VETM 5291: Transfusion Medicine PDF

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This document covers transfusion medicine, focusing on blood donors and recipients, including different blood types for various animals (dogs, cats, and horses). It also outlines potential transfusion reactions and considerations for various species of animals. This document is part of Veterinary Education.

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VETM 5291: Transfusion Medicine Major Learning Goals: 1) List the characteristics of a good blood donor and calculate the maximum donation volume 2) List the red blood cell “transfusion triggers” 3) Be able to list the important blood groups in dogs, cats and horses and...

VETM 5291: Transfusion Medicine Major Learning Goals: 1) List the characteristics of a good blood donor and calculate the maximum donation volume 2) List the red blood cell “transfusion triggers” 3) Be able to list the important blood groups in dogs, cats and horses and how the blood groups affect transfusion decisions 4) Be able to interpret blood typing tests for dogs and cats 5) Know indications for cross matching blood, the difference between major and minor cross match, and how to interpret cross match results 6) Know the different types of transfusion reactions and strategies for avoiding and monitoring for such reactions. Blood products have become increasingly available and an integral part of clinical practice. Blood products are used to treat anemia, coagulopathy, and hypoproteinemia. In order to successfully use blood products, it is important to know indications for blood product administration, the types of products available and their indications for use, characteristics of successful blood donors, and methods used to ensure compatibility between the patient and donor. the products that are available, their indications for use, and how to administer the products safely. There are many blood products available (see table at end of document), but the most commonly utilized are fresh whole blood, packed red blood cells (pRBCs), and plasma. RBC-containing products are indicated to treat animals with decreased DO2 secondary to significant anemia. Animals only needing increased oxygen carrying capacity can be administered pRBCs. While animals needing both RBCs and either proteins or coagulation factors can be given fresh whole blood (or stored whole blood). Animals needing only proteins can be given plasma (or albumin, if available) and those needing coagulation factors are given plasma or one of its derivatives (see table). The species of animal may also determine what products are available to clinicians. Blood banking is most well developed for dogs and cats where a wide array of products can be purchased. Many practices also have a identified local donors to obtain fresh whole blood, especially if need for product is infrequent in that practice. Blood products for large animals and exotic species are usually obtained fresh from a local donor, rather than being purchased or stored and ready for use. As such, fresh whole blood is widely used, although pRBCs and plasma can be produced if equipment is available. Donor characteristics Blood donors are ideally young, fit, otherwise healthy animals that have never received a blood transfusion and are generally tolerant of handling. It is ideal to identify potential donors and prescreen them for health (CBC, chemistry), blood type, and for potential blood-borne or vector-transmitted pathogens that could be transferred to the recipient via transfusion. Dog donors are optimally DEA 1 negative (“universal donor”) while both A and B feline donors are required since cats must receive type specific VETM 5291: Transfusion Medicine transfusion. Universal pathogen testing includes Anaplasma, Babesia, Bartonella, Ehrlichia, Leishmania, and Mycoplasma in dogs and Anaplasma, Bartonella, Mycoplasma, FeLV, and FIV in cats. Additional pathogen testing is dependent on regional pathogens where the donor lives or has travelled. Updated ACVIM guidelines for donor screening can be found here: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.13823 In large animals, especially horses, the donors are preferred to be male since females can be sensitized to fetal antigens. Donor horses should be Qa and Aa antigen and antibody negative. Horses used to provide plasma for treating failure of passive transfer for donkeys or mules should be certified “donkey factor free”. Donkeys and