e7 249 Stanworth SJ, Grant Casey J, Lowe D, et al The use of fresh frozen plasma in England high levels of inappropriate use in adults and children Transfusion 2011;51 62 70 250 Waters JH, Yazer MH Pa[.]
e7 249 Stanworth SJ, Grant-Casey J, Lowe D, et al The use of fresh-frozen plasma in England: high levels of inappropriate use in adults and children Transfusion 2011;51:62-70 250 Waters JH, Yazer MH Patient blood management: where’s the bottom? Transfusion 2015;55:700-702 251 MacDonald N, Scott JW, McCombie N, Robillard P, Giulivi A Transfusion risk of infection in Canada: Update 2006 Can J Infect Dis Med Microbiol 2006;17:103-105 252 MacDonald NE, O’Brien SF, Delage G, Canadian Paediatric Society, Infectious Diseases and Immunization Committee Transfusion and risk of infection in Canada: Update 2012 Paediatr Child Health 2012;17:e102-e111 253 Kamram M, Rachoin JS, Schort CA, Patel R, Parrillo JE, Gerber DR Risk of cardiac arrhythmias and conduction abnormalities in patients with severe sepsis and septic shock receiving packed red blood cell transfusions Crit Care Med 2008;36:A155 254 Elder AF Transfusion reactions In: Hillyer CD, Strauss RG, Luban NLC, eds Handbook of pediatric transfusion medicine San Diego: Elsevier Academic Press; 2004 255 Singer R, Giulivi A, Bodie-Collins M, et al Transfusion-related malaria in Canada Can Med Assoc J 2001;164:377-379 256 Kain KC, Bu Jassoum S, Fong W, Hannach B Transfusiontransmitted babesiosis in Ontario: First reported case in Canada Can Med Assoc J 2001;164:1721-1723 257 Rolain JM, Foucault C, Guieu R, La Scola B, Brouqui P, Raoult D Bartonella quintana in human erythrocytes Lancet 2002;360:226228 258 Urwin PJ, Mackenzie JM, Llewelyn CA, Will RG, Hewitt PE Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study Vox Sang 2016;10:310-316 e8 Abstract: The transfusion of red blood cells (RBCs), plasma, and/ or platelets can be lifesaving However, a transfusion should be prescribed only if deemed necessary because it can cause serious transfusion-related complications Previously published guidelines can help practitioners recognize when an RBC transfusion should be given or considered in critically ill children RBC transfusion is mandatory in hemorrhagic shock or if the hemoglobin concentration is less than g/dL Plasma and platelets can be useful when severe bleeding is attributable to coagulopathy, but there is no evidence that they can prevent bleeding Key words: Red blood cell, plasma, platelets, bleeding transfusion reaction 92 Hematology and Oncology Problems JESSE WENGER, CORINNE SUMMERS, AND JOAN S ROBERTS PEARLS • Proactive treatment measures for tumor lysis syndrome include hydration with hypotonic or isotonic saline solution; alkalinization; use of allopurinol or urate oxidase; avoidance of exogenous potassium; close monitoring of fluid status; and frequent monitoring of serum potassium, sodium, chloride, bicarbonate, calcium, phosphorus, uric acid, blood urea nitrogen, and creatinine concentrations • Clinically significant hyperleukocytosis occurs with a white blood cell count greater than 200,000/µL in acute myeloid leukemia and greater than 300,000/µL in acute lymphocytic leukemia • Concurrent thrombocytopenia and hyperleukocytosis increase risk of adverse outcomes, including intracranial hemorrhage and death Aggressive therapy to correct coagulopathy with fresh frozen plasma and vitamin K and to maintain platelet count higher than 20,000/µL is critical Hematologic Emergencies Anemia Anemia results from a deficiency in the oxygen-carrying capacity of the blood The deficit may be in the number of red blood cells (RBCs), the RBC hemoglobin (Hb) concentration, or both Because Hb serves as the primary transport molecule for oxygen (O2), anemia may affect the delivery of O2 to the tissues, with wide-ranging potential complications Under steady-state conditions, O2 consumption remains constant and is independent of O2 delivery until it falls below a critical level, which varies for each organ system When the Hb concentration decreases to approximately g/dL or less, O2 delivery and consumption may be compromised Below this level, O2 consumption becomes delivery dependent The body responds to acute, normovolemic anemia by increasing cardiac output through increases in stroke volume, heart rate, or both As the hematocrit falls, blood viscosity diminishes, increasing venous return and augmenting preload In the patient with chronic anemia, increases in cardiac output are supplemented by increased levels of 2,3-diphosphoglycerate shifting the oxyhemoglobin curve to the right and augmenting O2 delivery at the tissue level Anemias generally are classified either by the mechanism resulting in the Hb deficit—decreased production, accelerated destruction, or loss of erythrocytes—or by the • Childhood mediastinal masses produce few