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Transfusion Medicine Donna Oakley, CVT, VTS (ECC) University of Pennsylvania, School of Veterinary Medicine District of Columbia Academy of Veterinary Medicine
October 1, 2003 Schedule
Clinical Evaluation of a Bleeding Patient
When a patient presents with abnormal bleeding, it is important to determine the cause. Although it is the responsibility of the veterinarian to diagnose and choose an appropriate therapy for each patient, the veterinary nurse should be knowledgeable and anticipate the needs of the veterinarian and, most importantly, the patient. This requires a basic understanding of the physiology of hemostasis. Hemostasis Hemostasis, the body's balancing mechanism of arresting hemorrhage while simultaneously maintaining blood flow within the vascular compartment, occurs through a complex series of events involving the vessels, platelets, plasma coagulation factors, and the fibrinolytic system. The role that each component plays in hemostasis is dependent on the size of the vessel and the amount of damage that has occurred. Bleeding in smaller vessels may be controlled by a simple response involving the vasculature and platelets (e.g., normal wear and tear on capillaries), whereas incorporation of the plasma coagulation factors are necessary for hemorrhage control involving larger damaged vessels. The first response to blood vessel injury is vasoconstriction, which allows for diversion of blood flow around the injured area. Once the endothelial lining of the vessel is disrupted, the subendothelial connective tissue (i.e., collagen fibers) is exposed. Circulating platelets pool to the area of injury and, with the help of adhesive proteins like collagen, fibrinogen, fibronectin, and von Willebrand factor, adhere to the endothelial lining acting to arrest the initial episode of bleeding. This process is known as platelet adhesion. Once the platelets adhere to the subendothelium, they change shape and secrete certain biochemical substances that enhance platelet layering in the injured area (platelet aggregation). The platelets form a complete but unstable plug. This portion of the hemostatic process, involving the vasculature and platelets, is referred to as primary hemostasis and is usually adequate to stop bleeding in smaller vessels. With greater damage and/or larger vessels, secondary hemostasis involving plasma coagulation factors becomes necessary. Plasma coagulation factors are produced in the liver and circulate in the blood in the inactive form. They become activated only when exposed to certain substances (tissues or platelet phospholipids). Initiation of the extrinsic and intrinsic clotting pathways leads to subsequent activation of all factors in a cascade-like effect, converging in a common pathway. Tissue thromboplastin, released from the injured vessel wall, initiates the extrinsic clotting pathway. This is an extravascular process in that tissue thromboplastin is not normally found in blood and must gain entry to the vascular system. Clotting via the intrinsic pathway begins when blood comes into contact with a foreign substance or surface (i.e., damaged endothelium). Activated platelets release a phospholipid allowing coagulation factors in this pathway to activate one another. In the intrinsic pathway, all factors necessary for clot formation are within the circulating blood and, therefore, this is an intravascular process. The end result of this clotting cascade is the creation of fibrin, a threadlike protein. The fibrin threads form an insoluble meshwork over the site of the platelet plug, consolidating and stabilizing the clot. **For simplicity of presentation, the pathways have been reviewed as divided processes. The reader must realize that classic cascade presentation of fibrin formation has many underlying complexities and interrelationships that go beyond the scope of this paper. The fourth and final step in the hemostatic process is fibrinolysis. Once the vessel is healed, fibrinolytic enzymes digest the clot that has been formed, restoring normal blood flow. Clot lysis produces small pieces of fibrin, referred to as fibrin split products (FSPs) (or fibrin degradation products {FDPs}), which are cleared from circulation by the liver. Small levels of FSPs always appear in the circulation as a result of bleeding and clotting secondary to normal wear-and-tear on vessels. FSP levels increase during episodes of excessive bleeding with diffuse coagulation (i.e., disseminated intravascular coagulation {DIC}) and in patients with compromised liver function. Following clot digestion, vessel wall endothelium is reestablished and returned to its original state. Clinical assessment An accurate history, thorough physical exam, and certain laboratory tests must be performed in order to properly evaluate a bleeding patient, determine a diagnosis, and define a therapeutic plan. History A complete history is critical in beginning a work-up for a hemostatic defect. In veterinary medicine, all pertinent information regarding patient history must be gathered from the owners. Obtaining and assessing a complete and detailed history will help define the nature, severity, and duration of clinical signs and aid in making a correct diagnosis. This attention to detail allows the clinician to establish probability for each possible differential early in the diagnostic process. Questions should be very clear and thought provoking. Devising a list of questions for owners to