mules should not be used as donors for horses. Horses should be screened for Equine infectious anemia, equine viral arteritis, and other regional pathogens. Relatively little is known or considered when choosing donors for small mammals, birds, and reptiles. When possible, a young, otherwise healthy animal of the same species is preferred. The ideal blood donation is no more than 10% of the donor’s blood volume. A donation of 20% blood volume can be handled by a healthy donor and is considered the maximum donation volume. Fluid therapy (IV bolus) is sometimes administered when a large donation is taken to address the hypovolemia. (A healthy donor should not approach hypovolemic shock until closer to 30% blood volume has been lost.) RECIPIENT CHARACTERISTICS Red Cell Transfusion trigger Utilization of RBC products is generally dependent on the patient demonstrating “transfusion triggers”. Studies in animals have demonstrated that oxygen delivery to the tissues is maximized at hematocrits of between 30-40%. In otherwise healthy normovolemic patients, current guidelines support the safety of hematocrit levels as low as 18%. Other factors to consider when deciding on the need for blood transfusion should include clinical signs of anemia, the rate of ongoing losses, the chronicity of the anemia, and the presence of concurrent diseases that may impair the patient’s ability to compensate for the anemia (heart failure, for example) or increase a patient’s oxygen extraction rate (eg, sepsis). Signs of anemia, including tachycardia, tachypnea, increased lactate, weakness, collapse, hypotension, decreased mental status, etc, occur at very low PCVs and should prompt immediate attention. Patients with acute anemias, as from IMHA or hemorrhagic shock (occurs with acute blood loss of >~30%), often require transfusions at higher PCVs than patients with chronic anemias, such as occurs with chronic renal failure or bone marrow disease. Patients with chronic anemia may be more tolerant of their anemia because of a rightward shift in the oxy-hemoglobin dissociation curve (increased oxygen offloading in peripheral tissues), and may consequently not demonstrate need for a transfusion despite very low hematocrits. VETM 5291: Transfusion Medicine Strong triggers for plasma transfusion include both coagulopathy associated with disorders of secondary hemostasis and failure of passive transfer. Plasma is also used to treat clinical hypoproteinemia ASSESSING COMPATIBILITY BETWEEN DONOR AND RECIPIENT Just like all cells in the body, red blood cells are covered with proteins and complex carbohydrates that can be antigenic. Some of the antigens on RBCs are consistent within a species. That is, the antigens distinguish a canine RBC from feline from human, etc. There are other antigens that are present on RBCs of some, but not all members of the species; it is this group of antigens that make up the different blood types within a species. Blood Typing Canine blood types: Most antigens on canine RBCs are referred to as Dog Erythrocyte Antigens (DEA). The DEA 1 antigen (previousy DEA 1.1 and 1.2) is the most important canine blood type. Approximately 50-60% of dogs are DEA 1 positive, that is they possess the DEA 1 antigen on their red cells. The DEA 1 antigen is the only DEA routinely tested for in clinical practice because of all the antigens, DEA 1 evokes the strongest immune response in dogs DEA 1 negative dogs receiving DEA 1 positive blood. Dogs can also be positive or negative at each of the other loci: DEA 3, 4, 5, 6, 7 and 8. Additional RBC antigens include Kai1, Kai 2, and the Dal antigen, which is common on canine RBCs but missing from some dogs, leading to development of strong alloantibodies in those receiving blood transfusions. Ideally, all dogs should be blood typed prior to transfusion; although, a naïve DEA 1 negative recipient (has not been transfused previously) will likely tolerate receiving DEA 1 positive blood one time. There are no in-hospital tests for the Dal antigen. A true “universal donor” should be negative at all loci; but in practice, DEA 1 negative is often considered the “universal donor” for dogs. Dogs are not born with preformed antibodies against the other blood types (alloantibodies). Dogs that are DEA 1 negative that receive blood from a DEA 1 positive donor will ultimately make strong antibodies against the DEA 1 antigen. Feline blood types: Cats can either be Type A, B or AB. As a whole, approximately 98% cats in the United