Chapter 2
Component Therapy
Julie M. Walker
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin, USA
Introduction
Blood collected from a donor can be utilized in many ways. Although a unit of whole blood (WB) can be transfused or stored after collection without further processing, separation of the unit into blood components can provide several benefits. This chapter provides an explanation of component therapy as it compares to the transfusion of WB, highlighting the advantages and disadvantages of these practices. A general overview of the most commonly administered blood components will also be provided.
Whole blood
Description and contents
Veterinary hospitals and blood banks that practice traditional blood banking begin by collecting a standardized volume of blood from a donor, which is immediately mixed with an anticoagulant-preservative solution as it flows into the primary collection container. At the time of collection, WB contains all components of circulating blood including red blood cells (RBCs) and white blood cells (WBCs), platelets, coagulation factors, albumin, globulins, electrolytes, etc., at concentrations that were present in the donor. This product, known as fresh whole blood (FWB), can be transfused immediately or stored briefly (<8 hours) at room temperature prior to transfusion. WB can also be stored at 4 °C (stored whole blood, SWB) for up to 35 days depending on the anticoagulant-preservative solution used, or can be processed into blood components (Bucheler and Cotter 1994; Callan 2010).
Platelets in FWB maintain the ability to aggregate for at least 8 hours when stored at room temperature (Tsuchiya et al. 2003). However, platelet aggregation and factor V and VIII concentrations in SWB decrease in a time-dependent manner during storage at 4 °C (Nilsson et al. 1983; Nolte and Mischke 1995; Solheim et al. 2003; Jobes et al. 2011; Pidcoke et al. 2013).
Indications
The transfusion of FWB is indicated for the treatment of anemia that occurs concurrently with coagulopathy, thrombopathia, or severe thrombocytopenia. Patients with severe traumatic injury and marked hemorrhage who require massive transfusion might also benefit from a FWB transfusion (Kauvar et al. 2006; Repine et al. 2006; Spinella 2008; Spinella et al. 2009; Cotton et al. 2013). Similarly, SWB is indicated for the treatment of anemia with coagulopathy, but this product would not be appropriate to correct thrombocytopenia, thrombopathia, or deficiency of factors V or VIII. WB, while not ideal, can also be administered to patients with euvolemic non-coagulopathic anemia, particularly when component therapy is not readily accessible.
Advantages
The most notable advantages of collecting and transfusing WB are availability and practicality for private practices that infrequently administer blood transfusions. With proper understanding of transfusion principles, identification of a healthy blood donor and proficiency in venipuncture and aseptic technique, FWB collection and transfusion can be safely performed in most veterinary settings. If SWB will be kept for later use, the hospital must use a refrigerator that can consistently maintain a constant temperature between 1 and 6 °C. Conversely, FWB can be collected in a more flexible manner when used immediately; the phlebotomist can even draw the desired amount of blood into syringes that have been pre-filled with anticoagulant-preservative solution. This practice allows the collection of only the desired volume of blood, but is inappropriate for long-term storage as this method utilizes an open collection system, which limits storage time to less than 24 hours (Roback et al. 2011).
Disadvantages
Being able to perform blood donation at the time of patient need makes it necessary to complete comprehensive health and infectious disease screening on donors well in advance of donation. It can be challenging to find blood donors that are available at all times for blood donation on an “on call” basis. When a patient has an urgent need for a blood transfusion, the delay in treatment that occurs while contacting the blood donor’s owner, awaiting donor arrival, and collecting the FWB unit can also be a significant disadvantage. Additionally, the administration of FWB or SWB to anemic patients without hypovolemia or coagulopathy predisposes recipients to volume overload and antigenic stimulation secondary to unnecessary plasma administration. Because of this, banking and administration of component therapy has several advantages over FWB and SWB.