review will hopefully help stimulate them to think of some very important, most likely not obvious facts. Does the animal have any previously diagnosed diseases? Is the animal currently on any medication? A list of any prescription or over-the-counter medications should be included as many drugs have potentially harmful or complicating side effects, resulting in a toxic effect on red blood cells, white blood cells, and platelets. Complete vaccination history should not be overlooked as a relationship between recent vaccination and onset of immune-mediated hemolytic anemia (IMHA) has been questioned. The animal's environmental history may suggest potential exposure to toxic or organic substances such as anticoagulant rodenticide poisons or lead. Tick exposure should also be investigated. It is vital to evaluate the current bleeding episode and characterize the bleed as localized or multifocal. Is this the animal's first bleeding episode, or is there a history of bleeding tendency? These facts may help differentiate between an acquired or hereditary disorder. Specific breeds may suggest specific coagulopathies. Any information the owner may have regarding breed history could provide helpful clues. Many breeders are increasingly educated regarding bleeding disorders affecting their pets' breed and, specifically, their pet's lineage. Physical exam A complete physical examination and multiple monitoring procedures may be required to properly assess the patient in a bleeding crisis. Optimal assessment cannot be based on the result of a single parameter, but is based on the results of several physical exam findings and monitored parameters which should always be evaluated in relation to one another. Certain clinical signs found on physical exam may help determine the origin of the bleeding episode. Small surface bleeds (e.g., petechiation, ecchymosis, epistaxis, hematuria) are usually suggestive of platelet or vascular abnormalities. Larger bleeds or bleeding into body cavities (e.g., hematoma formation, hemarthroses, deep muscle hemorrhage) are suggestive of clotting factor deficiencies. A combination of these clinical signs is not uncommon. In anemic patients, the development and progression of clinical signs depends on the rapidity of onset, degree, and cause of anemia, as well as the animal's physical activity. Common physical findings are those associated with a decrease in red cell mass: lethargy, weakness, pale mucous membranes, tachycardia, tachypnea, and bounding pulses. The cardiovascular and respiratory system should be carefully evaluated. Assessment of perfusion is based on mucous membrane color, capillary refill time (CRT), heart rate, and pulse rate, strength, and character. In a severe anemic state, a low-grade systolic flow murmur may occur secondary to decreased blood viscosity. Mucous membrane color can be used to monitor the patient's response to therapy or indicate the development of a problem. Prolonged CRT is suggestive of compromised tissue perfusion and shock, but may be difficult to assess in an anemic patient. Weak and rapid pulses suggest severe dehydration and poor perfusion; bounding pulses suggest anemia. Assessment of respiratory rate and effort, as well as careful auscultation, may help differentiate between decreased oxygen carrying capability and possible pulmonary thromboembolism. Monitoring all parameters in unison with one another will lend information regarding bleed severity and potentially life-threatening complications. Patients should be evaluated for signs of underlying or concurrent disease. Especially, dogs with IMHA should be carefully examined for signs of other immune-mediated disease, such as concurrent immune-mediated thrombocytopenia (IMT) (i.e., Evans syndrome). If petechiation is present, IMT or other coagulopathies, such as liver disease or disseminated intravascular coagulation (DIC), should be investigated. Other common physical findings in dogs presenting with hemolytic disease are those relating to an accumulation of bilirubin, hemoglobin, or both, in blood, urine and soft tissue. As a result of extravascular red blood cell destruction, increased quantities of bilirubin are presented to the liver for conjugation and excretion. Bilirubin begins to accumulate in blood, urine, and soft tissue when the quantity of bilirubin present exceeds the livers capacity to excrete it in the bile. Consequently, dogs with severe extravascular hemolysis present with icterus and pigmenturia caused by the presence of bilirubin or hemoglobin in the urine. Given the low threshold for urinary excretion of conjugated bilirubin in dogs, bilirubinuria develops early in the disease process and precedes hyperbilirubinemia and icterus. Icterus is best recognized on the gingiva, sclera, conjunctiva, and inner pinnae, but can be seen on all skin surfaces when severe. If intravascular hemolysis occurs, hemoglobinemia with or without hemoglobinuria may be present. Laboratory tests Although information obtained from the history and specific clinical signs may suggest a diagnosis, certain laboratory tests are necessary for definitive diagnosis. Laboratory tests should be performed ASAP and therapy instituted promptly after test samples are obtained. Serial hematocrit determinations may help demonstrate progression or stabilization of bleeding, taking into account the body takes a certain amount of time to equilibrate following an acute bleeding episode. Anemia is suggested when one or more of the red cell