States are type A. Type B accounts for 0.3% (in the northeast US) to 4.7% (on the western coast of the US) of the feline population. Type B is more common in certain breeds of cats including British Shorthair and Devon Rex (40-50%) and Cornish rex and exotic shorthair (20- 30%). Ten to 20% of Abyssinian, Japanese bobtail, Persian, Himalayan Somali, and Sphinx breeds may also be Type B. Less than 5% of Maine coon and Norwegian forest cats are type B and there were no Type B American shorthair, Burmese, ocicats, or oriental shorthairs. Type AB is very rare. Unlike dogs, within their first few weeks of life, cats can develop alloantibodies against the other blood type. Approximately 30% of type A cats have weak preformed anti-B antibodies. All type B cats are born with strong anti-A antibodies. Type A cats receiving type B blood may have a transfusion reaction. The reactions are usually not life-threatening but may shorten the RBC VETM 5291: Transfusion Medicine lifespan. Type B cats receiving even a few milliliters of Type A blood will have a strong, immediate transfusion reaction that can lead to destruction of all the transfused RBCs or could even cause death. Type A cats should always receive type A blood. Type B cats should always receive type B blood. Type AB cats should receive type A blood (which is less likely to have circulating antiantibodies against the B antigen, and the A donors are more common). A-B incompatibility can also contribute to neonatal isoerythrolysis in cats when AB or A kittens receive anti-A antibodies in the colostrum of a Type B queen. Most cats carry an additional RBCs antigen called the Mik antigen. Those cats missing the Mik antigen may have naturally occurring alloantibodies to Mik-positive blood. Thus, a cat with Mik antigen-negative RBCs could demonstrate hemolytic transfusion reactions despite AB compatible blood. There are no patient-side tests for the Mik antigen so crossmatching is recommended. Equine blood types: In horses, there are 7 main blood group systems (A,C,D,K,P,Q,U) with greater than 30 red blood cell factors. Ca seems to be one of the most immunogenic antigens but may be less common. Horses are not born with alloantibodies. Blood type incompatibilities can contribute to neonatal isoerythrolysis (NI). NI may occur when the blood type of the mare is different than that of the stallion and the foal inherits the stallions sensitizing red blood cell type. The dam becomes sensitized to the antigen via placentitis, parturition or transfusion. Foals may receive anti-erythrocyte antibodies from the dam via colostrum, thus leading to hemolysis in the foal. Using Blood Typing Data Ideally, all dog and cat recipients should be blood typed prior to any blood product transfusion. Blood typing will help make better use of blood products. It will prevent A-B mismatch transfusion reactions in cats and will prevent sensitization of DEA 1 negative dogs with 1 positive blood. Blood typing can be done by all standard clinical pathology laboratories. In an emergency setting, however, it is usually more convenient to use patient-side blood typing kits. There are many ways to type blood (see document labeled “Blood Typing Tests”); the card type method and immunochromatography are most commonly used in practice. To type blood, the patient’s blood is mixed with anti-Ab that is present on the card or in the tubes. The samples are then examined for agglutination or an indicator line, which denotes the blood type. When typing, it is also important to look at the recipient blood for evidence of autoagglutination, which will disallow use of typing tests that have agglutination as the end point (cards, tubes). DEA 1 negative dogs should only be given negative blood products. DEA 1 positive blood products should only be given to positive dogs in order to prevent a DEA 1 negative dog from making antibodies against positive antigens. Positive dogs can receive positive or negative blood. In an emergency, dogs with an unknown blood type that have not received a previous transfusion can be given the “universal donor,” DEA 1 negative blood. Dogs that were transfused > 4-5 days ago should ideally be typed and crossmatched, too, because it usually takes 4-5 days before making antibodies to a transfusion. VETM 5291: Transfusion Medicine ALL cats should be blood typed prior to transfusion because giving the wrong type blood can be fatal. If feline blood typing is not available, a cross match is mandatory to rule out A-B