Component therapy
Background concepts
The separation of WB into its constituents for further storage prior to administration is known as component therapy. FWB can be processed into a variety of different components that can be transfused based on individual patient need (Table 2.1). Most established in-hospital and commercial blood banks are able to create these WB-derived components. While most veterinary blood banks process components by centrifugation of collected blood, specific blood components can also be collected directly from a donor using apheresis, an extracorporeal process that employs differential centrifugation within a tubing system to selectively collect one or more blood components (e.g., platelets or plasma), while immediately returning the unused portion to the donor. There has been an increase in the use of apheresis for the collection of RBC, platelet, and plasma units from human blood donors in the United States from 2008 to 2011 (Department of Health and Human Services 2013). The production of apheresis-derived components requires access to and experience with specialized equipment, therefore these techniques are performed in only a small number of commercial animal blood banks and veterinary teaching hospitals.
Table 2.1 Overview of blood products, including contents, indications, and storage conditions
Contentsa | Main indications | Storage conditions | |
Fresh whole blood | RBC, WBC, platelets, all coagulation factors, albumin, globulin | Anemia with coagulopathy/platelet disorder, severe hemorrhage requiring massive transfusion | Room temperature for up to 8 hours |
Stored whole blood | RBC, WBC, non-viable platelets, coagulation factors excluding labile factors, albumin, globulin | Blood loss anemia | Refrigerated at 1–6 °C for up to 28 daysb |
Packed red blood cells | RBC, WBC, non-viable platelets, small amount of plasma | Symptomatic anemia of any etiology | Refrigerated at 1–6 °C for up to 42 daysb |
Platelet-rich plasma | Platelets, all coagulation factors, albumin, globulin | Marked thrombocytopenia with critical hemorrhage | Room temperature storage under constant gentle agitation for up to 5 days |
Platelet concentrate | Platelets, low volume of fresh plasma | ||
DMSO-preserved frozen canine platelet concentrate | Platelets, small volume of plasma, 6% dimethyl sulfoxide | Frozen at ≤ –18 °C for up to 6 months | |
Lyophilized canine platelets | Platelets | Refrigerated at 1–6 °C for up to 24 months | |
Fresh frozen plasma | All coagulation factors, albumin, globulin | Coagulopathy with clinical evidence of hemorrhage, coagulopathy without hemorrhage but with planned invasive procedure, coagulopathy without hemorrhage or planned invasive procedurec | Frozen at ≤ –18 °C for up to 12 months |
Frozen plasma | All coagulation factors (lower concentrations of factors V, VIII, vWF) | Anticoagulant rodenticide intoxication; coagulopathy due to factors II, VII, IX, X, XI or fibrinogen deficiency | Frozen at ≤ –18 °C for up to 5 years |
Refrigerated plasma | All coagulation factors with mildly reduced concentrations of some factors | Emergent treatment of life-threatening coagulopathy | Refrigerated at 1–6 °C for up to 14 days |
Cryoprecipitate | Concentrated factors VIII, XIII, vWF, fibrinogen, and fibronectin | Hemophilia A, von Willebrand disease, fibrinogen deficiency | Frozen at ≤ –18 °C for up to 12 months |
Lyophilized cryoprecipitate | Concentrated factors VIII, XIII, vWF, fibrinogen, and fibronectin | Hemophilia A, von Willebrand disease, fibrinogen deficiency | Refrigerated at 1–6 °C for up to 18 months |
Cryosupernatant | Factors II, V, VII, IX, X, and XI | Deficiency of factors II, V, VII, IX, X, or XI such as anticoagulant rodenticide intoxication | Frozen at ≤ –18 °C for up to 12 months |
RBC, red blood cells; WBC, white blood cells; vWF, von Willebrand Factor.
a Minimal leukocyte content if leukoreduction techniques are applied.
b Shelf life depends on the anticoagulant-preservative solution used.
c Controversial.
Lyophilization, simply the process of “freeze drying”, has also been used to preserve and extend the shelf-life of blood products. During the process of lyophilization, the prepared blood product is injected into a vial and loaded onto a lyophilizer, where it undergoes rapid freezing. After the product is frozen, it is heated under very low (subatmospheric) pressure conditions, causing sublimation of the solvent from its frozen (solid) phase directly to its gas phase. The water vapor is removed by the machine, leaving behind a dry product that can later be reconstituted for use (Fetterolf 2010). At this time, lyophilized canine albumin and cryoprecipitate products have been produced by a commercial blood bank (Animal Blood Resources International, Stockbridge, MI) for clinical use and lyophilized canine platelets have been used in a research setting (Davidow et al. 2012).
