, microparticles, and other nucleated cells. This suggests that unfiltered products might stimulate a significant and possibly detrimental inflammatory response, although the clinical significance of this is currently unknown (McMichael et al. 2010). Administration of autologous blood is thought to be less likely to cause adverse events due to the reduced storage time and avoidance of allogenic antigen exposure and is therefore considered safer.

In dogs, life-threatening transfusion reactions are relatively uncommon, and therefore the benefit of administration of autologous versus allogenic blood is unknown. In cats, the administration of correctly typed blood products is associated with a low risk of transfusion reaction (Castellanos et al. 2004; Klaser et al. 2005; Roux et al. 2008). Blood type incompatible products can be associated with life-threatening transfusion reactions, making autologous transfusion potentially more desirable. However, autotransfusion can be more challenging in smaller patients, including cats.

Methods of autologous transfusion

There are two methods by which shed blood can be re-administered to a patient: (1) direct re-infusion of collected blood or (2) cell salvage, a process of concentrating the cells and removing waste products with the use of a device. Whichever method is used, it is important to be aware that it is not usually possible to salvage all shed blood. Depending on the site of hemorrhage, as little as half of the shed blood might be salvaged. Blood collected using cell salvage methods typically has a lower packed cell volume (PCV) than circulating blood because the salvaged blood is diluted by irrigation fluid and some cells are lost through mechanical hemolysis.

Methods for direct re-infusion

There are few clinical and experimental reports of direct infusion of shed blood back to dogs (Zenoble and Stone 1978; Crowe 1980, 2004; Purvis 1995; Higgs et al. 2015) and only two reports in horses (Waguespack et al. 2001; Finding et al. 2011). Reports in cats and other veterinary species are lacking. While there is little published on the clinical use of this technique, it has been used extensively in veterinary medicine and has proven lifesaving in many situations (Buckley et al. 2009; Higgs et al. 2015).

In a recently published report, 25 dogs received a median volume of 29.3 (range 2.9–406.9) mL/kg of blood salvaged from the abdominal (76%), thoracic (20%), or both (4%) cavities. Underlying causes of hemorrhage included trauma (56%), ruptured or bleeding neoplasia (32%), and coagulopathy secondary to brodifacoum toxicity (12%). Complications included hypocalcemia (24%), hemolysis (26%), and coagulopathy (80%), which might have been secondary to anticoagulant use or the underlying disease process. More than two-thirds (68%) of the dogs survived to discharge and the dogs that died were either euthanized or experienced cardiopulmonary arrest secondary to uncontrollable hemorrhage (Higgs et al. 2015). Anecdotally, direct autotransfusion is thought to improve outcome, especially when allogenic blood products are not available.

Direct infusion implies the sterile collection of blood from the body cavity of the animal and re-infusion into the same animal. Although blood shed into a body cavity is usually defibrinated within 45 minutes, the use of anticoagulant is recommended in case of active hemorrhage. A retrospective study documented anticoagulant use during 52% of autotransfusion procedures in dogs (Higgs et al. 2015). Anticoagulants containing citrate (e.g., sodium citrate or anticoagulant citrate dextrose solution A (ACDA)) are preferred in these situations, as regular (unfractionated) heparin has a risk of systemic heparinization upon re-infusion (Oller et al. 1976). The amount of citrate used is not clearly defined, but the authors use doses similar to those used for routine blood donation (i.e., 1 mL ACD solution to 7–9 mL of blood collected). Lower doses have also been reported (e.g., 37.5 mL of 2% sodium citrate solution or ACD to 500 mL blood) (Crowe 1980). When employing these techniques, underestimation of the volume of blood collected can result in over-anticoagulation. This can cause coagulopathy or hypocalcemia upon re-infusion of the collected blood, depending on the anticoagulant used, so close monitoring is recommended during re-administration should the volume of blood collected be less than expected.

Blood from body cavities can be aspirated directly into syringes (Figure 21.1), collected by centesis into a blood collection bag, or collected under gentle suction into a sterile container using a Poole tip catheter (Crowe 1980). The supplies needed and techniques used are described in Boxes 21.1–21.3 and are illustrated in Figures 21.2 –21.5. Regardless of the technique used, the blood must be collected into a sterile device containing anticoagulant solution (e.g., blood collection bag or pre-filled syringe) or immediately transferred from the sterile collection device into a sterile blood collection bag (Figure 21.6) or syringe containing anticoagulant (Figure 21.7), so that it can be administered to the animal or stored until use. The blood must be administered through a blood administration set containing a 170–210-micron filter or 18-micron filter (Hemonate, Utah Medical Products, Midvale, UT), with routine patient monitoring as per any other allogenic transfusion. A retrospective study of dogs undergoing autotransfusion documented that blood was re-infused through a 210-micron filter in the majority of patients (78%) and an 18-micron filter in the remaining (22%) dogs (Higgs et al. 2015). It is important to avoid collection of air with the blood as inconsistent suction pressure and frothing can cause cellular damage and hemolysis.