1104 SECTION IX Pediatric Critical Care Hematology and Oncology are infrequent However, severe hemolysis occurs on rare occa sions, with hemoglobinemia and hemoglobinuria resulting in renal failure Th[.]
1104 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology are infrequent However, severe hemolysis occurs on rare occasions, with hemoglobinemia and hemoglobinuria resulting in renal failure Therefore, transfusions should be started at a slow rate, and both plasma and urine samples should be checked regularly for free Hb Patients with cold-reactive antibodies should be kept warm, and a blood warmer should be used for the transfused blood Even in the absence of transfusion, significant intravascular hemolysis may occur in patients with cold-reactive antibodies Maintaining good renal blood flow and careful monitoring of urine output in this setting may help obviate renal injury Corticosteroids appear to slow the hemolytic process, particularly in patients with IgG autoantibodies, in whom this drug class appears to inhibit Fc receptor-mediated clearance of sensitized erythrocytes The usual dosage is to mg/kg methylprednisolone administered intravenously every hours until the patient is clinically stable The patient then can be switched to oral prednisone (2 mg/kg per day for to weeks, followed by a slow taper over to months) Thrombocytopenia Related to Decreased Platelet Production Decreased platelet production may result from primary bone marrow failure states or from bone marrow infiltration by malignant cells, as in leukemia, lymphoma, and metastatic solid tumors Bone marrow suppression—a common side effect of antineoplastic therapy, including both chemotherapy and radiotherapy—frequently leads to periods of thrombocytopenia with duration dependent on the regimen Patients with hematologic malignancy, on average, receive 1.5 platelet transfusions (range, 0–3) during each chemotherapy cycle.9 In patients who have undergone hematopoietic stem cell transplantation, the time period until platelet recovery ranges from 10 to 45 days,10 and they receive to 17 platelet transfusions, on average, depending on whether they received an autologous or an allogeneic unrelated donor source.11 Despite supportive platelet transfusion therapy, bleeding continues frequently in this population, with the most common sites being minor bleeding of skin and mucous membranes Clinical manifestations include petechiae and purpura, epistaxis, gastrointestinal bleeding, hematuria, and menorrhagia Intracranial hemorrhage is an infrequent manifestation of thrombocytopenia The importance of residual bleeding despite prophylactic platelet transfusion was demonstrated in the Platelet Dose Study An analysis of the 200 patients ages 18 years or younger in the study found that bleeding (2 World Health Organization [WHO] grade) was higher in children compared with adults.12 In fact, the rate of bleeding was highest in the youngest patient cohorts; 86% in 0- to 5-year-olds, 88% in 6- to 12-year-olds, and 77% in 13- to 18-year-olds, compared with 67% in adults Pediatric patients also had more days with grade or higher WHO bleeding compared with adults There is early support for the use of antifibrinolytic therapy with either tranexamic acid or e amino caproic acid (EACA) infusion, which results in clinical improvement in ongoing bleeding and allows reduction in platelet usage.13 Guidelines for platelet transfusion vary with the underlying cause of thrombocytopenia and the patient’s clinical status Patients with primary bone marrow failure, who likely will experience prolonged thrombocytopenia, generally receive transfusions only for active bleeding because of the risk of alloimmunization In addition, exposure to multiple platelet donors may jeopardize the success of bone marrow transplantation by increasing the risk of graft rejection The threshold for transfusion may need to be higher in patients with sepsis, decreased humoral coagulants, or other risk factors In the perioperative setting, platelet counts should be maintained at greater than 50,000/dL and greater than 100,000/dL for neurologic or ophthalmologic surgery Use of ABO-compatible donors and leukoreduction diminishes the risk of platelet alloimmunization Single-donor apheresis units reduce donor exposure compared with pooled platelet concentrates, but whether such usage reduces the incidence of platelet alloimmunization remains unclear Thrombocytopenia-Related Immune-Mediated Consumption Immune-mediated platelet destruction may be caused by autoantibodies, drug-induced antibodies, or alloantibodies Alloantibodies result from exposure to polymorphic epitopes expressed on foreign platelets to which the patient has been exposed (see the previous section) Drug-induced thrombocytopenia may be