incompatibility. A slide agglutination test with a drop of blood from donor and recipient is the minimum requirement in emergencies. Cats that were transfused >4-5 days ago should also be crossmatched. Most large animal (and exotic) recipients are not blood typed due to lack of patient point of care typing tests (except for 1 horse test for type Ca) and because there is usually only a donor or two available. In large animals, cross matching is largely used to assess compatibility but primarily in horses or animals that have received a previous transfusion. Species Blood types/groups Dog DEA 1 (most important), DEA 2-8, Best donor DEA 1 negative; Dogs do not Dal, Kai 1, Kai 2 have alloantibodies Cat A, B, AB, mik Need both A and B donors Horse A, C, D, K, P, Q, U and T Plus at least 30 blood factors Donkey Donkey factor Do not use to donate blood for horses Cattle A, B, C, F, J, L, M, R, S, T, Z Goats A, B, C, M, J Sheep A, B, C, D, M, R, X Ferret None Blood group systems A, B, C, D, E, H, Chicken I, J, K, L, N, P, and R. CROSSMATCHING Cross matching detects anti-RBC antibodies in the plasma of the donor or recipient. Crossmatch is typically only done for blood products that contain red cells. Having a compatible cross match reduces, but does not eliminate, the possibility of a transfusion reaction. Crossmatch also does not prevent sensitization to antigens which could cause reactions to future transfusions. To perform a major crossmatch, donor RBCs are mixed with recipient plasma. In a minor crossmatch, donor plasma is mixed with recipient RBCs. Some crossmatch procedures also recommend incubating at 4°F, 37°, and 42°F. Cross Match Recipient Donor R = Recipient D = Donor RBCs plasma Recipient whole blood Recipient Donor plasma RBCs VETM 5291: Transfusion Medicine Both major and minor crossmatches are evaluated for presence of autoagglutination or hemolysis. Crossmatches are graded on a scale from 0 to 4+, with Crossmatch Grade Meaning 0 No agglutination Trace Microscopic agglutination 1+ with small RBC aggregates admixed with free RBCs 2+ a few large agglutinates mixed with smaller clumps 3+ many large agglutinates 4+ one single large agglutinate with no free cells When doing a crossmatch, it is also important to do an autoagglutination screen with recipient blood and recipient plasma – this will identify autoagglutination which will make meaningful crossmatch difficult or impossible. Ideally, the donor blood chosen should be compatible by major and minor crossmatch. If none of the available blood is completely compatible, the least reactive blood with higher priority given to the major crossmatch should be used. The amount of plasma in the recipient is large in relation to the donor RBCs, so presence of incompatible antibodies could lead to destruction of the entire transfusion, thereby making it a “major” reaction. This is compared to administering a transfusion that is incompatible by minor crossmatch. In that case, there is relatively little donor plasma in a transfusion compared to the recipient RBCs, therefore, administering a transfusion that is incompatible by minor crossmatch (contains antibodies against the recipient RBCs) will only lead to a mild reaction. BLOOD PRODUCT ADMINISTRATION AND MONITORING After choosing the blood product and typing/crossmatching as appropriate, the transfusion should be prepared for administration. NO additional drugs or fluids should be added to the blood product prior to administration (the one exception is for pRBCs, some clinicians will sterilely add 0.9% NaCl to make the product less viscous). Blood should be given via a dedicated line. Mixing of different fluids in the same line or catheter could cause problems with the transfusion. For instance, 5% dextrose in water or other hypotonic solutions (0.45%NaCl) could cause hemolysis of the RBCs in the transfusion. Solutions containing calcium can inactive the anticoagulant and cause the transfusion to clot. Despite compatible blood type and crossmatch data, patients still must be monitored for possible reactions. To start, a physical examination is performed, and baseline heart rate, respiratory rate, and body temperature are noted. The VETM 5291: Transfusion Medicine transfusion is started very slowly and the animal is monitored for signs of reaction. Initially, the PE may be repeated every 5-10 minutes for the first 30 minutes. At each evaluation point, the transfusion rate is increased slightly if the patient has not shown signs of adverse