Diagnosis Supportive Care in Pediatric Oncology irantextbook.ir 93df
8.7 Management
8.7.1 Prevention
Although several professional organizations have published guidelines for VTE prophylaxis in adult oncology patients, evidence-based guidelines for prevention in children with cancer are lacking. The American Society of Clinical Oncology ASCO, the National Comprehensive Cancer Network NCCN, and others have recommended prophy- lactic anticoagulation for all hospitalized oncol- ogy patients and for high-risk surgical oncology patients, but not for ambu latory cancer patients with or without CVCs Khorana et al. 2009 . These guidelines, developed for adults with a very differ- ent range of malignancies, comorbidities, and treat- ments than seen in children, are clearly not directly applicable to the pediatric oncology population. Evidence from clinical trials of thromboprophy- laxis in children with cancer is limited and generally inconclusive. The Prophylaxis of Thromboembolism in Kids PROTEKT trial randomized 186 children with CVCs, half with cancer, to receive reviparin LMWH prophylaxis or standard care. There was no difference in the rate of TE or adverse events, but the study was underpowered and terminated early due to slow accrual Massicotte et al. 2003 . The PARKAA trial randomly assigned 85 patients treated for ALL on contemporary North American protocols to receive weekly infusions of AT during induction with asparaginase. Twenty-eight percent of patients treated with AT developed TE versus 37 in the control group, but the study was under- powered to show a signifi cant difference, and no difference was seen in markers of endogenous thrombin generation Mitchell et al. 2003a . Supplementation with fresh frozen plasma FFP has been shown to be ineffective in correcting hemostatic parameters in children treated with asparaginase Nowak-Göttl et al. 2009 . Ruud et al. 2006 reported no reduction in the incidence of CVC-related jugular thrombosis among 62 children with cancer in a randomized, placebo-controlled study of low-dose warfarin prophylaxis. Several small cohort studies and case series have reported various methods of thromboprophy- laxis. Harlev et al. 2010 screened 80 children with ALL for inherited thrombophilia and pro- vided enoxaparin prophylaxis during induction for 18 patients with prothrombin gene mutation or factor V Leiden heterozygosity. Six patients 7.5 developed TE, half of whom had PT muta- tion and were receiving prophylaxis. Elhasid et al. 2001 prescribed enoxaparin prophylaxis during asparaginase treatment to 41 consecutive children with ALL and reported no episodes of TE and no bleeding but with no comparative control group. Meister et al. 2008 reported no episodes of TE in 41 children treated on BFM ALL trials with AT supplementation and enoxaparin prophylaxis in induction and reinduction versus 13 of 71 patients in an earlier cohort treated on the same protocol with AT supplementation alone. Mitchell et al. 2010 recently reported validation of a pre- dictive model for identifying the risk of TE in chil- dren with ALL treated on Berlin-Frankfurt-Munster BFM, Cooperative Acute Lymphoblastic Leukemia COALL and French Acute Lymphoblastic Leukemia FRALLE induction protocols. The model incorporates factors includ- ing concomitant asparaginase with steroids, pres- ence of a CVC and genetic thrombophilia. Eight high-risk patients received enoxaparin prophylaxis during induction at their physicians’ discretion and one developed TE as compared with eight events among 11 high-risk patients who received no thromboprophylaxis Mitchell et al. 2010 . Of note, this predictive model was protocol specifi c no high-risk patients on the FRALLE protocol experienced TE and would require further study before application in the context of current North American or other protocols. The small size, variability and design of these studies constitute signifi cant limitations. At this time, there is insuffi cient evidence to recommend routine thromboprophylaxis in children with can- cer. The American College of Chest Physicians ACCP, in its 2012 clinical practice guidelines for antithrombotic therapy in children and neo- nates, recommends against the use of routine sys- temic thromboprophylaxis for children with short- or medium-term CVCs Monagle et al. 2012 . Without evidence to support any benefi t of prophylactic FFP or AT replacement, routine screening of coagulation tests during ALL induc- tion therapy is not recommended. Similarly, routine