Controversies related to red blood cell transfusion in critically ill patients

Objective – To review the evolution of and controversies associated with allogenic blood transfusion in critically ill patients. Data sources – Veterinary and human literature review. Human Data Synthesis – RBC transfusion practices for ICU patients have come under scrutiny in the last 2 decades. Human trials have demonstrated relative tolerance to severe, euvolemic anemia and a significant outcome advantage following implementation of more restricted transfusion therapy. Investigators question the ability of RBCs stored longer than 2 weeks to improve tissue oxygenation, and theorize that both age and proinflammatory or immunomodulating effects of transfused cells may limit efficacy and contribute to increased patient morbidity and mortality. Also controversial is the ability of pre‐ and post‐storage leukoreduction of RBCs to mitigate adverse transfusion‐related events. Veterinary Data Synthesis – While there are several studies evaluating the transfusion trigger, the RBC storage lesion and transfusion‐related immunomodulation in experimental animal models, there is little research pertaining to clinical veterinary patients. Conclusions – RBC transfusion is unequivocally indicated for treatment of anemic hypoxia. However, critical hemoglobin or Hct below which all critically ill patients require transfusion has not been established and there are inherent risks associated with allogenic blood transfusion. Clinical trials designed to evaluate the effects of RBC age and leukoreduction on veterinary patient outcome are warranted. Implementation of evidence‐based transfusion guidelines and consideration of alternatives to allogenic blood transfusion are advisable.     

Blood transfusion in the perioperative period

In the perioperative period, blood transfusions are most commonly administered to address acute blood loss resulting from trauma, neoplasia, or surgery. In this setting, transfusions may be life saving, allowing time for clotting or surgical hemostasis. In recent years, however, there is a growing awareness that the administration of blood products may not be a benign treatment. In addition to the more commonly cited complications such as transfusion reactions, disease transmission, and electrolyte disturbances, blood transfusions have also been linked to poor surgical outcomes, increased risk of infection, cancer recurrence, and acute lung injury. The recognition of these problems has lead to more conservative transfusion strategies, and questioning of what constitutes an appropriate transfusion trigger. In this section, we will discuss the pathophysiology of acute blood loss, the benefits and risks of transfusions in surgical patients, management of perioperative blood transfusions, and alternative strategies to minimize the need for blood products.     

Autologous blood collection and transfusion in cats undergoing partial craniectomy

OBJECTIVE: To describe the procedure for autologous blood donation and associated complications in cats undergoing partial craniectomy for mass removal. DESIGN: Prospective case series. ANIMALS: 15 cats with intracranial mass confirmed by computed tomographic scan, no evidence of renal failure, and PCV > or = 22%. PROCEDURE: One unit (60 ml) of blood was collected and stored 7 to 17 days before surgery and transfused during the perioperative period if needed. The PCV was measured before donation, before surgery, during surgery, and after surgery to assess effect of donation on PCV before surgery and effect of transfusion on PCV after surgery. Cats were evaluated for donation complications, iatrogenic anemia, and adverse reactions associated with administration of autologous blood. RESULTS: Complications associated with phlebotomy were not detected. Fifteen cats underwent partial craniectomy 7 to 17 days after blood donation; all had histologic confirmation of meningioma by examination of tissue obtained at surgery. Eleven cats received autologous blood transfusions. None of the cats received allogeneic blood transfusions. Transfusion reactions were not observed. Subclinical iatrogenic anemia was detected in 3 cats. Two cats were considered to have received excessive transfusion, and 3 cats received inadequate transfusion. All cats undergoing partial craniectomy were discharged from the hospital and were alive > 6 months after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Autologous blood donation before surgery was considered safe for cats undergoing partial craniectomy for resection of meningioma. The only complication observed was iatrogenic anemia. The procedure contributed to blood conservation in our hospital.     

In vitro lysis and acute transfusion reactions with hemolysis caused by inappropriate storage of canine red blood cell products

