1097CHAPTER 91 Transfusion Medicine dysfunction associated with transfusion (RDAT) was considered new if it appeared after the first RBC transfusion in the PICU A progressive RDAT was diagnosed if an[.]
CHAPTER 91 Transfusion Medicine dysfunction associated with transfusion (RDAT) was considered new if it appeared after the first RBC transfusion in the PICU A progressive RDAT was diagnosed if an RD was present before the transfusion and if the partial pressure of arterial oxygen/fraction of inspired oxygen (Pao2/Fio2) or peripheral capillary oxygen saturation/fraction of inspired oxygen (Spo2/Fio2) ratio dropped by at least 20% thereafter Among 136 transfused patients, 58 cases of RDAT (43% of transfused patients) were detected, including (7%) new RDAT and 49 (36%) progressive RDAT Higher severity of illness, MODS prior to transfusion, and volume (mL/kg) of RBC transfusion were independently associated with RDAT A dose-response relationship was observed between transfusion volume (milliliters per kilogram) and the incidence of RDAT Patients with RDAT developed more MODS, had a longer duration of intubation and PICU length of stay, and had higher mortality The conclusion was that RDAT is frequent in the PICU and occurs mainly in patients with prior RD, who would not be identified using current definitions for transfusion-associated respiratory complications RDAT is not recognized as a transfusion reaction by hemovigilance systems, but it seems to be a clinically significant transfusion complication RDAT should be studied further given the high incidence and serious adverse outcomes associated with it Transfusion-Associated Circulatory Overload. TACO is the leading cause of transfusion-related morbidity and mortality in North America.191 TACO is underreported to hemovigilance systems.202,205,206 From 2000 to 2009, 730 cases of TACO were reported to the Quebec Hemovigilance System.207 In 2013, 96 cases of TACO were collected by the British Haemovigilance Scheme; no TACO cases were reported in children.191 The AABB registered 834 cases of TACO in 2013 (1 in 13,144 transfusions of blood components).28 There are few data on the epidemiology of TACO in the PICU.133,187,197,204,208,209 The risk of contracting a TACO is likely higher in critically ill children because cardiac dysfunction, a wellrecognized risk factor for TACO, is common in the PICU.191,210 The diagnostic criteria of TACO are not well suited to critically ill children, which might explain why TACO is not reported to hemovigilance systems in this population.211 Two sets of diagnostic criteria of TACO are presently used: The 2018 ISBT-IHN-AABB definition of TACO is available at www.aabb.org/hemovigilance/domuments/TACO-2018-definition pdf Patients classified with TACO (surveillance diagnosis) should have acute or worsening respiratory compromise and/ or evidence of pulmonary edema (points and/or below) during or up to 12 hours after transfusion and presence of a total of or more of the following criteria: a Acute or worsening respiratory compromise (tachypnea, shortness of breath, cyanosis, and decreased oxygen saturation values in the absence of other specific causes; bronchospasm or wheezing can occur) b Evidence of acute or worsening pulmonary edema based on clinical physical examination (crackles on lung auscultation, orthopnea, cough, a third heart sound, and pinkish frothy sputum in severe cases), and/or radiographic chest imaging and/or other noninvasive assessment of cardiac function, such as echocardiogram (presence of new or worsening pleural effusions, widened vascular pedicle, progressive lobar vessel enlargement, peribronchial cuffing, bilateral Kerley lines, alveolar edema with nodular areas of increased opacity, and/or cardiac silhouette enlargement) c Evidence for cardiovascular system changes not explained by the patient’s underlying medical condition, including 1097 development of tachycardia, hypertension, widened pulse pressure, jugular venous distension, enlarged cardiac silhouette, and/or peripheral edema (hypotension may be a presenting feature) d Evidence of fluid overload including any of the following: a positive fluid balance; response to diuretic therapy or dialysis combined with clinical improvement; and change in the patient’s weight in the peritransfusion period (typically weight increase, but it can decrease following diuretic therapy) e Supportive result of a relevant biomarker, such as an increase of B-type natriuretic peptide level (e.g., BNP or NTpro BNP) above the age group-specific reference range and greater than 1.5 times the pretransfusion value A normal posttransfusion NP level is not consistent with a diagnosis of TACO TACO definition, according to the British Haemovigilance Scheme (Serious Hazards of Transfusion, SHOT) and