screening of children with ALL or other malignancies for inherited thrombophilia is not currently advised outside of a clinical trial, but may be appropriate for patients with a confi rmed family history of a high-risk genetic defect Astwood and Vora 2011 . Secondary screening may be considered for patients at the time of diagnosis with symptomatic TE. At our institution, patients who develop a non-CVC-associated thrombosis are usually tested for factor V Leiden, prothrombin G20210A mutation, protein C and S defi ciency, AT defi ciency, lipoprotein a, fast- ing serum homocysteine, factor VIII, and antiphospholipid antibodies. Prophylaxis may be considered for select groups of patients at increased risk, including those with known inherited prothrombotic defects who are receiving asparaginase, adolescents undergoing major surgery or prolonged immobili- zation, and patients with a previous history of TE with other risk factors such as surgery or disease relapse Wiernikowski and Athale 2006 . Evidence-based data to support these consider- ations in pediatric patients are lacking.8.7.2 Treatment
LMWH is the anticoagulant of choice for most pediatric patients, offering advantages of reduced monitoring, minimal drug or diet interactions, and a favorable safety profi le Monagle et al. 2012 . The REVIVE reviparin in childhood venous thromboembolism trial is the only randomized study of LMWH in pediatrics Massicotte et al. 2003 . This trial compared revi- parin to unfractionated heparin UH and oral anticoagulation in children with TE but termi- nated early due to slow enrollment. Though underpowered, it contributed to other accumulat- ing evidence that LMWH is safe and effective treatment for TE in pediatrics Massicotte et al. 2003 . Alternatives include UH, which may be preferred initially over LMWH in circumstances of increased bleeding risk where rapid reversal may be necessary. Systemic or catheter-directed thrombolysis with tissue plasminogen activator tPA may be considered in some cases of high- risk thrombosis, though experience in children, particularly in the setting of malignancy, is very limited. The 2012 ACCP guidelines suggest tPA use only for life- or limb-threatening thrombosis in children Monagle et al. 2012 . Warfarin is often problematic in children with cancer because of problems related to dosing, drug interactions, vitamin K variability, and diffi culty of oral administration during episodes of nausea and mucositis. It is generally not recommended for children during treatment for cancer, but can be considered for long-term or indefi nite anticoagu- lation, when required. In their 2012 guidelines, the ACCP suggests that children with cancer who develop TE follow the general recommendations for children with TE, using LMWH for a minimum of 3 months and until the precipitating factor has resolved Monagle et al. 2012 . In the acute setting of symptomatic TE, LMWH such as enoxaparinParts
» Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Introduction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» History and Physical Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Defi ning the Risk for Serious
» Initial Laboratory Evaluation Diagnostic Evaluation
» Chest Radiography CXR A supine CXR may identify pleural effusions,
» Computed Tomography CT Radiographic Imaging
» Magnetic Resonance Imaging MRI
» Positron Emission Tomography PET
» Aspergillus Galactomannan GMN Biomarkers for Invasive
» 1,3-β- Biomarkers for Invasive
» Polymerase Chain Reaction PCR
» Viral Studies Diagnostic Evaluation
» Invasive Procedures: Diagnostic Evaluation
» Adult FN Guidelines Empiric Management
» Monotherapy Versus Combination Therapy
» Which Monotherapy to Choose A Cochrane review of antipseudomonal beta-
» Alterations in Initial Empiric FN Antibiotic Management
» Outpatient Management of FN Although there remains a lack of one uniform
» Choice of Empiric Antifungal Therapy
» Duration of Antimicrobial Empiric Management
» Endovascular Sources Empiric Management
» Adjunctive Treatment Empiric Management
» Emergence of Resistant Empiric Management
» Red Blood Cell Administration
» Granulocyte Transfusion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hemolytic Transfusion Risks of Blood Product
» Infection and Sepsis Risks of Blood Product
» Allergic Reactions Risks of Blood Product
» Febrile Nonhemolytic Risks of Blood Product
» Transfusion-Related Acute Risks of Blood Product
» Transfusion-Associated Risks of Blood Product