Instrumentation for blood component production
Over the past 30 years, there has been a significant increase in the transfusion of blood components in comparison to WB (Stone et al. 1992; Callan et al. 1996). This change is supported by a growing number of veterinary blood banks, which have increased the availability of these products. In order to produce blood components on site, a practice must have access to specialized equipment. Most importantly, the preparation of blood products requires access to a large-capacity temperature-controlled centrifuge (Figure 2.1). This type of centrifuge has swinging buckets that each hold a unit of WB with integrated satellite bags. The precise technique for centrifuge speed, time, and temperature is specific to the type of product produced.
After a unit of WB is centrifuged, it is carefully removed from the centrifuge and hung on the hooks of a plasma extractor (Figure 2.2A). The fluid path to a satellite bag is opened and the front panel of the plasma extractor is slowly pressed against the bag to remove the desired volume of plasma from the primary collection bag (Figure 2.2B). The connecting fluid path is closed with atraumatic line clamps (Figure 2.3) and then the lines are sealed using aluminum sealing clips or a heat sealer (Figure 2.4). Other equipment necessary for blood component production would include a line stripper (Figure 2.5), which is used to apply aluminum sealing ring clips and to move blood from the collection line into the primary collection bag, as well as a gram scale used to measure the weight of blood component in each bag. Additionally, a balance can be useful to ensure that weights of centrifuge buckets are equal (Figure 2.6). It is impractical for many veterinary practices to own all of these instruments, particularly a blood-bank centrifuge, as they can be quite costly and take up a large amount of space. Instead, many veterinarians purchase blood components from larger scale veterinary blood banks such as those listed in Table 2.2.
Table 2.2 Veterinary blood banks located in the United States, Canada, the United Kingdom, and Australia that distribute blood products to regional veterinarians
Blood bank name | Location | Website |
Animal Blood Resources International | Stockbridge, Michigan, United States Dixon, California, United States | www.abrint.net |
Best Friends Blood Bank | Decatur, Georgia, United States | www.bestfriendsbloodbank.com |
Blue Ridge Veterinary Blood Bank | Purcellville, Virginia, United States | www.brvbb.com |
Hemopet | Garden Grove, California, United States | www.hemopet.org |
Hemosolutions | Colorado Springs, Colorado, United States | www.hemosolutions.com |
Nine Lives Blood Services | Lansing, Michigan, United States | www.catbloodbank.com |
Northwest Veterinary Blood Bank | Bellingham, Washington, United States | www.northwestbloodbank.com |
The Ohio State University | Columbus, Ohio, United States | www.vet.osu.edu/vmc/companion/our-services/animal-blood-bank |
The Pet Blood Bank | Lago Vista, Texas, United States | www.petshelpingpets.com |
Rocky Mountain Blood Services: | Parker, Colorado, United States | www.rockymountainbloodservices.com |
Sun States Blood Bank for Animals | Sahuarita, Arizona, United States | www.sunstates.org |
The Veterinarians’ Blood Bank | Vallonia, Indiana, United States | www.vetbloodbank.com |
Canadian Animal Blood Bank | Winnipeg, Manitoba, Canada Edmonton, Alberta, Canada | canadiananimalbloodbank.ca |
LifeStream Animal Blood Bank | Kingston, Ontario, Canada | www.animalbloodbank.ca |
Pet Blood Bank (PBBuk) | Leicestershire, United Kingdom | www.petbloodbankuk.org |
University of Melbourne | Werribee, Victoria, Australia | vh.unimelb.edu.au/bloodbank |
Equipment for blood component storage
If blood products are to be stored for future use, the hospital must own an appropriate refrigerator and freezer. It is critical that the refrigerator reliably maintains a temperature of 1–6 °C (Roback et al. 2011) at all times and is dedicated to the purpose of storing blood products (Figure 2.7A). Careful monitoring and control of refrigerator temperature is critical, as warmer temperatures might predispose blood products to bacterial growth, and colder temperatures might lead to freezing of RBCs, causing hemolysis and recipient morbidity or mortality (Patterson et al. 2011) (Figure 2.7B). Some newer blood bank refrigerators are equipped with complex monitoring systems that record temperature measurements over time, sound an alarm when storage conditions are not consistent with set ranges, and allow password protection for access.