parameters are below normal for the age, sex and breed of the species concerned. Of these parameters, PCV provides a simple, quick, and accurate means of detecting anemia, and allows classification as mild, moderate, or severe. Dehydration and splenic contraction may mask anemia, whereas hemodilution may cause a temporary reduction in red cell parameters. Evaluating both PCV and total plasma protein (TPP) levels may help in differentiating these variables. Dehydration is associated with increases in both PCV and TPP, while with splenic contraction only PCV elevation is seen. Decreases in both PCV and TPP are associated with hemodilution following acute blood loss or fluid therapy, whereas a reduction in PCV only is usually associated with hemolytic anemias. Total plasma protein is most often normal in anemia secondary to decreased production or increased destruction of erythrocytes, compared with blood loss, where both PCV and TPP may be decreased due to loss of erythrocytes and plasma proteins, and compensatory shift of fluid from the interstitial space to the intravascular compartment. The degree of anemia varies with the nature, extent, and duration of the disease process. Normal platelet count is 150,000-400,000/ul. Abnormal bleeding may occur with platelet counts below 40,000/ul, although each patient varies and some animals may not exhibit clinical signs associated with bleeding with a platelet count of 2,000/ul. The thrombocytopenic patient requires special care (i.e., extra cage padding, avoidance of central vessels for blood collection, extended application of pressure to venipuncture sites). In an animal exhibiting signs of surface bleeding with a normal platelet count, consideration should be given to the function of the platelets. Certain tests are available to monitor coagulation in patients with suspected coagulopathies. Prothrombin time (PT) measures extrinsic and common clotting pathway activity, whereas activated partial thromboplastin time (aPTT) measures intrinsic and common pathway activity. Prolongation of PT/aPTT will be seen when clotting factors are depleted below 30% of normal. PT and aPTT samples must be collected and processed carefully to avoid potential sample errors. Atraumatic venipuncture and smooth blood flow into collection tubes are necessary to avoid extraneous clotting mechanism activation. Samples should be processed immediately after collection and frozen if being sent to an outside laboratory. Elevation in FSPs occurs with excessive bleeding and fibrinolysis, and in animals with severe liver dysfunction. Interpreted in conjunction with the PT, aPTT, and platelet count, elevated FSP levels are useful as a diagnostic indicator of DIC. Practical hemostatic tests The following are simple, in-house tests requiring no specialized equipment. They are quick, inexpensive, practical tests that allow recognition and characterization of hemostatic defects. These tests are often referred to as "cage-side", in that they provide results almost immediately. Platelet estimation A quick, reasonably accurate estimation of platelet numbers can be made from a stained blood smear is much quicker than an actual platelet count. After routine preparation and staining, the blood smear is scanned to ensure even platelet distribution and that there is no evidence of platelet clumping. The average number of platelets in approximately 5-10 oil immersion fields is counted to estimate platelet numbers. The count is ranked as very low, low, normal, or high. One platelet per oil-immersion field represents approximately 20,000 platelets. Approximately 8-12 platelets per oil-immersion field are considered normal. While platelet estimation helps determine the presence of thrombocytopenia in an emergency situation, a true platelet count is necessary to classify the severity of depletion. Ongoing platelet quantitation is helpful in monitoring the course of a disease or the patient's response to certain therapies. Bleeding time tests Bleeding time is the time it takes for bleeding to stop after severing a vessel. The two types of bleeding time tests most often used in veterinary medicine today are buccal mucosal bleeding time (BMBT) and cuticle bleeding time (CBT). The BMBT assesses platelet and vascular contribution to hemostasis, thereby evaluating primary hemostasis. A disposable template with two spring-loaded blades is used to produce standardized incisions in the buccal mucosal surface of the upper lip. The blades create 5mm long X 1 mm deep incisions. The duration of bleeding from these incisions is monitored. Buccal Mucosal Bleeding Time Materials: Procedure:
The CBT is another bleeding time test. The CBT is useful for evaluating overall hemostasis. It is sensitive to defects in vascular integrity, platelet function, and coagulation. Cuticle Bleeding Time Materials: Procedure:
Activated clotting time The activated clotting time (ACT) is a simple, inexpensive screening test for severe abnormalities in the intrinsic and common pathways of the clotting cascade. It evaluates the same pathways as aPTT. Some argue that ACT is less sensitive at detecting factor deficiencies than aPTT in that factors must be decreased to less than 5% of normal in order to prolong ACT, whereas the aPTT will be prolonged with factor deficiency less than 30% normal. Activated Clotting Time Test
Materials: Procedure:
Small Animal Transfusion Medicine:
Blood Collection, Storage and Administration As a result of the increased specialization in veterinary medicine today, the demand for blood products has risen dramatically. These specialties (i.e., emergency medicine, critical care, oncology) have created a need for knowledge and application of that knowledge in veterinary transfusion medicine and, therefore, transfusion medicine has become a specialty unto itself. The importance of transfusion education for veterinarians, veterinary nurses, and students continues to unfold and is clearly the link to ensuring the overall quality of all aspects of blood banking and transfusion services. A safe and adequate supply of blood components for transfusion is indispensable. Blood sources
Historically, veterinarians have relied on donor dogs living within the hospital facility as a source of blood for transfusion purposes. Blood was collected for immediate use, and little emphasis was placed on quality control. These few in-house donors failed to meet the growing need for transfusion. During the past few years, university-based blood donor programs, as well as several commercial animal blood banks, have been established to help meet blood transfusion needs. These facilities supply safe and high quality blood products that are processed according to the standards set forth by the American Association of Blood Banks (AABB). Blood banking staff also share expertise in transfusion medicine through newsletters and individual case consultation requests. Purchasing products from these blood banks and maintaining an inventory within the hospital may be much more time efficient and cost-effective than maintaining in-house donors and likely provides a better product. Large blood banks obtain their supply from either a closed donor colony or a volunteer donor program. There are advantages and disadvantages to each approach. Closed donor colonies may be supported by animals that have been rescued from terminal situations (i.e., retired racing dogs, SPCA). These animals are given a second chance at life and are adopted into homes following a predetermined stay at the blood bank facility. Although they may originate from less than optimal homes, they are provided with excellent health maintenance as a result of their closed colony environment. Other blood banks have opted to establish volunteer donor programs to meet the transfusion needs of the profession. Recruitment of donors is accomplished through employee personal pets, healthy client-owned animals, breeders, and organized dog clubs. Client education on the importance of blood product availability and the need for blood donors is instrumental in establishing a large donor pool. Informed and educated pet owners are a valuable asset to this type of program. Most are willing to volunteer their animal for periodic blood donation (i.e., 3-4 times yearly) once they understand the need for blood products and the elements of the donation process. Comparable to human blood donor programs, these people are motivated by altruism. Nevertheless, potential donors may carry illnesses that could possibly affect the safety of the donation process as well as the safety and quality of the blood products, thereby further compromising the patient. For this reason, it is important to verify donor health status through a brief history, physical exam, and appropriate laboratory testing, all of which are performed on the day of the donation. There are specific requirements canine donors must meet before being accepted into a blood donor program. Donors must be a minimum of one year of age and weigh at least 25 kilograms to allow for the collection of a full unit (i.e., 450 ml +/- 10%). They must be healthy, have a current vaccination status for distemper, hepatitis, parainfluenza, parvovirus, and rabies, and not be on medication at the time of donation (excluding heartworm and flea preventative). As canine donors are not sedated for blood collection, good temperament is required for successful donation. On an annual basis, a complete blood count, chemistry profile, and testing for geographically specific infectious agents (e.g. Ehrlichia canis, Babesia canis, Dirofilariasis immitis) must be performed. In addition, the hematocrit or hemoglobin concentration should be at least >40% or >13.5 gm/dl, respectively, prior to each donation. Donors can be screened for vonWillebrand factor antigen levels to identify the population of the donor pool that has the highest plasma concentration of this platelet adhesion protein for use in patients with von Willebrand disease. Blood donor dogs should be typed for DEA 1.1, and possibly others (DEA 1.2 and 7). The most severe antigen-antibody reaction is seen with these antigens, most specifically DEA 1.1. Dogs that are negative for DEA1.1 are considered universal donors. Significant naturally occurring alloantibodies are not seen in the dog, therefore, antigen-antibody reactions are not likely to occur on initial transfusion. However, dogs that are DEA 1.1, 1.2, and 7 negative can develop alloantibodies to DEA 1.1, 1.2, and 7 from a mismatched transfusion. This can occur within 4-14 days from initial transfusion. These antibodies can potentially destroy the donor's red blood cells (i.e., delayed hemolytic transfusion reaction), ultimately minimizing the benefits of the transfusion. The approach to the feline donor is much more complicated than its canine counterpart. At present, there are few commercial feline blood banks. In addition, volunteer programs for cats hold many risks. Although dogs will donate blood voluntarily, the majority