Background: Transfusion of red blood cell (RBC) products carries considerable risk for adverse reactions, including life‐threatening hemolytic reactions. Objective: To report the occurrence and investigation of life‐threatening acute transfusion reactions with hemolysis in dogs likely related to inappropriate blood product storage. Animals: Four dogs with acute transfusion reactions and other recipients of blood products. Methods: Medical records were reviewed from 4 dogs with suspected acute hemolytic transfusion reactions after receiving RBC products at a veterinary clinic over a 1‐month period. Medical records of other animals receiving blood products in the same time period also were reviewed. Blood compatibility and product quality were assessed, subsequent transfusions were closely monitored, and products were diligently audited. Results: During or immediately after RBC product transfusion, 4 dogs developed hemolysis, hemoglobinuria, or both. Two dogs died and 1 was euthanized because of progressive clinical signs compatible with an acute hemolytic transfusion reaction. Blood type and blood compatibility were confirmed. RBC units from 2 blood banks were found to be hemolyzed after storage in the clinic's refrigerator; no bacterial contamination was identified. After obtaining a new refrigerator dedicated to blood product storage, the problem of hemolyzed units and acute transfusion reactions with hemolysis completely resolved. Conclusions: Acute life‐threatening transfusion reactions can be caused by inappropriate storage of RBC products. In addition to infectious disease screening and ensuring blood‐type compatibility, quality assessment of blood products, appropriate collection, processing, and storage techniques as well as recipient monitoring are critical to provide safe, effective transfusions.     

Results of blood transfusion in anemia of dairy cattle with references to serological tolerance

Therapeutic use of blood transfusion as a life-saving step in cases of dairy cattle anaemia cannot be recommended unless serological tolerance is taken into due consideration. The results obtainable from cross-testing and biological testing are useless in avoiding transfusion problems caused by blood groups in situations of first transfusion. Suitable donors can be identified only by haemolysis and haemolysis inhibition tests. Preliminary selection of donors in advance is permissible for first transfusions. The most important antigens, which may correspond with normal agglutinins, must not be present in the blood patterns of selected donors. Blood transfusion without knowledge of serological tolerance and compatibility between donor and recipient may be justified in emergency situations, yet, together with desensitisation.     

Principles of transfusion medicine in small animals.

The purpose of this review was to provide the reader with an updated overview of small animal transfusion medicine, and an approach to integrating it into private practice, based on a review of the veterinary and human literature spanning the last 3 decades. Electronic, online databases that were searched included CAB International and Medline; multiple keywords or subject headings were searched that were appropriate to each of the sections reviewed: canine and feline blood groups, blood-typing and crossmatching, donors, blood collection, storage, blood components, blood transfusion, blood component therapy, blood substitutes, and adverse reactions. The safe use of blood component therapy requires knowledge of blood groups and antibody prevalence, and knowledge of the means to minimize the risk of adverse reactions by including the use of proper donors and screening assays that facilitate detection of serological incompatibility. The 2 assays available to the practitioner are crossmatching, which is readily done in-house, and blood typing. Blood typing is available in the form of a commercial testing kit, through use of purchased reagents, or via a request to an external laboratory. The risk of potentially fatal adverse reactions is higher in cats than in dogs. The decision to transfuse and the type of product to administer depend on several factors, such as the type of anemia and the size of the animal. In conclusion, transfusion medicine has become more feasible in small animal practice, with improved access to blood products through either on-site donors, the purchase of blood bank products, external donor programs, or the availability of blood component substitutes.     

Feline transfusion practice in South Africa: current status and practical solutions

Blood transfusion therapy is often under-utilised in feline practice in South Africa. However, it is a technique that can be safely and effectively introduced in practice. Cats have naturally occurring allo-antibodies against the blood type that they lack, which makes blood typing, or alternatively cross-matching, essential before transfusions. Feline blood donors must be carefully selected, be disease free and should be sedated before blood collection. The preferred anticoagulant for feline blood collection is citrate-phosphate-dextrose-adenine. Blood can either be administered intravenously or into the medullary cavity, with the transfusion rate depending on the cat's hydration status and cardiac function. Transfusion reactions can be immediate or delayed and they are classified as immunological or non-immunological. Indications, methods and techniques to do feline blood transfusions in a safe and economical way are highlighted.     

Red blood cell transfusions in cats: 126 cases (1999)

OBJECTIVE: To determine the number of and reasons for RBC transfusions, incidence of acute transfusion reactions, prevalence of blood types, volume of blood administered, change in PCV, and clinical outcome in cats. DESIGN: Retrospective study. ANIMALS: 126 cats that received RBC transfusions. PROCEDURE: Medical records of cats that received whole blood or packed RBC transfusions were reviewed for signalment, blood type, pre- and post-transfusion PCV, volume of blood product administered, clinical diagnosis and cause of anemia, clinical signs of acute transfusion reactions, and clinical outcome. RESULTS: Mean volume of whole blood administered i.v. was 172 mL/kg (7.8 mL/lb) versus 9.3 mL/kg (4.2 mL/lb) for packed RBCs. Ninety-four percent of cats had blood type A. Mean increase in PCV among all cats was 6%. Fifty-two percent of cats had anemia attributed to blood loss, 10% had anemia attributed to hemolysis, and 38% had anemia attributed to erythropoietic failure. Acute transfusion reactions occurred in 11 cats. Sixty percent of cats survived until discharge. CONCLUSIONS AND CLINICAL RELEVANCE: RBC transfusions resulted in an increase in PCV in cats with all causes of anemia in this study. The rate of death was greater than in cats that did not receive transfusions, but seriousness of the underlying disease in the 2 groups may not be comparable. Death rate of cats that received transfusions was not attributable to a high rate of transfusion reactions. Results confirm that pretransfusion blood typing or crossmatching is required to minimize the risk of adverse reactions.     