suggested by the patient’s medication history, most commonly associated with heparin, which may be confirmed by laboratory tests for specific drug-associated antiplatelet antibodies In immune thrombocytopenia purpura, now renamed with the same acronym for continuity to immune thrombocytopenia (ITP), autoantibodies to platelets and megakaryocyte antigens are generated with other autoimmune disorders, immunodeficiency states, or after viral illness or immunization or without predisposing condition identified The incidence of childhood ITP ranges from to per 100,000 per year, with 25% of affected children subsequently developing chronic ITP.14 The reticuloendothelial system removes antibody-coated platelets, with the bulk of the destruction occurring in the spleen These children typically present with petechiae, purpura, bleeding from mucous membranes, and isolated thrombocytopenia There is also impaired platelet production, in which immature, large platelets enter the blood, thought to prevent serious bleeding due to the increased effectiveness of platelets The primary goal of therapy in children with ITP is to limit bleeding, especially from the central nervous system, and await spontaneous resolution, with no intervention in cases of mild or absent bleeding regardless of platelet count There is no evidence that pharmacologic intervention prevents hemorrhage, and the majority of children will undergo spontaneous remission Consensus guidelines for the definition and treatment of ITP,15 directed to slow clearance of sensitized thrombocytes in the spleen and reduce antibody production, include first-line therapy for high-risk patients or those with more than mild bleeding of a single dose or short course of corticosteroids or intravenous immunoglobulin (IVIG) Infusion of anti-Rh(D) IG (50–75 µg/kg) for individuals who have Rh(D)-positive RBCs prolongs survival of antibody-coated platelets in patients with ITP but should be avoided in patients who present with anemia As with IVIG, the major mechanism appears to include blockage of Fc receptors on reticuloendothelial cells Use of these agents usually halts bleeding and raises platelet counts to safe levels within a few days, although evidence indicating their influence on the course of the disease remains lacking Second-line agents include rituximab, splenectomy, and highdose dexamethasone Intracranial hemorrhage remains rare, and there are no data that treatment actually reduces the incidence of intracranial hemorrhage Bone marrow evaluation, CHAPTER 92 Hematology and Oncology Problems routine screening for antiplatelet antiphospholipid and antinuclear antibodies, Ig levels, and other platelet parameters are no longer considered necessary if careful history, physical examination, and review of blood count and smear are consistent with ITP Intracranial hemorrhage, a devastating but rare complication of ITP, requires immediate intervention Consequently, patients presenting with headaches, persistent vomiting, or neurologic symptoms require an emergent computed tomography (CT) scan of the head Therapy for intracranial hemorrhage in the setting of ITP includes IVIG, corticosteroids, and intermittent (2–4 IU/m2 every 6–8 hours) or continuous (0.5–1.0 IU/m2 per hour) platelet transfusions administered for life-threatening hemorrhage, with decreases in bleeding reported.16 Plasmapheresis, splenectomy, and romiplostim, a thrombopoietin receptor agonist, may be beneficial in patients who not respond to these interventions.17 Thrombocytopenia Related to Nonimmune Consumption Reduced numbers of platelets may be concomitant with cellular injury from a broad array of causes, resulting in tissue or endothelial injury Systemic response patterns involve the balance of procoagulant and anticoagulant factors, with cross-activation among coagulation, innate immunity, and inflammatory responses DIC is the result of an excess of thrombin generation by inciting factors to overwhelm the hemostatic process, which then disseminates.18 Generalized activation of the plasma coagulation pathways occurs within small blood vessels with formation of fibrin and depletion of circulating levels of clotting 1105 factors and platelets DIC usually follows a systemic insult— most often sepsis, trauma, or shock; treatment should be directed to the underlying cause Hemorrhage frequently occurs at platelet counts higher than 10,000/µL because of concomitant depletion of clotting factors, requiring platelet and plasma transfusions DIC is suspected to contribute to the development of multiorgan system failure in intensive care unit (ICU) patients, with formation of a large number of microthrombotic foci leading to organ microcirculation failure and subsequent failure of the organ itself (see Chapter 