of cats must be sedated for blood donation purposes. The legal ramifications associated with sedating personal pets for blood donation purposes is far too great. Another concern is that cats can harbor infectious agents more readily than dogs, requiring that exclusively indoor only cats be used. Feline blood donors should be good-natured young adults with short hair, allowing for easier vascular access. They should be large and lean, weighing at least 4 kilograms. Good health can be verified through history, physical exam, and routine laboratory testing. Donors must have current vaccination status for rhinotracheitis, calicivirus, panleukopenia, and rabies. Annual laboratory screening includes: complete blood count, serum biochemistry profile, feline leukemia virus, feline immunodeficiency virus, feline infectious peritonitis, and Haemobartonella felis. Prior to each donation, donor hematocrit (>35%) or hemoglobin (>11 gm/dl) is checked. One blood group system, the AB system, has been recognized in the cat. It contains three blood types: A, B, and the extremely rare AB. These blood types represent antigens, or protein markers, on the surface of the red blood cell. Nearly all domestic short hair (DSH) and domestic long hair (DLH) cats have type A blood, thereby making it the most common blood type. Many purebred cats (and some DSHs) have been identified with type B blood. The proportion of A and B type varies not only among the different breeds, but also nationally and internationally. Cats differ from dogs in that they have significant, naturally occurring alloantibodies against the other blood type. Cats with type B blood have very strong naturally occurring anti-A alloantibodies, whereas type A cats have relatively weak anti-B alloantibodies. Because of the presence of naturally occurring alloantibodies, there is no universal blood type in the cat. All feline blood donors and recipients must be blood typed, and only typed, matched blood should be administered. The extremely rare blood type-AB cat can be safely transfused with type-A blood. Blood collection
Blood collection systems Quality should be the primary goal in the collection, processing, storage and administration of all blood products. At each step, it is crucial that practices must prevent or delay adverse changes to blood constituents, and minimize bacterial contamination and proliferation. Many improvements in the preparation of components from whole blood have been described. Whole blood is most often collected into commercially available plastic bags (Baxter Healthcare Corporation, Fenwal Division; Miles, Inc., Cutter Biological Division, Elkhart, IN; Terumo Medical Corporation, Somerset, NJ). These sterile bags are considered "closed" collection systems in that they allow for collection, processing, and storage of blood and blood components without exposure to the environment, therefore diminishing the risk of bacterial contamination to the product. These systems are available in a variety of configurations that will determine blood component preparation and storage. They all meet human blood banking standards and have been tested successfully in veterinary medicine. A single blood collection bag is used for the collection of whole blood when it is to be administered as whole blood. It consists of a main collection bag containing anticoagulant- preservative solution and integral tubing with a 16-gauge needle attached. This system is not recommended for component preparation in that the bag must be entered in order to harvest components, risking environmental exposure and potential bacterial contamination. If the bag is entered, the definition of this system then becomes "open", and the product must be used within a 24-hour period. Other collection systems consist of a primary collection bag containing anticoagulant- preservative solution and one, two, or three satellite bags intended for component preparation. One of the satellite bags may contain 100 ml of an additive solution used for red cell reconstitution following plasma removal. Additive solutions (i.e., saline, dextrose, adenine) extend pRBC storage time. Vacuum glass bottles containing ACD anticoagulant-preservative solution have been the most popular collection system used in veterinary medicine. Although blood collection is easier with this system, there are many limitations and disadvantages: this is considered an "open" collection system, the glass activates platelets and certain clotting factors, the foam created during collection will disrupt the red cell surface and cause hemolysis, and component preparation is not possible. For these reasons, vacuum glass bottles are not recommended. Vacuum chambers that allow for more rapid collection into blood collection bags are available. Anticoagulant-preservative solutions There are several anticoagulants, anticoagulant-preservatives, and additive solutions available for blood collection for transfusion purposes. The primary goal of preservative solutions is to maintain red cell viability during storage and to lengthen the survival of red cells post transfusion. According to AABB standards, seventy-five percent of transfused red blood cells must survive for 24 hours following infusion in order for the transfusion to be considered acceptable and successful. The longer cells are stored, the more viability decreases. Predetermined storage times are based on studies that have investigated adverse biochemical changes that take place during red cell storage. These changes, referred to as the "storage lesion", include a decrease in ATP, pH, and 2,3-DPG (increasing hemoglobin-oxygen affinity) and an increase in lactic acid. All of these ultimately lead to a loss of red cell function and decreased viability. Storage time will vary with the anticoagulant- preservative solution used:
Whole blood and blood components With the availability of variable speed, temperature-controlled centrifuges and the advent of plastic storage bags with integral tubing for collection, processing, and administration, specific blood component therapy is possible. The goal in veterinary transfusion medicine is to limit whole blood transfusion and to use component therapy whenever possible. Whole blood can be stored or processed into one or more of the following components: red blood cells, platelets, plasma, and cryoprecipitate. Blood components permit specific replacement therapy for specific disorders, reduce the number of transfusion reactions as a result of diminished exposure to foreign material, and decrease the amount of time needed to transfuse. Most importantly, appropriate therapeutic use of blood components increases the number of patients who benefit from this limited resource. Blood is comprised of two portions: a cellular portion and the plasma, which acts as a carrier medium for the cells, proteins, gases, nutrients, vitamins, and waste products. Each component of blood has a specific role or function in the body. Certain disease states will require replacement of one or any combination of these components. The component(s) chosen will depend on the needs of the patient. Initial collection yields fresh whole blood (FWB) and is defined as such for up to 8 hours after collection. FWB provides red blood cells, white blood cells, platelets, plasma proteins, and coagulation factors. Certain components in blood are more fragile than others and will become less effective with time and ambient temperature change. For example, platelet and coagulation factor efficacy becomes questionable once whole blood is refrigerated. In order to achieve full benefit of all components when needed, FWB should be administered immediately following collection. FWB is used in actively bleeding, anemic animals with thrombocytopenia and/or thrombocytopathia, anemia with coagulopathies, disseminated intravascular coagulation (DIC) and massive hemorrhage. In cases of severe hemorrhage, administration of all components may be necessary to support the patient. Massive hemorrhage is defined as a loss approaching or exceeding one total blood volume within a 24-hour period. Following collection, whole blood must be processed into components or at least refrigerated at 1-6° C within 8 hours. After 24-hour storage of whole blood, platelet function is lost and the concentration of labile coagulation factors decreases. The product is then defined as stored whole blood (SWB) and provides RBCs and the plasma protein albumin. The length of time a unit of whole blood can be stored under refrigeration is dependent on the anticoagulant-preservative solution used in collection. With the advantages in the use of blood components so well documented in both human and veterinary medicine and the improved availability of these products as a result of commercial blood banks, the use of whole blood is no longer considered the treatment of choice. However, SWB can be used in patients that require intravascular volume expansion as well as oxygen-carrying support. The use of whole blood, fresh or stored, is not recommended in severe chronic anemia. Chronically anemic patients may have a reduced red cell mass but have compensated over time by increasing their plasma volume to meet their total blood volume. Administration of whole blood may expose these patients to the risk of volume overload, especially in patients with preexisting cardiac disease or renal compromise. Packed red blood cells (pRBC) is the component of choice for increasing red cell mass in patients who require oxygen-carrying support. Decreased red cell mass may be caused by decreased bone marrow production, increased destruction, or surgical or traumatic bleeding. Although it seems logical that blood loss should be replaced with whole blood, replacing blood volume with pRBC and crystalloid or colloid solutions adequately treats most blood loss. This is often adequate therapy for the majority of acutely bleeding patients. Transfusion of pRBC is not recommended in patients who are well compensated for their anemia (e.g., chronic renal failure). The decision to perform red cell transfusion should never be based solely on hematocrit or hemoglobin levels. Patients should be properly evaluated and pRBC administration based primarily on clinical status (e.g., tachycardia, poor pulse quality, lethargy). Platelet-rich plasma (PRP) is harvested from a unit of FWB that is less than 8 hours old and has not been cooled below 20-24° C. Refrigerated platelets do not maintain function or viability as well as platelets stored at room temperature. The PRP may be administered following centrifugation, or the platelets may be concentrated by further centrifugation and removal of most of the supernatant plasma. Under optimal conditions, platelets prepared from a single unit of FWB administered to a 30 kg dog would be expected to result in an increase in the patient's platelet count of 10,000/_l. The major indication for platelet transfusion is to stop severe, uncontrolled or life-threatening bleeding