symptoms until they have occluded a substantial portion of the cross-sectional area of the trachea or mainstem bronchi or the superior vena cava Diagnosis should be established with the least invasive means available because these patients are at significant risk for anesthetic complications • Spinal cord compression most frequently occurs as metastatic disease and requires emergent treatment with mg/kg of dexamethasone over 30 minutes, as well as neurosurgical consultation • Hemophagocytic lymphohistiocytosis produces severe illnesses that may be confused with other forms of systemic inflammatory response syndrome, such as sepsis Appropriate diagnosis is tantamount; if the condition is left untreated, it is almost always fatal morphologic appearance of the erythrocyte, including size, Hb concentrations, and shape variation (Table 92.1).1 The normal values for mean corpuscular volume and mean corpuscular Hb concentration vary with the child’s age A wide variety of conditions, some intrinsic to the erythrocyte and others related to extrinsic factors, may result in abnormal RBC morphology The more common causes of profound anemia encountered in the pediatric intensive care setting are reviewed here Regardless of cause, transfusion of pediatric critical care patients has received intensive investigation, and recommendations for transfusion have emerged balancing the benefit of increased RBC O2-carrying capacity with potential risks Current recommendations for packed red blood cell (PRBC) transfusion to subgroups of pediatric patients share a goal of reducing the frequency and volume of PRBC transfusions; in most cases, transfusion is indicated for Hb g/dL or less and not indicated for Hb g/dL or greater, with use of clinical judgment for values between these thresholds (see also Chapter 91).2 Hemorrhagic Anemia Bleeding may be either acute and normocytic or chronic, which becomes microcytic due to depletion of iron stores In response, physiologic mechanisms to increase O2 delivery and tolerate Hb 1101 1102 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology TABLE Mechanisms of Anemia 92.1 Mechanism and Examples Changes in Laboratory Data Loss or Destruction Bleeding h Reticulocyte count Autoimmune hemolytic anemia h Reticulocyte count Hereditary spherocytosis h LDH Sickle cell anemia h Indirect bilirubin g Haptoglobin Poor Production Anemia of chronic inflammation Normal or g MCV g Reticulocyte count Pure red cell aplasia h MCV g Reticulocyte count Aplastic anemia h MCV g Reticulocyte count gh Neutropenia hg Thrombocytopenia Nutritional Deficiency Iron deficiency h MCV g Reticulocyte count g Ferritin g Iron saturation h TIBC Folate deficiency h MCV Vitamin B12 deficiency g Reticulocyte count LDH, Lactate dehydrogenase; MCV, mean corpuscular volume; TIBC, total iron binding capacity levels well below the normal range include tachycardia, increased stroke volume, and augmented contractility Signs of significant cardiovascular compromise may not become evident until the child has lost at least 25% of total blood volume, when patients usually manifest age-appropriate systolic hypotension.3 Signs and symptoms of acute hemorrhage result from poor endorgan perfusion, with consequent diminished O2 delivery However, signs of impending shock—such as pallor, anxiety, and tachypnea—may be subtle Initial management should include achieving hemostasis, establishing a secure airway, maintaining ventilation, and initiating volume replacement via an adequate intravenous catheter RBC transfusion should be given if O2 delivery to the end organs is inadequate Either whole blood or PRBCs can be used, but the former has many difficulties related to storage and transport (see also Chapter 91) If PRBCs or plasma-poor red cells are used to correct O2-carrying capacity during massive blood loss, deficits of coagulation factors develop earlier than during transfusion of whole blood Hypofibrinogenemia generally develops first, followed by deficits in other clotting factors and later by thrombocytopenia Fresh frozen plasma, platelets, and cryoprecipitate should be used to treat coagulopathy that develops during replacement of massive blood loss with PRBCs Other clinical abnormalities associated with replacement of large volumes of RBCs include hyperkalemia, hypocalcemia, and transfusion reactions Transfusion of platelets should be guided by serial platelet counts Central venous pressure should be monitored to allow for rapid administration of RBCs and volume replacement while decreasing the risks of hypervolemia Blood and other fluids may be administered rapidly until central venous pressure rises to to mm Hg Anemia Secondary to Decreased Production Screening laboratory tests are invaluable in distinguishing the types of anemia associated with diminished blood cell production: reticulocyte count, red