Frozen blood products must be kept at temperatures at or below –18 °C. Freezers with automatic defrost functions should not be used for the storage of blood products, as repeated freeze–thaw cycling of blood products could occur. As the packaging of frozen blood products can be brittle when frozen, handling of these products should be gentle and kept to a minimum. The blood-bank inventory should be monitored and recorded regularly and blood products should be discarded at the time of expiration.
The rise of component therapy
Over the past 30 years there has been a progressive trend toward the use of component therapy for the treatment of anemia in veterinary patients, but this transition has occurred much more quickly in dogs than cats. In the 1980s, red cell transfusions were most frequently provided to dogs in the form of WB (FWB or SWB) (Stone et al. 1992; Howard et al. 1992). Between 1986 and 1989, two publications cite an increase in the number of packed red blood cell (PRBC) transfusions in dogs (Stone et al. 1992; Kerl and Hohenhaus 1993). While this transition towards PRBC transfusion continued in dogs (Callan et al. 1996), most data published from the 1990s demonstrated the persistence of WB as the most frequent red cell product transfused in cats (Weingart et al. 2004). The transfusion of PRBCs in cats became more frequent around the year 2000, with the incidence of PRBC transfusion in cats receiving red cell transfusions ranging from 15% (Klaser et al. 2005) to 47% (Castellanos et al. 2004). In comparison, recent reports of transfused dogs show that 94–96% of red cell transfusions are provided as PRBCs (Lux et al. 2013; Thomovsky and Bach 2014). Although the proportion of PRBC transfusions has increased over time, recent feline studies still demonstrate a relatively frequent use of WB (43% of red cell transfusions) for anemic cats (Roux et al. 2008).
One likely reason for the increased transfusion of blood components is the emergence of several commercial veterinary blood banks that distribute blood products to veterinarians in private practice. As of 1992, there were only two commercial veterinary blood banks that were known to distribute canine and feline blood products (Stone et al. 1992). Without access to large-format centrifuges and other blood-banking equipment, it was most common for veterinarians in practice to have access to WB that was collected at their own practice (Howard et al. 1992). Today there are at least 16 blood banks that distribute blood products to practicing veterinarians around the world (Table 2.2). As discussed throughout this chapter, WB might be more convenient for some practices to collect or obtain, but blood components allow for transfusions to be more targeted towards patient need.
Advantages
The practice of component therapy is advantageous not only to the individual patient, but also to the overall companion animal population. From a population perspective, blood component production allows greater conservation of precious biological products. The production of blood components (e.g., PRBCs and fresh frozen plasma [FFP]) allows two or more patients to benefit from a single blood donation. The production of plasma and plasma-derived products from WB also prolongs storage times, extending the shelf-life of the plasma component by up to several years. Administration of blood components also enhances the safety of transfusion for individual patients. Clinicians are able to treat the primary hematologic abnormality, such as anemia or coagulopathy, without transfusion of portions of WB that are not expected to provide benefit to the recipient. The administration of unnecessary blood components puts patients at an increased risk of volume overload and exposure to antigens that could initiate a transfusion reaction.
Disadvantages
The disadvantages of component therapy relate to the logistics of product production, storage, and purchase. As discussed earlier, many veterinary practices are unable to produce blood components due to a lack of access to an appropriate centrifuge and other necessary equipment. For this reason, many veterinary professionals purchase blood components from commercial veterinary blood banks. However, if such blood banks are geographically distant from the veterinary clinic, it might be difficult to obtain products at the time of need. Because it can be challenging for a clinic to estimate the need for blood products in advance, reliance on distant blood banks for blood products can lead to understocking in times of need or overstocking when demand for blood products is low.
Handling and storage of blood components can affect product quality. During the production of WB-derived components, each step in processing could lead to degradation of cellular or protein concentration or quality. For example, approximately 26% of platelets are lost during the production of platelet concentrate from one unit of canine FWB (Abrams-Ogg et al