reaction. If the heart or respiratory rates change significantly, if the body temperature changes by more than 1°C (2°F), or if any other clinical signs become evident such as hives, erythema, collapse, vomiting, or diarrhea, new colic, etc., a transfusion reaction should be suspected. Because blood products do not contain any preservatives, they should be promptly used after warming/thawing to prevent growth of bacteria. Most transfusions are given slowly over approximately 4-6 hours – this administration rate increases the likelihood a transfusion reaction will be identified while minimizing risk of bacterial growth. In the emergency setting, if an animal is close to death, blood products can be bolused or given as more rapid infusions. And in some settings, transfusions may need to be given more slowly (such as in heart failure). Care must be taken in choosing fluid pumps for administration of blood – some infusion pumps cause trauma to the RBCs and can lyse them due to excess pressure exerted as the blood passes through the cassette or tubing. It is important to ask the fluid pump representative about compatibility with blood transfusions. Blood can also be given via a standard gravity drip set without a pump. TRANSFUSION REACTIONS There are four major classes of transfusion reactions: acute immunologic, delayed immunologic, acute non-immunologic, and delayed non-immunologic transfusion reactions. Acute reactions happen during or within hours of the transfusion. Delayed reactions may happen days to years after the transfusion. Acute immunologic reactions The classic acute hemolytic transfusion reaction caused by antibodies and complement against donor RBCs is an example of an acute immunologic reaction. This is a type II hypersensitivity reaction. Clinical signs of acute hemolytic reactions may include lethargy, vomiting, diarrhea, fever, urticaria, facial swelling, restlessness, salivation, icterus, collapse, shock or death. Laboratory testing may reveal hemoglobinemia, hemoglobinuria, hyperbilirubinemia, bilirubinuria, and rapidly decreasing PCV. Blood transfusions should be discontinued immediately and supportive care, including fluid therapy, should be administered to ensure adequate perfusion. IgE mediated (Type I hypersensitivity) allergic reactions to blood may also occur. These manifest most commonly as erythema, urticaria (hives), and pruritus. Most are self-limiting or easily treated with diphenhydramine +/- corticosteroids. More significant anaphylactic reactions can also occur. Epinephrine, fluid therapy, oxygen supplementation, and vasopressors may be indicated to treat anaphylaxis. Nonhemolytic fever is the most commonly occurring acute immunologic reaction. Most fevers occur due to antibodies against donor white blood cells or VETM 5291: Transfusion Medicine platelets. These cells release inflammatory mediators, such as IL-1, IL-6, IL-8, and TNF alpha, during storage. These mediators are pyrogens. The longer the blood is stored, the more likely to have a febrile reaction. Most fevers are self- limiting and clinically insignificant. If a nonhemolytic fever is suspected, the transfusion should be slowed or stopped and care should be taken to rule out a more significant reaction. If fever is the only problem, the transfusion may be restarted at a lower rate. While some advocate diphenhydramine or NSAIDS, if not contraindicated, to treat significant fevers. This is probably of limited value as 1) this is not an IgE mediated reaction and 2) the NSAIDS may mask clinical signs (fever) which can signify a more significant reaction. Acute nonimmunologic transfusion reactions Most of the reactions in this category are related to storage/handling, administration or metabolic changes in response to the transfusion. They are not preventable with crossmatch or blood typing. Storage and warming of RBCs can deplete ATP stores and cause physical damage to RBC membranes, thereby making the cells more fragile. Acute nonimmunologic hemolysis can occur secondary to these physical membrane changes. Animals having a nonimmunologic hemolytic episode will have hemoglobinuria and hemoglobinemia in the absence of other systemic signs such as fever. Blood clots or air embolism can occur in the pulmonary vasculature if products are improperly administered. Transfusion of blood contaminated by bacteria or other microbes can also cause reactions. Clinical signs of animals receiving microbe contaminated blood can include