the International Society of Blood Transfusion (ISBT)212: TACO is present if at least four of the five following criteria are met within hours of transfusion: (a) acute respiratory distress; (b) tachycardia; (c) increased blood pressure; (d) acute or worsening pulmonary edema; (e) evidence of positive fluid balance In 2009, no TACO was reported in a prospective cohort study of 136 consecutive PICU patients transfused with RBCs.213 A subsequent chart review was undertaken to ascertain whether TACO cases had been missed Attempts to use the criteria advocated by the British Haemovigilance Scheme211 were problematic because terms such as “tachycardia” and “increased blood pressure” were vaguely defined and did not provide age-adjusted reference ranges When using diagnostic criteria that compared heart rate or blood pressure with normal pediatric values or that assessed change between pre- and posttransfusion values, it was noted that the incidence rate of TACO could have ranged from 1.5% to 46% depending on the set of diagnostic criteria used TACO is probably frequent in the PICU The epidemiology of TACO can differ very significantly if different lists of diagnostic criteria of TACO are used or if diagnostic criteria unadjusted for children are used.211,214 Moreover, differentiating TACO and TRALI in critically ill patients can be very difficult, more so given that some patients can contract both TACO and TRALI.214 This implies that better diagnostic criteria of TACO must be developed for PICU patients TACO is most commonly associated with a rapid or massive transfusion that causes pulmonary edema secondary to heart failure Reduced cardiac reserve, chronic and severe anemia (Hb ,5 g/ dL), renal failure, positive fluid balance, and age (infants and elderly patients) are risk factors.215 The main symptoms are respiratory distress, hypoxemia, tachycardia, and hypertension When TACO is suspected, transfusion must be stopped and supportive treatment provided Slow transfusion (#1 mL/kg per hour) in at-risk patients can prevent TACO Hypotensive reactions are increasingly recognized, but their etiology remains uncertain.216 They are probably attributable to bradykinin generation, which can happen when a blood product is exposed to negatively charged surfaces (e.g., filters) The risk of hypotensive reaction is increased in patients receiving angiotensin-converting enzyme (ACE) inhibitors or with diminished bradykinin metabolism Hypotensive reactions are more frequently associated with platelets than with RBCs and plasma; however, we observed only five platelet-related hypotensive episodes among 3672 consecutive PICU admissions.217 Transfusion-related 1098 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology hypotension may happen alone or with some flushing; it occurs rapidly after transfusion begins Treatment is straightforward: the transfusion must be stopped and supportive treatment (i.e., fluid bolus) should be undertaken Other Acute Transfusion Reactions Nonhemolytic febrile reactions are the most frequent and benign acute transfusion reactions (1 in 300 RBC and in 20 platelet transfusions).218 In addition to fever, it can be accompanied by chills, discomfort, headache, and nausea or vomiting The symptoms usually occur toward the end or soon after a transfusion These reactions are mediated by pyrogenic substances that accumulate during storage or by the recipient’s antibodies that bind with leukocytes from the donated blood, which allow activation of the complement system and production of cytokines Acetaminophen can be used to minimize fever, but premedication with acetaminophen, diphenhydramine, or steroids is not useful A decrease in the incidence of these reactions is reported with prestorage leukocyte reduction.101,102 Acute hemolytic reactions may be much more serious They are caused by lysis or accelerated destruction of RBCs due to immunologic incompatibility between donor and recipient blood The mortality rate associated with transfusion errors is less than 10%.219 ABO mismatch is the most frequent and most severe of the blood group incompatibilities, with hemolysis and death as the results In most instances, mistransfusion is the cause, that is, the patient received an RBC unit that was prepared for another patient The risk that such errors happen is obviously higher in the context of emergency transfusion; its prevention warrants careful verification by medical staff of all blood products administered The reaction is characterized by fever, chills, discomfort, diffuse pain, and hemoglobinuria Hypotension, shock, renal failure, and DIC are also observed in some cases When such reactions are suspected, the transfusion must be stopped immediately and supportive treatment administered To avoid these hemolytic