111) However, thrombocytopenia may be a marker of poor prognosis rather than a cause of ICU mortality Many common disorders are associated with development of microangiopathic hemolytic anemia and thrombocytopenia, including cancer, sepsis, organ transplantation, autoimmune disorders and eclampsia syndromes The thrombotic microangiopathy (TMA) syndromes are diverse, hereditary or acquired, and acute or chronic, but all share microangiopathic hemolytic anemia, thrombocytopenia, and organ injury.19 The four hereditary TMA disorders, Shiga toxin-mediated TMA (ST-HUS) and TMA associated with transplant, are the most common disorders in pediatric patients Most TMAs (with the exception of TTP, which is uncommon in children) share hallmarks of kidney injury, hemolytic anemia, and thrombocytopenia Increasing recognition of these syndromes has led to an awareness of specific interventions depending on the form of TMA present Depending on the type of TMA, therapeutic approach varies but may include plasma exchange, removal of inciting drug, immunosuppression, vitamin supplementation, and supportive care (Table 92.2).19 Specific management of HUS is described in Chapter 74 TABLE Primary Thrombotic Microangiopathy (TMA) Syndromes 92.2 Defect Treatment ADAMTS13 deficiency-mediated TMA (also called TTP) Homozygous or compound heterozygous ADAMTS13 Plasma infusion Complement-mediated TMA Mutations in CFH, CFI, CFB, C3, CD46, and other complement Plasma infusion or exchange, anticomplement agent Metabolism-mediated TMA Homozygous mutations in MMACHC (encoding methylmalonic aciduria and homocystinuria type C protein) Vitamin B12, betaine folinic acid Coagulation-mediated TMA Homozygous mutations in DGKE; mutations in PLG, THBD(?) Plasma infusion ADAMTS13 deficiency–mediated TMA (also called TTP) Autoantibody inhibition of ADAMTS13 activity Plasma exchange, immunosuppression Shiga toxin–mediated TMA (also called ST-HUS) Enteric infection with Shiga-toxin strain of E coli or Shigella Supportive care Drug-mediated TMA Quinine and possibly other drugs Removal of drug, supportive care Drug-mediated TMA (toxic dose–related reaction) VEGF inhibition, other mechanism Removal of drug, supportive care Complement-mediated TMA Antibody inhibition of complement factor H activity Plasma exchange, immunosuppression, anticomplement agent Hereditary Disorders Acquired Disorders HUS, Hemolytic uremic syndrome; PLG, plasminogen; THBD, thrombomodulin, TTP, thrombotic thrombocytopenic purpura; VEGF, vascular endothelial growth factor 1106 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology Thrombocytopenia caused by splenic sequestration develops in individuals with massive splenomegaly The etiology of splenomegaly includes infectious, infiltrative, neoplastic, obstructive, and hemolytic causes The Kasabach-Merritt syndrome is an association of a giant hemangioma with localized intravascular coagulation causing thrombocytopenia and hypofibrinogenemia Rare congenital thrombocytopenic syndromes include congenital amegakaryocytic thrombocytopenia, thrombocytopenia-absent radius, and Wiskott-Aldrich syndrome Bleeding in Uremia Hemorrhagic manifestations in patients with renal failure are characterized by purpura and bleeding from mucous membranes and puncture sites Gastrointestinal bleeding may contribute to morbidity and mortality in patients with end-stage renal disease Concurrent hypertension increases the risk of subdural hematoma The hemostatic defect in uremia is multifactorial, resulting in part from altered metabolism of platelets and vascular endothelial cells and from abnormal interactions between platelets and vascular endothelium.20 When uremia is present, clinical bleeding may be increased relative to the degree of thrombocytopenia resulting from secondary platelet dysfunction IV administration of desmopressin acetate (0.3 mg/kg over 30 minutes) improves platelet dysfunction caused by uremia within hour, with an effect for to hours.21 Tachyphylaxis may occur after two to three doses IV or transdermal conjugated estrogens or oral estrogens cause slower but more sustained improvements in bleeding time.22 Dialysis results in improved platelet function through reduction of azotemia When severe anemia is present, platelets travel closer to the midstream and are less likely to interact with the vascular endothelium In addition, RBCs exert metabolic effects on platelets by enhancing adenosine diphosphate and thromboxane A2 release Therefore, use of red cell transfusions or erythropoietin to increase the hematocrit to 30% helps to correct the bleeding time.23 Further increase in hematocrit increases the risk of thrombosis, particularly of arteriovenous shunts and the extracorporeal hemodialysis circuit Oncologic Emergencies Tumor Lysis Syndrome Tumor lysis