in patients with decreased platelet number and/or function. Patients experiencing massive hemorrhage may require platelet support to compensate for excessive consumption during hemostasis and the dilution factor associated with volume replacement therapy. In veterinary medicine, platelet preparation is difficult due to the large volume needed in order to measurably increase platelet numbers in larger dogs. In some patients, however, cessation of bleeding following platelet transfusion has been achieved without a measurable increase in platelet number. Due to the impracticality associated with production of this component in the required volume necessary for significant impact, specific storage requirements, and the short shelf life, in veterinary medicine we routinely treat thrombocytopenia and/or thromobcytopathia with active bleeding with FWB through which the patient will receive both platelets and oxygen-carrying support. In situations of platelet destruction, such as idiopathic thrombocytopenia purpura (ITP), the survival of transfused platelets is a matter of minutes rather than days, yet platelet transfusion may still be warranted if the patient is acutely bleeding into a vital structure (i.e., brain, myocardium, lung). In addition to water and electrolytes, plasma contains albumin, globulins, coagulation factors and other proteins. Plasma is primarily used for its coagulation factor value; it does not contain functional platelets. Most coagulation proteins are stable at 1-6° C, with the exception of factors V and VIII. In order to maintain adequate levels of all factors, plasma must be harvested from a unit of whole blood and frozen at - 18° C or below within 8 hours from the time of initial collection. This product is referred to as fresh frozen plasma (FFP). FFP will retain its coagulation factor efficacy for a period of 12 months provided it is maintained at the appropriate temperature. FFP can be used to treat most coagulation factor deficiencies (e.g. DIC, liver disease, anticoagulant rodenticide toxicity) and other conditions (e.g., pancreatitis). FFP is not recommended for use as a blood volume expander or for protein replacement in animals with chronic hypoproteinemia. If FFP is not used within 12 months, it can be relabeled as frozen plasma (FP) and stored for an additional 4 years. Also, plasma may be separated from a unit of whole blood at anytime during storage. When stored at -18° C or less, this component is called FP and may be kept for up to 5 years. If not frozen, it is called liquid plasma (LP) and has a shelf life not exceeding 5 days following the expiration date of the WB from which it was harvested. Plasma prepared from outdated WB may have higher levels of ammonia than FFP as a result of longer contact with red cells prior to its preparation. FP and LP may have varying levels of the more stable coagulation factors, as well as albumin, but they do not contain functional platelets or the labile coagulation factors V and VIII. FP and LP can be used to treat stable clotting factor deficiencies and certain cases of acute hypoproteinemia (i.e. parvoviral enteritis). If animals are severely or chronically protein deficient, plasma must be administered in large volumes in order to have a measurable impact in managing the acute effects of hypoproteinemia (i.e., pulmonary edema, pleural effusion). In this case, synthetic colloid solutions should be considered since they are readily available and more effective in increasing oncotic pressure. As with FFP, FP and LP are not recommended for use as a blood volume expander. Cryoprecipitate (CRYO) is the cold-insoluble portion of plasma that precipitates after FFP has been slowly thawed at 1-6° C (in a refrigerator). The precipitated material contains concentrated amounts of von Willebrand factor (vWF), factor VIII:C, fibrinogen, and fibronectin. Following production, cryoprecipitate can be frozen at -18° C or colder and has a shelf life of one year from the original date of whole blood collection. CRYO can be used in patients with suspected or diagnosed von Willebrand disease (vWD), hemophilia A, or fibrinogen deficiency. Each unit of CRYO contains approximately 25-50 ml of liquid plasma. Blood administration Ideally, patients should be blood-typed and crossmatched prior to any blood transfusion. If blood typing reagents or cards are not available, at the very least a blood cross match (BCM) test should be done. Blood typing determines the blood group antigens on the surface of the red blood cell. A BCM test detects any serum (plasma) incompatibility between donor and recipient. If there is evidence of macroscopic agglutination of the patient's blood (rarely seen in cats) or severe hemolysis of the patient's blood sample, a BCM test cannot not be performed. Refrigerated blood may be gently warmed by allowing it to sit at room temperature for approximately 30 minutes. Properly administered cold blood will not increase the chance of a transfusion reaction, but, large amounts of cold blood given at a rapid rate can induce hypothermia and cardiac arrhythmias. Routine warming of red cell products is not recommended except in neonates, hypothermic patients, and with massive transfusion. Several types of blood warmers are commercially available. In an emergency situation, the tubing of the administration set can be placed in a warm water bath, not to exceed 37° C, so that warming can occur as blood passes through the tubing. The entire unit should not be immersed in the bath. Frozen products should also be thawed in a 37° C warm water bath. No blood product should be exposed to temperatures exceeding 42° C as this results in damage to red blood cells and denaturation of blood proteins. Warming red cell products or thawing plasma products in a microwave oven is not recommended unless it is an AABB approved microwave. The aim of transfusion in the anemic patient is not to return the packed cell volume to normal values, but to correct the clinical signs. The volume of blood administered is dependent on the onset and degree of anemia, clinical status of the patient, and body weight. Clinical evaluation of the patient post-transfusion will determine if further blood product support is necessary. Whole blood and blood component administration volume