reactions, donor and recipient compatibility must be thoroughly checked (ABO and Rh types, unit identification number) and the recipient must be properly identified (name and medical record number) when the sample is taken for pretransfusion analyses as well as before the transfusion is started Many centers have instituted double verification by two different individuals for every assessment made Nonimmune hemolysis can be caused by mechanical trauma to RBCs, rapid administration through a small catheter, excessive warming or freezing, or contact with hypotonic solution Allergic transfusion reactions result from the interaction between donor allergens and recipient antibodies (IgE) that provoke a type I hypersensitivity reaction Other possible mechanisms include preexisting class-specific anti-IgA in patients with IgA deficiency, preexisting antibodies to polymorphic forms of other serum proteins (IgG, albumin, haptoglobin, and so on) that the patient is lacking, transfusion of allergens to which a patient is presensitized, (drugs, chemicals, and so on), and passive transfer of IgE antibodies to transfused patients.220 The reaction can be minor (e.g., isolated urticaria) or major (e.g., hypotension, anaphylactic shock, respiratory distress, digestive disorders) A severe reaction usually occurs quickly, whereas a benign reaction may occur up to hours after the transfusion is completed When an allergic reaction is suspected, the transfusion must be stopped and supportive treatment undertaken with antihistamines, steroids, and epinephrine if required Prevention must be considered Premedication of patients with antihista- mines is suggested if they have already presented two minor episodes In patients with major reactions, premedication with steroids and antihistamines can be used Washed RBC and platelet units can also be used Patients with anti-IgA antibodies must receive blood products from donors with IgA deficiency or products that have been washed several times Leukocyte reduction does not offer any benefit Bacterial contamination is more frequent with platelets than with RBC units or plasma since platelet concentrates are stored at 20°C to 24°C Contamination may be due to unsuspected bacteremia in the donor, skin flora when taking a blood sample from the donor, or issues related to product handling The most common microorganisms identified are Gram-negative bacteria, such as Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas species, and Gram-positive bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus The reaction is characterized by fever and chills and may lead to septic shock Symptoms usually appear during or within hours after transfusion When bacterial contamination is suspected, transfusion must be stopped immediately, wide spectrum antibiotics must be given (third-generation cephalosporin or b-lactam in combination with aminoglycoside) and supportive treatment administered The blood bank must be informed immediately, as other blood products from the same donor may need to be withdrawn Many descriptive studies have reported an association between RBC transfusion and necrotizing enterocolitis (NEC) in very-low-birth-weight neonates 221,222 The relevance of transfusion-related acute gut injury (TRAGI) in PICU patients is undetermined Delayed Transfusion Reactions Among the 321 adverse events reported in children by SHOT in the United Kingdom from 1996 to 2005,188 there were five cases of severe delayed transfusion reactions, including two cases of TAGVHD.115 TA-GVHD, which is rare but very serious, may occur when viable lymphocytes from a donor are infused into a recipient who is unable to reject them because of immunosuppression or partial HLA matching (closed donor genetic profile) Donor leukocytes can then persist in the recipient; since these lymphocytes recognize the recipient’s HLA antigens as foreign, an immune reaction is triggered Signs and symptoms (generalized skin rash, diarrhea, abnormal liver function or fever) appear to 10 days after transfusion.223 Associated complications are aplastic anemia with pancytopenia, which may lead to hemorrhage and severe infections The mortality rate is 90% The risk of TA-GVHD is higher in premature babies and if a patient with a congenital or acquired immunodeficiency receives a nonirradiated RBC unit or if the blood was a directed donation collected from a relative Neoplasia (e.g., leukemia, solid tumors), chemotherapy and transplantation (stem cell, bone marrow, solid organ),218 intrauterine transfusions, and exchange transfusions are other risk factors No effective treatment is recognized Prevention can be accomplished by irradiating blood products Delayed (extravascular) hemolytic reactions result from the interaction between recipient irregular alloantibodies