Acute Hemolytic Transfusion Reaction in an Abyssinian Cat With Blood Type B

After receiving a transfusion with unmatched blood, an anemic Abyssinian cat developed an acute hemolytic transfusion reaction. Similar to many other purebred cats, the recipient had type B blood with strong serum anti-A alloantibodies, whereas the donor had blood type A. Subsequent transfusions with type B blood proved effective and without adverse reactions. This case of a clinical A-B incompatibility reaction emphasizes the need for blood typing and/or crossmatching prior to transfusing cats.     

Indications and Techniques for Blood Transfusion in Birds

There is growing medical care related to emergency presentations and procedures used to treat companion and wild birds. These critical care procedures (e.g., blood transfusion) can be life-saving. To maximize the beneficial effects of blood transfusions administered to avian patients, it is necessary to have an understanding of avian hematology and erythropoiesis, recognize clinical conditions in which one performs a blood transfusion, know the proper procedures and techniques, and rapidly identify possible adverse reactions.     

Transfusion issues in the cancer patient

Blood transfusions are a lifesaving but transient therapy used to correct deficiencies of blood cells and coagulation factors that occur in cancer patients. Anemia can occur in cancer patients as a result of hemolysis, blood loss, or bone marrow failure. The blood component most commonly recommended for the treatment of anemia is packed red blood cells. Coagulation disorders are common with hemangiosarcoma and diffuse hepatic tumors. Fresh frozen plasma is used as a source for replacement coagulation factors for the treatment of disseminated intravascular coagulation or other cancer-associated coagulopathies. Although thrombocytopenia and neutropenia can be the result of bone-marrow failure from tumor infiltration, chemotherapy, or radiation therapy, these platelets and neutrophils are rarely transfused to veterinary cancer patients. Pretransufsion testing consists of blood typing in cats, and cross matching in dogs and cats if the dog has previously been transfused. Cancer patients receiving transfusions should be monitored on a continual basis during and immediately following the transfusion to enable early identification of an adverse event, allowing the transfusion to be discontinued.     

Clinical and clinicopathologic variables in adult horses receiving blood transfusions: 31 cases (1999-2005)

OBJECTIVE: To determine clinical and clinicopathologic abnormalities in horses administered a blood transfusion and evaluate effects of blood transfusion on these variables. DESIGN: Retrospective case series. ANIMALS: 31 adult horses that received > or = 1 blood transfusion. Procedures-Medical records of horses receiving a blood transfusion were reviewed to obtain clinical findings, laboratory test results before and after transfusion, adjunctive treatments, transfusion type and volume, response to transfusion, results of donor-recipient compatibility testing, adverse reactions, and outcome. RESULTS: 31 horses received 44 transfusions for hemorrhagic anemia (HG; n = 18 horses), hemolytic anemia (HL; 8), or anemia attributable to erythropoietic failure (EF; 5). Tachycardia and tachypnea were detected in 31 of 31 (100%) and 22 of 31 (71%) horses, respectively, before transfusion. The PCV and hemoglobin concentration were less than the reference range in 11 of 18 horses with HG, 8 of 8 horses with HL, and 5 of 5 horses with EF. Hyperlactatemia was detected in 16 of 17 recorded values before transfusion. Heart rate, respiratory rate, and PCV improved after transfusion, with differences among the types of anemia. Seventeen (54%) horses were discharged, 9 (29%) were euthanized, and 5 (16%) died of natural causes. Adverse reactions were evident during 7 of 44 (16%) transfusions, varying from urticarial reactions to anaphylactic shock. CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities in clinical and clinicopathologic variables differed depending on the type of anemia. Colic, cold extremities, signs of depression, lethargy, tachycardia, tachypnea, low PCV, low hemoglobin concentration, and hyperlactatemia were commonly detected before transfusion and resolved after transfusion.     