Administration rates are variable. For example, a patient with massive hemorrhage may require a more rapid transfusion than a normovolemic patient with a chronic anemia. Blood should not be administered at a rate exceeding 22 ml/kg/hr. However, rate is less critical in a hypovolemic animal than a normovolemic animal where circulatory overload is a potential problem. Cardiovascularly compromised animals cannot tolerate infusion rates that exceed 4ml/kg/hr. It is recommended for all patients that blood components be infused slowly (e.g., 1 ml/kg) for the first 10-15 minutes while closely observing for signs of an acute transfusion reaction. The blood product should then be infused as quickly as will be tolerated, but should not take longer than four hours. Before infusion, baseline values of attitude, rectal temperature, pulse rate and quality, respiratory rate and character, mucous membrane color, capillary refill time, hematocrit, total plasma protein and plasma and urine color should be monitored. The majority of these parameters should be checked every 30 minutes during transfusion and evaluated routinely post-transfusion to ensure the desired effect has been achieved. Transfusion reactions
Animals should be carefully monitored for any adverse reactions during and for several weeks following transfusion. Transfusion reactions can be classified as immune-mediated or nonimmune-mediated in origin. Immune-mediated transfusion reactions can be hemolytic, with either acute (due to preexisting alloantibodies or prior sensitization) or delayed (can be exhibited 2-21 days post transfusion) presentation. Hemolytic transfusion reactions are the most serious, but are the most rare. In acute situations, intravascular hemolysis is due to preexisting antibodies and clinical signs include, but are not limited to, fever, tachycardia, weakness, muscle tremors, vomiting, collapse, hemoglobinemia and hemoglobinuria. The most common hemolytic transfusion reaction is delayed in presentation and can be recognized clinically as an unexplained decrease in hematocrit. Sensitization can occur as a result of a mismatched transfusion for up to 21 days as antibodies are produced, resulting in hemolysis. Nonhemolytic transfusion reactions are a result of antibodies to white blood cells, platelets, or plasma proteins. These reactions are most often transient in nature, and do not cause life threatening situations. Clinical signs include anaphylaxis, urticaria, pruritus, pyrexia, and neurologic signs. Vomiting can be noted with any type of transfusion reaction, therefore, patients receiving blood products should be fasted prior to administration. There are a variety of factors associated with nonimmune-mediated transfusion reactions. Any type of trauma to the red blood cells will potentially cause hemolysis: 1)overheating red cell products (which also causes protein denaturation and may increase bacterial growth during infusion), 2) freezing of red cell products, 3) mixing red blood cell products with nonisotonic solutions may cause cellular damage, 4) warming and then rechilling, and 5) collecting or infusing blood through small needles or catheters. Bacterial pyrogens and sepsis can be a complication of improperly collected and stored blood. Dark brown to black supernatant plasma in stored blood indicates digested hemoglobin from bacterial growth. Any blood with discolored supernatant should be immediately discarded. Citrate intoxication may occur when citrate:blood volume ratio is disproportionate or in massively transfused patients, particularly in those with liver dysfunction. This compromised state can be confirmed by obtaining an ionized serum calcium. It is imperative to administer the appropriate volume of blood to each patient. Specific component therapy should be utilized to treat each disorder and the patient's cardiovascular status should always be assessed prior to determining required volume and administration rate. Given that blood is a colloid solution, vascular overload is a potential complication. All blood products should be filtered in order to help prevent thromboembolic complications. Standard blood infusion sets have in-line filters with a pore size of approximately 170-260 microns. A filter of this size will trap cells, cellular debris, and coagulated protein. Trapped debris in combination with room temperature conditions may promote proliferation of any bacteria that may be present; therefore, blood infusion sets may be used for several units of blood products or for a maximum time of 4 hours. Micoraggregate filter systems with a pore size of 20-40 microns may be used for routine low-volume transfusion (i.e., <50 ml whole blood, <25 ml pRBC or plasma). |