and donor RBCs They involve either antibodies that were present prior to transfusion but were missed because they were undetectable by cross-matching or antibodies that appear after the transfusion Involved antibodies are usually E, Jka, c, Fya, and K.218 These reactions occur days to weeks after the transfusion Symptoms include anemia and jaundice The outcome is usually good except in some patients with sickle cell disease There is no specific treatment CHAPTER 91 Transfusion Medicine 1099 Posttransfusion purpura is characterized by dramatic, sudden, and self-limiting thrombocytopenia The pathogenesis is unclear but is presumably related to the development of platelet-specific antibody following transfusion The platelet count drops below 10,000/uL to 10 days after transfusion given in a patient with a history of sensitization by pregnancy or prior transfusion.224 Purpura and diffuse hemorrhages (mucosal, gastrointestinal, urinary, cerebral) may be observed The thrombocytopenia is refractory to platelet transfusion The mortality rate is 8% Treatment includes steroids, plasmapheresis, and immunoglobulins Complications Related to Massive Transfusion Massive transfusion is classically defined as the administration of more than one circulating volume of blood products within 24 hours, or more than 50% of the circulating blood volume in hours or less, or 10 RBC units in adults.225 This definition is not data driven and does not reflect when the risk of death occurs related to transfusion volume Data indicate that the risk of death increases after a child is transfused more than 40 mL/kg total of all blood products within 24 hours for active bleeding.226 As a result, this is a new data-driven definition of massive transfusion in children A number of complications may occur: (1) coagulopathy and dilutional thrombocytopenia, which may trigger bleeding; (2) hypothermia due to rapid infusion of cold blood products, which can lead to arrhythmias, platelet dysfunction, and cardiac dysfunction; (3) citrate toxicity that may trigger hypocalcemia, hypomagnesemia, and metabolic alkalosis; and (4) hyperkalemia.218 These complications can be avoided by various measures, including using a blood warmer if the transfusion rate exceeds 50 mL/kg per hour, close monitoring of the coagulation profile, platelet transfusion to maintain a count greater than 50,000/uL, plasma administration to control coagulopathy, cryoprecipitate administration to attain a fibrinogen level over 0.1 g/ dL, and monitoring of hypocalcemia and calcium supplementation, as required The use of whole blood instead of blood components can also reduce the risks associated with dilutional coagulopathy and citrate toxicity.227 Transfusion-Transmitted Infections In the United States, blood donation is tested at least for the following infectious agents: hepatitis A, B, and C; human immunodeficiency virus (HIV); human T-cell lymphotropic virus (HTLV); West Nile virus (seasonal); and syphilis.108 These tests and better donor selection have led to a significant decrease in the risk of transfusion-transmitted infectious diseases However, there will always be some residual risk, attributable to the window period (time from the beginning of an infection to the time when tests can detect the infection) and to false-negative results New emerging pathogens can also be a problem.228 Table 91.4 lists the risks of contracting specific infections with transfusion Transfusion-Related Immunomodulation There is strong evidence that transfusions might generate and/or enhance both anti- and proinflammatory reactions Clinically important immunosuppression is described in recipients of RBC units This immunosuppression is probably attributable to antiinflammatory substances (cytokines, lipids, free heme, and so on) in the supernatant of RBC units.2,229,230 It might explain the increased rates of nosocomial infections reported in transfused critically ill patients.132,231,232 On the other hand, many proinflammatory molecules are found in plasma-rich blood products, which may initiate, maintain, or enhance an inflammatory process The WBCs and these substances may trigger or maintain a systemic inflammatory response syndrome (SIRS) in transfusion recipients Administering transfusion to a critically ill patient with a SIRS may stimulate an inflammatory syndrome and constitute a “second hit,” which can cause additional organ dysfunction and contribute to MODS233 and perhaps ultimately result in higher mortality.234–238 Some clinical data suggest that these risks decrease significantly if the blood product is leukocyte reduced prior to storage.101,102,239 However, in vitro data suggest that some inflammatory mediators are active even in leukocyte-reduced RBC units.240 There are presently no data on this