cell size, and evaluation of other cell lines in addition to a careful history direct further evaluation Nutritional deficiencies typically involve either microcytic (iron) or macrocytic (B12, folate) isolated RBC anemia Anemia of chronic disease, microcytic or normocytic, is extremely common and is the end product of several processes Inflammation increases expression of hepcidin, a key regulator of iron metabolism, and interleukin-6 (IL-6), a proinflammatory cytokine Through its effect on ferroportin, hepcidin activity leads to decreased gastrointestinal iron absorption and increased iron sequestration in macrophages, reducing its availability for erythropoiesis IL-6 promotes iron sequestration by upregulation of hepcidin via the JAK/Stat pathway Other proinflammatory cytokines—such as IL-1, tumor necrosis factor-a, and interferon-g, seem to inhibit erythropoiesis by impairing erythropoietin sensitivity and erythroid lineage differentiation.1 Currently, the most effective intervention for anemia of chronic inflammation is to treat the underlying disease Anemia associated with thrombocytopenia represents a broad array of clinical entities (Box 92.1), most commonly acquired aplastic anemia, defined by at least two of the three following factors: granulocytes less than 500/µL, platelets less than 20,000/µL, and anemia with a corrected reticulocyte count less than 1% in conjunction with markedly hypocellular bone marrow.4 The majority of cases have no definable cause but the pathophysiology appears immune mediated, with destruction of blood-forming cells by lymphocytes Irrespective of the etiology of bone marrow failure, life-threatening complications may arise from blood cytopenias The most common causes of death are bacterial sepsis and fungal infection secondary to refractory granulocytopenia Broadspectrum antibiotics should be used to treat suspected infection in the granulocytopenic patient Historically, Gram-negative • BOX 92.1 Classification of Aplastic Anemia A. Isolated Anemia 3 4 5 6 Anemia of chronic inflammation Congenital sideroblastic anemia Transient erythroblastopenia of childhood Paraneoplastic Autoimmune Infections B. Complex Anemia 3 4 5 Diamond-Blackfan anemia Fanconi anemia Dyskeratosis congenital Shwachman-Diamond syndrome Acquired aplastic anemia CHAPTER 92 Hematology and Oncology Problems organisms were the most frequent cause of fulminant infection in this patient population With the increased use of central venous catheters, Gram-positive organisms now predominate.5 Antifungal therapy should be instituted in patients who fail to defervesce within to days of treatment with antibiotics Platelet transfusions should be used judiciously in an effort to avoid alloimmunization to platelet antigens and are generally reserved for episodes of active bleeding Similarly, RBC transfusions should be reserved for patients whose O2 delivery may be compromised as a result of profound anemia The patient should not receive blood products donated by family members to avoid sensitization to leukocyte and platelet antigens of potential bone marrow donors All blood products should be irradiated and leukodepleted to decrease the risk of graft-versus-host disease, with preference given to single-donor apheresis units Treatment of severe acquired aplastic anemia involves either the use of immunosuppressive therapy or replacement of bone marrow through stem cell transplantation The treatment of choice, bone marrow or peripheral blood stem cell transplantation from a histocompatible sibling, produces long-term survival rates of 75% to 80%.6 Unfortunately, up to 70% of patients may lack a suitably matched sibling donor Stem cells harvested from a matched unrelated donor, or umbilical cord blood, produce poorer outcomes because of the higher rate of graft-versus-host disease For these patients, immunomodulation, which usually includes a combination of antithymocyte globulin and cyclosporin, often with use of hematopoietic growth factors, has resulted in response rates of 70% to 80%.7 Hemolytic Anemia Hemolysis, the destruction of RBCs with liberation of Hb, may occur within either the blood vessels (intravascular hemolysis) or the reticuloendothelial system (extravascular hemolysis) Anemia results when the rate of RBC destruction exceeds new RBC production in the bone marrow Laboratory findings in patients with hemolytic anemia usually include increased reticulocyte count and elevated serum concentrations of unconjugated bilirubin and lactate dehydrogenase Intravascular hemolysis usually results in decreased serum haptoglobin concentrations Premature destruction of RBCs may result from intrinsic RBC abnormalities, such as hemoglobinopathies from red cell membrane defects or from a variety of extrinsic factors (see Table 92.1).1 Numerous Hb variants resulting in shortened