syndrome (TLS) is characterized by metabolic abnormalities—including hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia—that have resulted from the rapid death of tumor cells either spontaneously or after the institution of chemotherapy.24,25 These metabolic derangements can lead to renal failure, arrhythmias, seizures, and potentially death.26 Careful monitoring and rigorous attention to organ function may help to obviate the majority of complications from this syndrome Risk factors for developing TLS include the level of tumor burden and its sensitivity to the antitumor agents, new-onset disease, preexisting renal dysfunction, exposure to medications that increase uric acid levels, and dehydration.27 In children, hematologic malignancies—such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and Burkitt lymphoma—account for the majority of cases of TLS, although it is also reported in solid tumors such as neuroblastoma.28 On cell lysis, tumor cells release normal or supranormal quantities of many types of intracellular contents into the circulation, including potassium, nucleic acids, inorganic phosphates, and proteins In patients with high tumor burden and highly effective chemotherapy, this massive release of cellular contents can overwhelm the body’s normal homeostatic mechanisms for processing these substances, resulting in laboratory and then clinical TLS.25 The bedrock of therapy is volume expansion to ensure adequate end-organ perfusion and a robust urine flow rate to optimize excretion Sometimes, in order to protect end organs, additional medications are needed to alter uric acid production or to more rapidly bind or eliminate abnormal electrolytes Hyperkalemia Hyperkalemia is the most life-threatening derangement of TLS and must be addressed emergently Levels of potassium greater than 6.5 mmol/L may lead to peaked T waves and widening of the QRS complex that can progress to disorganized ventricular rhythms and cardiac arrest Other symptoms of hyperkalemia include irritability, fatigue, muscle weakness and cramps, paresthesias, nausea, emesis, and diarrhea Therapy includes oral or rectal cation exchange resins, IV calcium (gluconate or chloride) to antagonize the action of potassium on the cardiac myocyte, and sodium bicarbonate to correct acidosis in order to improve the gradient of potassium into cells Diuretic therapy or dialysis may also be used (see Chapter 75) Hyperphosphatemia/Hypocalcemia Excess phosphate released during TLS is initially excreted in the urine by decreased tubular reabsorption, but this mechanism is limited and is impaired by renal injury As phosphate levels rise, the phosphate avidly binds calcium, depleting serum calcium levels and potentially precipitating as calcium phosphate crystals in renal tubules, exacerbating renal dysfunction Crystallization appears to increase when the calcium phosphate multiple (total calcium [mg/dL] multiplied by the phosphate level [mg/dL]) exceeds 70 and when the urine has been alkalinized Thought should be given to the balance between alkalinized IV fluids to optimize uric acid excretion and nonalkalinized fluids to optimize phosphate excretion Hyperphosphatemia in spite of adequate hydration may respond poorly to oral phosphate binders and may require renal replacement therapy With elevated phosphate levels, calcium levels can become quite low, but asymptomatic hypocalcemia should not be treated Hypocalcemia associated with tetany, seizures, or dysrhythmias should be treated until symptom resolution but not to normal biochemical parameters Counterintuitively, asymptomatic hypocalcemia is best addressed by treating hyperphosphatemia Hyperuricemia Uric acid is the final product of purine nucleotide metabolism (Fig 92.1) prior to excretion in the urine; its production is dependent on the enzyme xanthine oxidase Hyperuricemia injures renal tubules, mostly through deposition of urate crystals in renal tubules, causing micro-obstruction However, there are some experimental and clinical data that uric acid may alter kidney hemodynamics through vasoconstriction and possibly have direct toxic effects on the nephron through various mechanisms, especially in the context of dehydration and administration of nephrotoxic medications.29 Initial treatment of hyperuricemia is accomplished by optimizing elimination through alkalization of the urine to improve uric acid solubility and decreasing uric acid production through allopurinol The solubility of uric acid is highly pH dependent With an increase in pH from to 7, urine concentrations of uric acid increase from 15 mg/dL to 200 mg/dL.30 Allopurinol, CHAPTER 92 Hematology and Oncology Problems Adenine Guanine Hypoxanthine Solubility at pH 5.0 0.7 mg/mL Xanthine 0.13 mg/mL Xanthine oxidase Allopurinol Uric