issue in pediatrics The clinical impact of transfusion on the immunologic responses of critically ill children remains to be determined Other Transfusion-Related Complications Other complications are associated with transfusion of blood products, including delirium241 and thromboembolism.242 The cause-effect relationship between these complications and transfusion remains to be determined Reactions and Complications More Frequent With Plasma Transfusion Overall, the noninfectious and infectious complications associated with FP are similar to those of RBC transfusions, excluding hemolysis The most notable risk associated with FP transfusion is TRALI There are antibodies and other biologically active substances in plasma, but hemovigilance data suggest that SD plasma and male-predominant plasma transfusion strategy are associated with a reduced incidence of TRALI.243 FP is known to have immunomodulatory properties,244 which may explain why plasma is associated with an increased risk of TRIM-related complications Epidemiologic studies have shown that adults and children transfused with plasma are more prone to contracting nosocomial infections.133 Additionally, large volumes of transfused FP can result in TACO Allergic reactions are also relatively common with FP transfusions (1%–3%) The risk of transfusion-transmitted viral infections is the same for FP and RBC units SD plasma has a reduced risk of infection related to enveloped viral pathogens, but the risk for nonenveloped viruses is not affected Thus, the risk could be higher with regard to emerging nonenveloped viruses Reactions and Complications More Frequent with Platelet Transfusion Major allergic reactions and bacterial contamination are the most frequent severe complications associated with platelet transfusion.245 Serious noninfectious complications of platelet transfusion are similar to those reported with plasma and RBCs with the exception of hemolytic transfusion reactions Rarely, hemolytic transfusion reactions can be seen after the transfusion of nonABO identical platelets, which contain anti-A or anti-B antibodies Platelet transfusion may also be associated with specific adverse effects, including platelet refractoriness due to HLA alloimmunization Prestorage leukocyte-reduced platelet products are available in most North American blood banks, which 1100 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology significantly decrease the risk of HLA alloimmunization and platelet refractoriness, nonhemolytic febrile reactions, and CMV transmission The most important infectious complication associated with platelet transfusion is bacterial infection As platelet concentrates are stored at room temperature, the incidence of bacterially contaminated platelet products is higher than with RBCs The risk of bacterial infection can be significantly reduced, but not eliminated, by bacterial testing (e.g., routine culture) Pathogens can also be inactivated by different methods using ultraviolet light.159 The risk of other transfusion-transmitted infections is similar for platelets and other blood components Treatment of Transfusion Reactions and Complications Patients should be monitored closely while receiving a transfusion Vital signs should be taken before transfusion as well as within the first 15 minutes and every hour up to to hours after transfusion The following symptoms and signs suggest that an acute blood reaction is occurring: fever, shivering (rigors), pain, anxiety, agitation, dyspnea, hypotension, hypertension, hemorrhage, shock, and hemoglobinuria (pink or red urine) If a transfusion reaction is suspected, the transfusion must be stopped immediately; an infusion of clear fluids must be maintained; all measures to ensure patient stability must be undertaken; verification that the patient received the correct unit must be ascertained; a visual inspection of the unit must be conducted and described in the patient hospital chart; clinical data related to the event must be detailed in the hospital chart; and the patient should be monitored for at least a few hours In many centers, the unit that was being transfused, the filter and tubing used, and the remaining blood product are returned to the blood bank A workup must be undertaken to assess for infection as well as to measure antibodies, antigens, free Hb, and sometimes other markers of metabolic disturbance (acidosis, hyperkalemia, hypocalcemia, and so on) All possible transfusion reactions must be reported to the appropriate blood agency or hemovigilance system, which is the blood bank in many hospitals Conclusion Transfusion of any blood product has had powerful connotations throughout history and across cultures and carries strong symbolic resonance, which can deeply affect the perspective of the