vomiting, diarrhea, collapse, shock, and death, although some animals will not display these signs. Hypocalcemia may occur in large/multiple transfusions as a result of the citrate anticoagulant in the transfusions complexing with intravascular calcium. Hypocalcemia may manifest as tremors, tetany, seizures, bradycardia or ventricular arrhythmias, or facial pruritus (cat). Rarely, hyperkalemia can occur due to potassium leakage out of stored RBCs into the plasma portion of the transfusion. Finally, volume overload could occur if the patient has received too many fluids too quickly. Delayed immunologic reactions Delayed immunologic reactions include delayed hemolysis, transfusion-induced immunosuppression, and post transfusion thrombocytopenia. None of these are preventable with crossmatch or blood typing. Delayed immune mediated hemolysis can occur in animals that were previously sensitized to foreign RBC antigens and have only low levels of circulating antibody. Reexposure to the antigen triggers an anemnestic response and upregulation of antibody production, leading to hemolysis up to 2 weeks after transfusion. Immune mediated thrombocytopenia can occur 1-2 weeks after exposure to foreign platelet antigens in the transfusion. Delayed nonimmunologic transfusion reactions Blood-borne infections such as Babesia, Ehrlichia, Leishmania, Mycoplasma haemofelis (formerly Hemobartonella felis) FeLV or FIV are examples of delayed VETM 5291: Transfusion Medicine nonimmunologic reactions. Donor screening programs are imperative to reduce risk of such reactions. TRALI: transfusion related acute lung injury Defined as development of mild or severe ARDS within 6 hours or less of transfusion. It is thought to occur via the two-hit phenomenon. 1. Neutrophil sequestration and priming in the lung parenchyma. This is due to transfusion recipient factors such as endothelial injury. The neutrophils become primed by changing to a state in which they will react to an otherwise weak stimulus. 2. Neutrophil activation by a factor in the blood product. This can be antibodies directed against the recipient antigens or soluble factors such as bioactive lipids. The neutrophils release cytokines, reactive oxygen species and proteases. These products damage the pulmonary capillary endothelium. This damage ultimately causes inflammatory (non-cardiogenic/non-hydrostatic) pulmonary edema. Clinical signs include sudden onset of respiratory distress, tachycardia, hypoxemia, edema from the oral cavity or endotracheal tube, fever and hypotension. On radiographs this will appear as pulmonary infiltrates bilaterally with a normal heart size. Treatment involves immediately stopping the transfusion and treating supportively. TACO: transfusion associated circulatory overload Manifests as respiratory distress. It is more common in patients with renal insufficiency, a positive fluid balance, compromised cardiac function or rapid delivery of blood products. Clinical presentation is more like fluid overload than the inflammatory response of TRALI. The patient may have jugular venous distension, a previous history of CHF, or known systolic or diastolic dysfunction. Radiographs will be consistent with hydrostatic pulmonary edema. STORAGE LESION The “RBC storage lesion” refers to cumulative biochemical and biomechanical changes that occur in RBCs during storage that decrease their lifespan and function after transfusion. As red cells age, glucose in the bag of blood is consumed and levels of 2,3-diphosphoglycerate (DPG) and ATP decrease. These changes make the cells less deformable and more fragile. Recent studies suggest that transfusion of packed red blood cells (PRBCs) stored for >14 days is associated with increased rates of sepsis, multiple organ dysfunction, and mortality in human patients. Recent veterinary studies show that older blood products do not increase risk of mortality, except in dogs with IMHA in one of the studies. IMHA patients were also more likely to have transfusion reactions, primarily fever. Older products were also associated with development of hemolysis in any patient. Higher dose of blood product administered was also a risk factor for transfusion associated complications and in one study was a risk factor for nonsurvival. VETM 5291: Transfusion Medicine Blood Products and their uses Product Contains Indications Comments Fresh Whole RBCs Anemia for any reason, V & VIII gone in 24 hours, platelets blood clotting factors particularly due to gone within 6 hours, over