acid 0.15 mg/mL Allantoin + CO2 + H2O2 mg/mL Rasburicase • Fig 92.1 Purine degradation pathway and mechanism of action of allopurinol and rasburicase Uric acid is the end product in humans CO2, Carbon dioxide; H2O2, hydrogen peroxide (Modified from Wilson FP, Berns JS Tumor lysis syndrome: new challenges and recent advances Adv Chronic Kidney Dis 2014;21[1]:18–26.) a xanthine analogue, inhibits the conversion of xanthine and hypoxanthine to uric acid by competitively blocking xanthine oxidase and has been shown to reduce the incidence of obstructive uropathy caused by uric acid.31,32 Allopurinol is used to prevent hyperuricemia, but it cannot lower elevated uric acid levels that preceded therapy Hyperuricemia that persists after volume expansion is dangerously elevated on presentation or occurs while on allopurinol requires aggressive therapy Urate oxidase, a lytic enzyme that is present in most nonprimate mammals, cleaves uric acid to more soluble allantoin, which is easily eliminated Rasburicase, a recombinant urate oxidase, is very expensive but highly effective at reducing uric acid levels rapidly and is recommended for use in any patient who has developed clinical TLS while on allopurinol.27 Rasburicase is contraindicated in patients with a known G6PD deficiency (certain patients of African American, Mediterranean, or Southeast Asian descent) and in pregnant or lactating females.33 While rasburicase may be effective in reducing serum uric acid levels and is recommended by experts and guidelines for high-risk patients, a 2017 Cochrane review concluded that it was unclear whether urate oxidase reduces clinical TLS, renal failure, or mortality, although the quality of evidence was rated as very low to low.33a Hyperleukocytosis Hyperleukocytosis, defined as a white blood cell (WBC) count greater than 100,000/µL, is seen in 5% to 20% of children diagnosed with leukemia, most often in patients with ALL.34 Hyperleukocytosis causing symptomatic leukostasis usually occurs with WBC counts greater than 200,000/µL in AML, greater than 300,000/µL in ALL, and greater than 600,000/µL in chronic myeloid leukemia.35 Leukostasis in AML is purported to occur at lower concentrations of WBC levels because myeloblasts and monoblasts tend to be larger and more rigid than lymphoblasts and granulocytes and are more likely to obstruct vessels The viscosity of the blood is dependent on the leukocyte and erythrocyte volumes as well as the deformability of the cells.36 Substantial increases in 1107 WBC counts produce aggregates of leukocytes, which may obstruct small blood vessels Leukostasis results in local hypoxia, and invasion of the blood vessels by leukemic cells can produce organ and vascular damage or hemorrhage Leukemic cells’ variable expression of adhesion molecules and cytokines, such as IL-1 and tumor necrosis factor-a, may explain the variability of WBC counts and clinical presentation of patients with leukostasis.34 Children with hyperleukocytosis have higher rates of morbidity and mortality than other children with leukemia, but particularly are at risk for early death: AML and hyperleukocytosis 16.9% and ALL and hyperleukocytosis, 4% risk of early death.37 Hyperleukocytosis most frequently causes neurologic, pulmonary, and metabolic pathophysiology Signs and symptoms of neurologic leukostasis may include headache, altered mental status, visual disturbances, or seizures The most concerning neurologic complication is an intracranial hemorrhage, which typically is limited to the white matter The risk for intracerebral hemorrhage can persist even after reduction of the WBC count Clinicians should consider urgent neuroimaging with any changes in a patient’s neurologic status, with judicious use of IV contrast Central nervous system hemorrhage with high WBC counts occurs in 5% to 33% of patients with AML and hyperleukocytosis, usually correlating with the degree of hyperleukocytosis.36 Respiratory symptoms found with pulmonary leukostasis may include dyspnea, hypoxemia, respiratory failure, and acute respiratory distress syndrome Arterial measurement of oxygenation should be interpreted with caution because pseudohypoxemia from so-called leukocyte larceny can occur even with samples immediately placed on ice Pulse oximetry may be a more reliable measure of oxygenation Chest radiograph findings of pulmonary leukostasis may be normal or reveal diffuse interstitial infiltrates Immediate cytoreduction is indicated when excessive O2 metabolism of leukocytes causes tissue hypoxemia Elevated serum lactate levels have been described as an early sign of microcirculatory failure.34 Cytoreduction by leukapheresis, exchange transfusion, or other methods may modulate cell-cycle distribution and nucleoside transporters in leukemic cells by