transfusion recipient.246 A transfusion is indeed a serious matter not only for the patient and family but also for blood providers and the health system: it should be prescribed only if deemed necessary Close monitoring of the recipient is mandatory while a transfusion is given A transfusion can save a life but can also cause significant problems The risk of death attributable to transfusion of a labile blood product is low: only death over 2,845,459 blood component units was reported in the United Kingdom in 2008.247 However, serious reactions and severe complications can develop RBC, plasma, and platelet transfusions should be administered only if the anticipated benefits outweigh the potential risks A high proportion of transfusions are of unproven clinical benefit.40,248,249 Patient blood management programs exist in 37.7% of AABB-related hospitals and should be applied in all PICU patients.28 It is imperative to spread the concept of patient blood management and to generate new knowledge that will lead to better transfusion practices in the PICU (the right dose for the right patient for the right reasons at the right time).55,250 There are currently large gaps in knowledge; further studies are required to achieve this goal.11,40 Key References Bolton-Maggs PHB, on behalf of the SHOT Steering Group The 2015 Annual SHOT Report 2016:190 Cholette JM, Swartz MF, Rubenstein J, et al Outcomes using a conservative versus liberal red blood cell transfusion strategy in infants requiring cardiac operation Ann Thorac Surg 2017;103:206-214 Demaret P, Tucci T, Karam O, et al Clinical outcomes associated with red blood cell transfusions in critically ill children: a one-year prospective study Pediatr Crit Care Med 2015;16:505-514 Du Pont-Thibodeau G, Harrington K, Lacroix J Anemia and red blood cell transfusion in critically ill cardiac patients Ann Intensive Care 2014;4:16 Karam O, Lacroix J, Robitaille N, et al Association between plasma transfusions and clinical outcome in critically ill children: a prospective observational study Vox Sang 2013;104:342-349 Lacroix J, Hébert PC, Hutchison JS, et al., on behalf of the TRIPICU investigators, for the Canadian Critical Care Trials Group and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Transfusion strategies for patients in pediatric intensive care units N Engl J Med 2007;356:1609-1619 Oakley FD, Woods M, Arnold S, Young PP Transfusion reactions in pediatric compared with adult patients: a look at rate, reaction type, and associated products Transfusion 2015;55:563-570 Spinella PC, Cap AP Whole blood: back to the future Curr Opin Hematol 2016;23:536-542 Spinella PC, Tucci M, Fergusson DA, et al, for the ABC-PICU investigators, the Canadian Critical Care Trials Group, the PALISI Network, the BloodNet Pediatric Critical Care Blood Research Network, and the Groupe Francophone de Réanimation et Urgences Pédiatriques The age of transfused blood in critically ill children JAMA 2019;322:2179–2190 Valentine SL, Bateman ST, Bembea MM, et al., on behalf of the Pediatric Critical Care Transfusion and Anemia Expertise Initiative, the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute lung Injury and Sepsis Investigators (PALISI) Network: Consensus recommendations for red blood cell transfusion practice in critically ill children from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) Pediatr Crit Care Med 2018;19:884-898 The full reference list for this chapter is available at ExpertConsult.com e1 References Bateman ST, Lacroix J, Boven K, et al Anemia, blood loss and blood transfusion in North American children in the intensive care unit Am J Respir Crit Care Med 2008;178:26-33 Muszynski JA, Cholette JM, Acker JP, et al Transfusion-Related Immunomodulation in the Pediatric Intensive Care Unit Transfusion 2017;57:195-206 Bolton-Maggs PHB, on behalf of the SHOT Steering Group The 2015 Annual SHOT Report London: Serious Hazards of Transfusion; 2016 Lacroix J, Hébert PC, Hutchison JH, et al Transfusion strategies for patients in pediatric intensive care units N Engl J Med 2007; 356:1609-1619 Tucci M, Willems A, Toledano BJ, et al Association between length of red blood cell (RBC) storage and multiple organ dysfunction syndrome (MODS) in pediatric intensive care Crit Care Med 2007;334:A72 Watson GA, Sperry JL, Rosengart MR, et al Fresh frozen plasma is independently associated with a higher risk of multiple organ 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Crit Care Med 2005;33:1662-1663 16 Doctor A, Platt R, Sheram ML, et al Hemoglobin conformation couples erythrocyte S-nitrosothiol content to O2 gradients Proc Natl Acad Sci U S A 2005;102:5709-5714 17 Spinella PC, Tucci M, Fergusson DA, et al The age of transfused blood in critically ill children JAMA 2019;322:2179– 2190 18 