time: Platelets Hemorrhage or decrease 2,3-DPG and increased Proteins Coagulopathy, commonly ammonia levels used in large animals and exotics where pRBCs are not available pRBCs Red cells Anemia Same boost in O2 carrying capacity in smaller volume, no clotting factors (tiny bit in residual plasma) Fresh Frozen Clotting factors Primarily for coagulopathy, All clotting factors, need 40-50 mL/kg Plasma proteins could be used to treat low to increase albumin by 1, assumes no albumin/protein ongoing loss (ie, not efficient for albumin replacement) Stored plasma Reduced amounts of Anticoagulant rodenticide not efficient for albumin replacement clotting factors (minus toxicity, possibly low V, VIII, vWF, plts) albumin proteins Platelet rich Clotting factors Thrombocytopenia, Generally does not contain enough plts plasma (PRP) Platelets coagulopathy to significantly elevate platelet count, not readily available, short shelf life Platelet Concentrated platelets Thrombocytopenia with Generally does not contain enough plts concentrate active life threatening to elevate platelet count, not readily hemorrhage, presurgical on available, short shelf life pt with low plts Cryoprecipitate vWF, factor VIII, Von Willebrands dz (to treat Does not contain significant quantities fibrinogen or bleeding or prevent of the other coag factors bleeding if given presurgery), hemophilia A, hypofibrinogenemia Hemoglobin Hemoglobin Anemia, hemorrhage, Currently unavailable. Risk for volume based oxygen incompatible transfusions, overload, alters ability to measure carriers (HBOC) no RBCs available, shock some clin path values, icterus, (eg, Oxyglobin) vomiting, diarrhea, death, monitor [Hb] Added info about blood products TYPES OF BLOOD PRODUCTS There are many different choices for blood products other than whole blood. Component therapy lets the clinician address the patient’s needs while limiting the VETM 5291: Transfusion Medicine number of foreign antigens to which the recipient is exposed. Component therapy also maximizes the number of patients that can be treated with a single donation. Red cell containing products Products containing red blood cells include fresh whole blood, stored whole blood, and packed red blood cells (pRBCs). These products are drawn from a donor and anticoagulated using either ACD (acid-citrate-dextrose) or CPDA-1 (citrate- phosphate-dextrose-adenine). Red cells have a storage life of 21 days in ACD and 35 days in CPDA. Use of red cell extenders increases storage life of red cell products to 42 days. Fresh whole blood is blood that has been administered within 6 hours of donation. It contains all the coagulation factors, active platelets, albumin and other plasma proteins as well as, of course, red cells. Stored whole blood is any whole blood that is greater than 6 hours old. It contains no active platelets and reduced coagulation factors, depending on its age. Whole blood is indicated for treatment of acute hemorrhage and anemic animals with concurrent coagulopathy or hypoproteinemia. We will sometimes use fresh whole blood for animals with hemorrhage accompanied by thrombocytopenia, although the product provides negligible platelets. A common starting dose is 20 mL/kg. Packed RBCs are made by centrifuging whole blood and decanting the plasma. This product contains only RBCs and negligible amounts of plasma needed to keep the product liquid. Indications for pRBCs are anemia of any sort, especially chronic or hemolytic anemias and for patients at risk for volume overload (eg, severe heart disease). Patients with liver disease should ideally receive pRBCs because pRBCs contain less citrate, adenine, ammonia and sodium compared to whole blood; storage time should also be short in patients with hepatic encephalopathy or severe liver disease because ammonia levels increased the longer the blood is stored. A starting dose is 10 mL/kg. A more accurate calculation is as follows: Volume to be administered (in Liters) = BV ×BW (kg) (PCVT – PCVP)/ PCVD. where BV is blood volume (90 mL/kg in dogs/horses, ruminants and 60 mL/kg in cats/camellids), PCVT is the desired/target PCV, PCVp is the PCV of the patient before transfusion, and PCVD is the PCV of the donor animal or unit of blood. The PCV of an average unit of pRBC is 65%, which can be used as an estimate in this equation if an exact measure is not available. Plasma Products Plasma is the non-red cell portion of blood. There are several types of plasma: fresh, fresh frozen, stored, frozen, cryoprecipitate, and