increasing the fraction of the S-phase Therapy for hyperleukocytosis has remained challenging to rigorously study given the different types of leukemia and lack of multicenter trials Diuretic therapy and PRBC transfusion both increase viscosity and should be strictly avoided Concurrent thrombocytopenia and hyperleukocytosis increase risk of death from bleeding complications Aggressive therapy with fresh frozen plasma and vitamin K to correct coagulopathy and maintenance of platelet count greater than 20,000/µL are critical Hydration, alkalinization, and allopurinol have been used in patients with WBC counts higher than 100,000/µL.35 More aggressive therapies must be considered for symptomatic patients, especially those with laboratory evidence of hypoxia or ischemia, or in certain patients depending on malignancy type and WBC count Exchange transfusion, leukapheresis, or chemotherapy can be used to rapidly lower WBC count Initial enthusiasm for reduction of WBC burden by leukapheresis (33%–53% reduction of WBC fraction in first procedure) and single-institution reports of low rates of complications suggested that mechanical removal of WBC burden with leukapheresis was reasonable.37–39 No randomized trials of cytoreduction have been performed; although a reduced incidence of electrolyte abnormalities has been shown, no improvement in pulmonary status, central nervous system outcome, or mortality has been demonstrated.37 Complications of leukapheresis include difficulty with vascular access, rapid rebound of WBC count, and the need for anticoagulation One 1108 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology large series in new ALL patients with hyperleukocytosis found no long-term benefit to leukapheresis compared with conservative measures with frequent complications, recommending discontinuation of the practice.40 However, risk of early death in hyperleukocytosis on presentation with AML, associated with M4/M5 type, was improved with removal of cell burden by either exchange transfusion or leukapheresis, suggesting that specific populations may benefit from invasive reduction strategies.41 No beneficial role has been demonstrated for use of corticosteroids or emergency cranial radiation.36 Leukapheresis should never be undertaken in a patient with suspected acute promyelocytic leukemia due to risk of hemorrhagic complications Spinal Cord Compression Compression of the spinal cord by malignancy occurs uncommonly but still represents an important cause of morbidity in children, affecting between 2.7% to 5.0% of children with cancer.42–44 Most frequently, compression occurs as metastatic disease spreads rather than as primary spinal cord tumors themselves Ewing sarcoma, neuroblastoma, and primitive neuroectodermal tumors appear to be the most frequent diagnoses, although compression may be found with lymphoma, nephroblastoma, and germ cell tumors.42 Most cord compression results from epidural compression due to extension of paravertebral tumor through the intervertebral foramina or, less commonly, extension of the tumor in the vertebral column Compression of the vertebral venous plexus by epidural tumor causes vasogenic cord ischemia, edema, venous hemorrhage, and myelin loss.44 Spinal cord compression usually localizes to the dorsal and lumbosacral regions (42% each) Patients frequently develop radicular or central back pain, motor dysfunction, gait dysfunction, sphincter abnormalities, and alteration in sensation Such findings represent harbingers of potential permanent loss of neurologic function, necessitating emergent evaluation, including magnetic resonance imaging (MRI) Management of tumor compression of the spinal cord requires emergent medical action of a multidisciplinary team comprised of pediatric oncology, neurosurgery, orthopedics, neurology, pathology, and radiology Treatment requires mg/kg dexamethasone intravenously over 30 minutes and next mandates a decision between immediate surgical decompression, radiation therapy, or chemotherapy This decision is influenced by a number of factors, including the presence of a histologic diagnosis, likelihood of response to chemotherapy or radiotherapy, and degree and rate of progression of neurologic deficit Although controversy exists, decompressive laminectomy may be indicated for tumors without a diagnosis; patients with small cell tumors with rapid neurologic deterioration or complete loss of motor function; and sarcoma, with the exception of osteogenic sarcoma Laminectomy in children often leads to scoliosis, kyphosis, and anterior subluxation that may require subsequent orthopedic interventions after the initial surgery These long-term consequences need to be balanced with the short-term risks Among children with complete sensory and motor loss