Bennett-Guerrero E, Veldman TH, Doctor A, et al Evolution of adverse changes in stored RBCs Proc Natl Acad Sci U S A 2007; 104:17063-17068 19 Kim-Shapiro DB, Lee J, Gladwin MT Storage lesion: Role of red blood cell breakdown Transfusion 2011;51:844-851 20 Rubin O, Canellini G, Delobel J, Lion N, Tissot JD Red blood cell microparticles: clinical relevance Transfus Med Hemother 2012; 39:342-347 21 Carson JL, Noveck H, Berlin JA, Gould SA Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion Transfusion 2002;42:812-818 22 Shander A, Javidroozi M, Naqvi S, et al An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME) Transfusion 2014;54:26882695 23 Carson JL, Patel MS Red blood cell transfusion thresholds: can we go even lower? Transfusion 2014;54:2593-2594 24 Lackritz EM, Campbell CC, Ruebush TK, et al Effect of blood transfusion on survival among children in a Kenyan hospital Lancet 1992;340:524-528 25 Lackritz EM, Hightower AW, Zucker JR, et al Longitudinal evaluation of severely anemic children in Kenya: The effect of transfusion on mortality and hematologic recovery AIDS 1997;11:1487-1494 26 English M, Ahmed M, Ngando C, Berkley J, Ross A Blood transfusion for severe anaemia in children in a Kenyan hospital Lancet 2002;359:494-495 27 Goel R, Chappidi MR, Patel EU, et al Trends in red blood cell, plasma, and platelet transfusions in the United States, 1993-2014 JAMA 2018;319:825-827 28 Rajbhandary S, Whitaker BI, Perez GE The 2014-15 AABB Blood Collection, Utilization, and Patient Blood Management Survey Report AABB; 2018 29 Demaret P, Tucci T, Ducruet T, Trottier H, Lacroix J Red blood cell transfusion in critically ill children Transfusion 2014;54:365-375 30 Fitch K, Bernstein SJ, Aguilar MD, et al The RAND/UCLA Appropriateness Method User’s Manual Santa Monica: Rand; 2001 31 Bembea MM, Cheifetz IM, Fortenberry JD, et al Recommendations for red blood cell transfusions for the critically ill child receiving support from extracorporeal membrane oxygenation, ventricular assist and renal replacement therapy device from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) Pediatr Crit Care Med 2018;19(suppl 9):S157-S162 32 Bembea MM, Valentine SL, Bateman ST, et al The pediatric critical care transfusion and anemia expertise initiative consensus conference methodology Pediatr Crit Care Med 2018;19(suppl 9):S93-S97 33 Cholette JM, Willems A, Schwartz S, on behalf of the Pediatric Critical Care Transfusion and Anemia Expertise Initiative, the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Recommendations on red blood cell transfusions in infants and children with acquired and congenital heart disease from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) Pediatr Crit Care Med 2018;19(suppl 9):S137-S148 34 Demaret P, Emeriaud G, Hassan NE, et al Recommendations for red blood cell transfusions in critically ill children with acute respiratory failure from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) Pediatr Crit Care Med 2018;19(suppl 9):S114-S120 35 Karam O, Russell RT, Stricker P, et al Recommendations on red blood cell transfusions in critically ill children with non-life threatening or life-threatening bleeding from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) Pediatr Crit Care Med 2018;19(suppl 9):S127-S132 36 Muszynski JA, Guzetta N, Hall MW, et al Recommendations on red blood cell transfusion for critically ill children with non-hemorrhagic shock from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) Pediatr Crit Care Med 2018;19(suppl 9):S121-S126 37 Steffen KM, Bateman ST, Valentine SL, et al Implementation of the pediatric critical care transfusion and anemia expertise initiative (TAXI) red blood cell transfusion clinical recommendations Pediatr Crit Care Med 2018;19(suppl 9):S170-S176 38 Steiner ME, Zantek ND, Stanworth SJ, et al Recommendations on red blood cell transfusion support in children with hematologic and oncologic diagnoses: recommendations from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) Pediatr Crit Care Med 2018;19(suppl 9):S149-S156 39 Tasker RC, Turgeon AF, Spinella PC, on behalf of the Pediatric Critical Care Transfusion and Anemia Expertise Initiative, the Pediatric ... appear during or within hours after transfusion When bacterial contamination is suspected, transfusion must be stopped immediately, wide spectrum antibiotics must be given (third-generation cephalosporin... circulating volume of blood products within 24 hours, or more than 50% of the circulating blood volume in hours or less, or 10 RBC units in adults.225 This definition is not data driven and does... a child is transfused more than 40 mL/kg total of all blood products within 24 hours for active bleeding.226 As a result, this is a new data-driven definition of massive transfusion in children