platelet rich plasma. A standard starting dose for plasma is 10 mL/kg. Fresh plasma is taken off the RBCs within 3-4 hours and used within 6 hours of collection. It contains all factors including vonWillebrand factor, factor VIII, all the vitamin K dependent factors, antithrombin, an insignificant number of platelets, and other plasma proteins such as albumin. Fresh frozen plasma (FFP) is frozen at -70°C within 6 hours of collection. It contains all the same factors as fresh plasma except platelets. Storage life is 1 year, after which time it is considered frozen plasma. VETM 5291: Transfusion Medicine Fresh plasma and FFP are indicated for use in any coagulopathy, DIC, anticoagulant rodenticide toxicity, and inflammatory conditions such as SIRS/pancreatitis. They are not generally used for replacing proteins because the quantity required to increase the protein levels is often cost and volume prohibitive. Stored plasma is fresh plasma that has been refrigerated for up to 35d. It has reduced active coagulation factors and is especially useful as a source of Vitamin K dependent factors and plasma proteins. It contains no active platelets. Frozen plasma is plasma frozen after 6 hours of collection or FFP greater than 1 year of age. It is stored at -20°C and has a freezer life of 5 years. It primarily contains vitamin K dependent factors and other plasma proteins. Indications for stored and frozen plasma include anticoagulant rodenticide toxicity and possibly hypoproteinemia. Cryoprecipitate is derived by thawing FFP to between 0°-6°C and collecting the white precipitate that forms on the top of the sample. The leftover is cryo-poor plasma. Cryoprecipitate contains concentrated vonWillebrand’s factor, fibrinogen, and factors V, VIII, XIII and is used for deficiencies of these clotting factors. Dose is 1 mL / 10 kg. Platelet-rich plasma (PRP) or platelet concentrate are derived by centrifuging fresh whole blood at a slower rate than used to produce plasma. Platelets must be stored at 20-24°C, continuously agitated, and used within 6 hours. Dose of PRP is the platelets from one unit of whole blood per 10 kg body weight. Generally speaking, PRP is not worth the effort, expense, or use of donors for patients with non-life-threatening hemorrhage from thrombocytopenia. Platelets are rapidly consumed (especially in immune mediated thrombocytopenia cases) and large quantities of PRP are needed to demonstrably increase the platelet count. PRP is usually reserved for patients with severe thrombocytopenia that are either spontaneously hemorrhaging into vital organs (brain) or in need of an emergent surgical procedure. Lyophilized (freeze dried) platelets were recently introduced into the veterinary market. There is limited published data evaluating its efficacy at increasing platelet numbers or reducing hemorrhage in thrombocytopenic patients. References and Additional Reading 1) Blood Transfusions and blood substitutes in Dibartola, ed. Fluid Therapy in Small Animal Practice 4th ed. WB Saunders 2012, Philadelphia PA. 2) Giger U, Kilrain CG, Filippich LJ, Bell K. Frequencies of feline blood groups in the United States. J Am Vet Med Assoc 1989; 195:1230-1232. 3) Bracker K, Drellich S. Transfusion Reactions. Compendium on Cont Ed for the Pract Vet. 2005; 27(7): 500-511. 4) Wardrop JK, Reine N, Birkenheuer A, et al. Canine and feline blood donor screening for infectious disease. JVIM 2005. 19: 135-142. 5) Weinstein, et al. A Newly Recognized Blood Group in Domestic Shorthair Cats: The Mik Red Cell Antigen. J Vet Intern Med 2007; 21:287–292 VETM 5291: Transfusion Medicine 6) Blais, et al. Canine Dal Blood Type: A Red Cell Antigen Lacking in Some Dalmatians. J Vet Intern Med 2007; 21:281–286. 7) Hann L, Brown DC, King LG, and Callan MB. Effect of Duration of Packed Red Blood Cell Storage on Morbidity and Mortality in Dogs After Transfusion: 3,095 cases (2001–2010). JVIM 2014. 8) Holowaychuk M, Leader J, Monteith G. Risk factors for transfusion-associated complications and nonsurvival in dogs receiving packed red blood cell transfusions: 211 cases (2008–2011). J Am Vet Med Assoc 2014;244:431–437. 9) Semple JW, Rebetz J, Kapur R. Transfusion-associated circulatory overload and transfusion-related acute lung injury. Blood. 2019 Apr 25;133(17):1840-1853. 10) ACVIM Blood donor guidelines: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.13823 VETM 5291: Transfusion Medicine

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