Retrospective Study: Incidence of transfusion reactions to commercial equine plasma

Objective – To report on the incidence of transfusion reactions to commercial equine plasma in a hospital‐based population of horses, to characterize these reactions and report on outcome. Design – Retrospective study. Setting – University teaching hospital. Animals – Client‐owned horses referred to the University of Wisconsin. Interventions – Intravenous administration of 2 commercial equine plasma products when clinically indicated. Measurements and Main Results – Medical records of 107 horses that received plasma transfusions between 2003 and 2008 were evaluated. Transfusion reactions were recorded in 6 of 107 transfusions. All individuals were administered plasma from 1 commercial source. Foals <30 days of age received a hypergammaglobulinemic product and all adults received a lower IgG concentration product. No reactions were recorded in adults. In foals (<30 d) reactions were recorded in 6 of 69 cases (8.7%), all of which occurred in neonates <7 days of age (6/62; [9.7%]). The most frequent reactions were fever (4/6), tachycardia (2/6), tachypnea (2/6), and colic (2/6). All affected foals survived the reaction. There were no statistically significant differences (P<0.05) in any of the variables examined between those foals that did and those that did not experience transfusion reactions. Conclusion – The incidence of transfusion reactions was 8.7% in foals and 0% in adult horses in our referral population. Five of 6 foals responded to medical therapy and eventually received the clinically indicated transfusion. No transfusion related mortality occurred.     

Whole blood transfusions in 91 cats: a clinical evaluation

This survey assessed the feline transfusion practices at the University of Berlin from 1998 to 2001 in regard to patient population, indications, efficacy, and transfusion reactions. Blood was obtained from seven healthy in-house donors and 127 mostly indoor client-owned pet cats. Over a 3-year period 91 cats were transfused with blood type compatible blood. The blood was fresh (within 8 h of collection) or stored no longer than 15 days. Transfusions were required because of blood loss anaemia (n=40), haemolytic anaemia (n=13), ineffective erythropoiesis (n=35), hypoproteinaemia (n=2) or coagulopathy (n=2). The anaemic cats had a pretransfusion haematocrit of 5-20% (m [median]=13), and received one to six transfusions (m=1). The survival rates of the anaemic cats at 1 and 10 days after transfusion were 84 and 64%, respectively. None of the deaths appeared to be related to transfusion reactions. The major crossmatch, undertaken before 117 transfusions, was incompatible for eight cats. All except for one had previously been transfused. Lysis of transfused cells in six cases resulted in a less than expected haematocrit rise and an increase in serum bilirubin. Transient mild transfusion reactions were only noted in two cats during the second or third transfusion. In conclusion, with proper donor selection and appropriate compatibility screening, blood transfusions are well tolerated, appear effective, and may increase chances of survival.     

Canine and feline blood donor screening for infectious disease

Thousands of blood transfusions are performed each year on dogs and cats, and the demand for blood products continues to grow. Risks associated with transfusions include the risk of disease transmission. Appropriate screening of blood donors for bloodborne infectious disease agents should be performed to lessen this risk. Geographic restrictions of disease, breed predilection, and documentation of actual disease transmission by transfusion all are factors that might need to be considered when making a decision on what screening program to use. In addition, factors involving general health care and management of blood donors should be employed to further ensure blood safety.     

Platelet transfusion in thrombocytopenic horses

Platelet transfusions might be indicated in horses with thrombocytopenia. The need for a transfusion cannot be determined by platelet numbers alone, as primary or co‐existing disease processes, platelet function and age of the recipient also need to be considered. In patients with no co‐morbidities, relevant bleeding is uncommonly observed with platelet counts >10 x 10⁹/l and a therapeutic approach with initiation of treatment when signs of bleeding are observed might be justified.     

Blood transfusions as an immunomodulator--a review

Blood transfusions have been shown for two decades to prolong allograft survival. The mechanism is complex, involving both T lymphocytes and macrophages. In the last five years, transfusion induced immunosuppression has been shown to increase the rate of tumor growth and to increase susceptibility to infectious complications. Prevention of this immunosuppression may be possible by the concomitant use of immunomodulators which inhibit suppressor T lymphocyte function or block prostaglandin E production. A second potential but as yet unproven method is by use of frozen washed red blood cells when transfusions are required.     