RBC survival have been identified Individuals with sickling hemoglobinopathies may suffer a variety of complications that require treatment in an ICU (see Chapter 89) Abnormalities in the structure of the RBC membrane, as in hereditary spherocytosis, or decreased quantities of RBC enzymes, as in glucose-6-phosphate dehydrogenase (G6PD) deficiency, also decrease red cell survival Hemolysis in these settings occurs primarily extravascularly Mechanical disruption of the red cell membrane secondary to factors extrinsic to the RBC may lead to macroangiopathic hemolytic anemia, as with turbulent flow around a prosthetic heart valve, or microangiopathic hemolytic anemia, caused by fibrin deposition in the microvasculature The latter process is seen in consumptive disorders, including disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), and thrombotic thrombocytopenic purpura (TTP).8 In these entities, hemolysis is primarily intravascular, with characteristic schistocytes seen on the blood smear The hemolytic processes that result from abnormal interactions between erythrocytes and the immune system are known 1103 • BOX 92.2 Classification of Autoimmune Hemolytic Anemia (AIHA) in Children A. Primary AIHA Warm-reactive autoantibodies, usually IgG Paroxysmal cold hemoglobinuria, usually IgG Cold agglutinin disease, usually IgM B. Secondary AIHA 3 4 5 Systemic autoimmune disease (e.g., lupus) Malignancy (Hodgkin and non-Hodgkin lymphoma) Immunodeficiency Infection (Mycoplasma, viruses) Drug induced IgG, Immunoglobulin G; IgM, immunoglobulin M collectively as autoimmune hemolytic anemia (AIHA) AIHA can be classified as either primary, in which there is no identifiable systemic illness except possibly a history of a recent viral-like illness, or secondary, in which the hemolytic anemia is present in the context of another illness AIHA has been reported as a manifestation of autoimmune disorders (e.g., lupus erythematosus), immunodeficiency disorders, malignancies, specific infections, or as a drug reaction (Box 92.2).8 AIHA also may be classified by the thermal sensitivity of the autoantibodies The most common form is the result of warm-reactive immunoglobulin G (IgG) autoantibodies directed against RBC membrane proteins Extravascular hemolysis occurs, with sensitized erythrocytes cleared primarily in the spleen Cold-agglutinin disease, the second most common form of AIHA, most frequently occurs with Mycoplasma pneumoniae infections, but it also is associated with other infectious agents, including Epstein-Barr virus, cytomegalovirus, and mumps virus In this disorder, IgM autoantibody binds to the RBC and fixes complement The erythrocytes may undergo intravascular hemolysis, or they may be cleared by the reticuloendothelial system, primarily in the liver Paroxysmal cold hemoglobinuria is a rare variant of AIHA that usually occurs following a viral illness and in which an IgG autoantibody binds at cold temperature to the P-antigen of the erythrocyte, fixing complement (the DonathLandsteiner antibody) and producing intravascular hemolysis Although drug-induced autoantibodies occur uncommonly in children, they may follow exposure to some antibiotics, including penicillins and cephalosporins Mechanisms of drug-induced hemolysis may include autoantibody formation and adsorption of the drug onto the red cell membrane, with immune complex formation with IgG or IgM Patients with AIHA usually present with pallor, jaundice, and splenomegaly on physical examination The reticulocyte count is generally elevated, although initially it may be low or normal The direct antiglobulin test (Coombs test) demonstrates the presence of antibodies or complement on the red cells The indirect antiglobulin test measures the presence of unbound antierythrocyte antibodies in the patient’s serum Therapy depends on the type of AIHA and the severity of clinical symptoms Profound anemia, usually with a Hb level of less than g/dL, may result in cardiovascular compromise and requires erythrocyte transfusion to increase O2-carrying capacity The presence of autoantibodies often makes cross-matching blood difficult, and the patient may require transfusion with “least incompatible” blood Significant hemolytic transfusion reactions ... factors extrinsic to the RBC may lead to macroangiopathic hemolytic anemia, as with turbulent flow around a prosthetic heart valve, or microangiopathic hemolytic anemia, caused by fibrin deposition... Hematology and Oncology Problems organisms were the most frequent cause of fulminant infection in this patient population With the increased use of central venous catheters, Gram-positive organisms... now predominate.5 Antifungal therapy should be instituted in patients who fail to defervesce within to days of treatment with antibiotics Platelet transfusions should be used judiciously in an