below the level of spinal cord compression, 30% to 60% of treated children experience neurologic recovery.44 Acute Airway Compromise in Anterior Mediastinal Tumors Childhood mediastinal masses pose difficult diagnostic and therapeutic challenges Such masses often produce few symptoms until they have occluded a substantial portion of the trachea, main stem bronchi, or the superior vena cava (SVC) Complete airway occlusion in these children represents a potentially fatal complication, a risk that increases at the time of sedation for diagnostic procedures An estimated 9% to 15% of pediatric patients with anterior mediastinal masses and airway obstruction have been reported to develop life-threatening complications with anesthesia.45–47 Since the 1990s, increased awareness of the potential for airway or cardiovascular collapse in pediatric patients with anterior mediastinal masses has led to improved management Major airway complications are now more likely to occur in the postanesthetic period SVC syndrome, left atrial compression, and pericardial effusion may lead to a state of fixed cardiac output Mediastinal masses are classified by their anatomic compartment; anterior mediastinal masses represent 46% of all such masses in children.48 The most common tumors found in the anterior mediastinal compartment include hematologic malignancies: T-cell lymphoblastic leukemia, Hodgkin disease, and T-cell lymphoblastic non-Hodgkin lymphoma.49,50 Children with an anterior mediastinal mass often present with nonspecific findings, including orthopnea, dyspnea, cough, pleural effusion, wheezing, SVC syndrome, pain, and stridor.51 Mediastinal masses are far more common in older children and teenagers than in children younger than years Barking cough and stridor in an older child or teenager rarely occur with croup and therefore require further investigation Important risk factors for airway compromise include CT findings of a greater than 50% decrease in a cross-sectional area of the trachea, peak expiratory flow less than 50% of predicted value, anterior mediastinal mass, tracheal compression, main stem bronchus compression, larger median mediastinal mass ratio, lymphoma, vena cava syndrome, pericardial effusion, pleural effusion, history of recurrent chest infections, stridor, orthopnea, cough, wheeze, and shortness of breath.45,46 The predictive value of these risk factors remains controversial, however Unfortunately, compression at the level of the carina or bronchi may contribute appreciably to respiratory compromise, even in patients with a crosssectional area above 50% of predicted.50 A CT scan will provide evidence of airway compression at a tracheal or bronchial level as well as the existence of exacerbating factors such as pleural effusion, which may limit a patient’s physiologic reserve The preoperative evaluation of patients with critical airway from compression by an anterior mediastinal mass should include an experienced multidisciplinary pediatric team made up of an oncologist, anesthesiologist, interventional radiologist, surgeon, and intensivist CT provides the most useful, rapid step in the assessment for airway compromise; unfortunately, severe or rapidly progressive symptoms may preclude lying supine for the scan (Fig 92.2) In such cases, the risks and benefits of performing a diagnostic procedure under local anesthesia with ultrasound guidance, beginning preoperative treatment prior to pathologic diagnosis, or proceeding with general anesthesia need to be discussed by the team and with the family Empiric treatment is controversial because it can distort the histopathologic appearance and hinder a definitive diagnosis However, in one study, an accurate diagnosis was made in 95% of patients receiving corticosteroids prior to biopsy.49 Bone marrow or lymph node biopsy and pleural fluid analysis may be helpful in patients who are not unstable Complete blood count, a-fetoprotein, b-human chorionic gonadotropin, and lactate dehydrogenase levels should be obtained Image-guided needle biopsy performed under local anesthesia for mediastinal mass or lymph node by a skilled interventional radiologist remains the diagnostic test of choice.50 ... Chronic Kidney Dis 2014;21[1]:18–26.) a xanthine analogue, inhibits the conversion of xanthine and hypoxanthine to uric acid by competitively blocking xanthine oxidase and has been shown to reduce... CHAPTER 92 Hematology and Oncology Problems Adenine Guanine Hypoxanthine Solubility at pH 5.0 0.7 mg/mL Xanthine 0.13 mg/mL Xanthine oxidase Allopurinol Uric acid 0.15 mg/mL Allantoin + CO2 + H2O2... syndromes are diverse, hereditary or acquired, and acute or chronic, but all share microangiopathic hemolytic anemia, thrombocytopenia, and organ injury.19 The four hereditary TMA disorders,