Increasing patient safety in veterinary transfusion medicine: an overview of pretransfusion testing

Objectives – To review the principles and available technology for pretransfusion testing in veterinary medicine and discuss the indications and importance of test performance before RBC transfusion.
Data Sources – Current human and veterinary medical literature: original research articles and scientific reviews.
Summary – Indications for RBC transfusion in veterinary medicine include severe anemia or tissue hypoxia resulting from blood loss, decreased erythrocyte production, and hemolyzing conditions such as immune-mediated anemia and neonatal isoerythrolysis. Proper blood sample collection, handling, and identification are imperative for high-quality pretransfusion testing. Point-of-care blood typing methods including both typing cards and rapid gel agglutination are readily available for some species. Following blood typing, crossmatching is performed on one or more donor units of appropriate blood type. As an alternative to technically demanding tube crossmatching methods, a point-of-care gel agglutination method has recently become available for use in dogs and cats. Crossmatching reduces the risk of hemolytic transfusion reactions but does not completely eliminate the risk of other types of transfusion reactions in veterinary patients, and for this reason, all transfusion reactions should be appropriately documented and investigated.
Conclusion – The administration of blood products is a resource-intensive function of veterinary medicine and optimizing patient safety in transfusion medicine is multifaceted. Adverse reactions can be life threatening. Appropriate donor screening and collection combined with pretransfusion testing decreases the occurrence of incompatible transfusion reactions.     

Triggers for prophylactic use of platelet transfusions and optimal platelet dosing in thrombocytopenic dogs and cats.

Prophylactic platelet transfusions are frequently given to human patients with hypoproliferative thrombocytopenia. For several decades, the most common transfusion trigger was 20,000/microL, but the trend is now to use 10,000/microL in the absence of other risk factors for bleeding. This trigger seems to reduce the number of transfusions without increasing the risk of severe bleeding. Most studies involved in establishing platelet transfusion policies have involved patients with acute leukemia, with fewer studies involving patients undergoing hematopoietic stem cell transplantation or aggressive chemotherapy for other cancers and patients with aplastic anemia. In the presence of other risk factors for spontaneous bleeding, 20,000/microL is still considered an appropriate trigger. The trigger for prophylactic transfusion before surgery has not undergone the same recent scrutiny as has the trigger for spontaneous bleeding. The recommendation remains to raise the platelet count to 50,000 to 100,000/microL if possible, although it is recognized that surgery and other invasive procedures have been performed at lower platelet counts without major bleeding. Prophylactic transfusion is not used in disorders of platelet consumption and destruction to prevent spontaneous bleeding but is used before surgery. Because of the comparative lack of experience with platelet transfusion in veterinary medicine, it is difficult to make generalizations for dogs and cats. Using the guidelines established for therapeutic and prophylactic transfusion of human patients is a reasonable starting point, however. A therapeutic transfusion policy is suggested in the veterinary setting provided that the patient can be closely observed for critical bleeding and a prompt transfusion can be given. This policy should ultimately reduce the overall number of platelet transfusions given to hospital patients. If an animal cannot be closely observed or the ability to transfuse on demand is limited, prophylactic transfusion is recommended. The triggers for initiating a platelet transfusion in dogs are extrapolated from human data; these values are lower by 50% for cats. Because of the imprecision of platelet counting at low values, platelet counts must always be interpreted in conjunction with clinical signs of hemorrhage. If platelet-rich plasma or platelet concentrate is available, a dose of 1 platelet unit per 10 kg is recommended, although resources may dictate a smaller dose. This will raise the recipient platelet count by a maximum of about 40,000/microL. Assuming a trigger of 10,000/microL, a transfusion will probably be required approximately every 3 days. It must be remembered that the frequency of platelet transfusions may be greater in the presence of factors accelerating platelet loss or destruction. If fresh whole blood is used, a rule of thumb is to transfuse 10 mL/kg, which will raise the recipient platelet count by a maximum of approximately 10,000/microL. Daily transfusions or transfusions every other day will probably be required.     

Canine and feline blood transfusions: controversies and recent advances in administration practices

ObjectivesTo discuss and review blood transfusion practices in dogs and cats including collection and storage of blood and administration of products. To report new developments, controversial practices, less conventional blood product administration techniques and where applicable, describe the relevance to anaesthetists and anaesthesia.Databases usedPubMed and Google Scholar using dog, cat, blood transfusion, packed red blood cells and whole blood as keywords.ConclusionsBlood transfusions improve oxygen carrying capacity and the clinical signs of anaemia. However there are numerous potential risks and complications possible with transfusions, which may outweigh their benefits. Storage of blood products has improved considerably over time but whilst extended storage times may improve their availability, a phenomenon known as the storage lesion has been identified which affects erythrocyte viability and survival. Leukoreduction involves removing leukocytes and platelets thereby preventing their release of cytokines and bioactive compounds which also contribute to storage lesions and certain transfusion reactions. Newer transfusion techniques are being explored such as cell salvage in surgical patients and subsequent autologous transfusion. Xenotransfusions, using blood and blood products between different species, provide an alternative to conventional blood products.