» Iron Overload Risks of Blood Product
» Laboratory Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» General Management Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Alkalinization Urinary alkalinization has been a long-standing
» Allopurinol Allopurinol inhibits xanthine oxidase, an enzyme
» Rasburicase Rasburicase, recombinant urate oxidase, converts
» Renal Interventions Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pathophysiology Superior Vena Cava
» History and Physical Exam SVCSSMS should be suspected in a patient
» Imaging Studies The diagnosis of SVCSSMS is often made on
» Other Studies Tissue is required to make a defi nitive diagnosis
» Treatment Superior Vena Cava
» History and Physical Exam Small pericardial effusions are frequently asymp-
» Imaging and Other Studies The presence of a pericardial effusion can be
» History and Physical Exam Many patients with small pleural effusions are
» Imaging Studies When a pleural effusion is suspected, a chest
» History and Physical Exam Patients with pheochromocytoma typically have
» Laboratory Studies The diagnosis of pheochromocytoma is best made
» Imaging Studies Clinical Presentation
» Pulmonary Leukostasis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Presentation Spinal Cord Compression
» Differential Diagnosis Spinal Cord Compression
» Imaging MRI of the spine can help narrow the differential
» Surgery Surgery in spinal cord compression can be uti-
» Radiation Therapy The advantages of external beam radiation ther-
» Outcomes Spinal Cord Compression
» Presentation Altered Mental Status
» Initial Management Altered Mental Status
» Metabolic The metabolic causes of AMS or seizure in pedi-
» Chemotherapy-Associated Neurotoxicity Differential Diagnosis
» Posterior Reversible Encephalopathy Syndrome
» Outcomes Altered Mental Status
» Initial Management Increased Intracranial
» Soft Tissue A large meta-analysis of published data suggests
» Cerebrospinal Fluid Hydrocephalus is an excess of CSF within the
» Hemorrhage and Thrombosis Differential Diagnosis
» Idiopathic Intracranial Hypertension Differential Diagnosis
» Presentation of Stroke Cerebrovascular Disease
» Differential Diagnosis Cerebrovascular Disease
» Etiology of Stroke in Pediatric
» Ischemic Stroke After an ischemic stroke is diagnosed, the patient
» Hemorrhagic Stroke Hematomas can expand over several hours from
» Acute Lymphoblastic Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Myelogenous Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Acute Promyelocytic Leukemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Chronic Myelogenous Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Tumor Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Leukapheresis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Hyperhydration Other Treatment Modalities
» Hydroxyurea Other Treatment Modalities
» Cranial Irradiation Other Treatment Modalities
» Pseudohyperkalemia Hyperleukocytosis has been noted to cause pseudo-
» Pseudohypoxemia Due to the rapid consumption of oxygen by leu-
» Pseudohypoglycemia Consumption of glucose by excess leukocytes
» Pseudothrombocytosis Leukemic blast lysis can lead to cell fragmenta-
» Transfusion Practice with Other Supportive Care
» Anesthetic Procedures Other Supportive Care
» Neutropenic Enterocolitis Gastrointestinal Infection
» Perirectal Abscess Gastrointestinal Infection
» Gastrointestinal Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Pancreatitis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Bowel Obstruction Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Abdominal Compartment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» ALL Risk Factors Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Other Malignancies Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Central Venous Catheters Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diagnosis Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nociceptive Pain Types of Pain
» Neuropathic Pain Types of Pain
» World Health Organization Pharmacologic Treatment
» Intermittent Opioid Use Pharmacologic Treatment
» Long-Acting Opioids Pharmacologic Treatment
» Breakthrough Dosing Pharmacologic Treatment
» Opioid Rotation Pharmacologic Treatment
» Patient-Controlled Analgesia Pharmacologic Treatment
» Constipation Side Effects of Opioids
» Nausea and Vomiting Nausea and vomiting are rare opioid side effects
» Pruritus Pruritus is a common side effect of opioid use
» Sedation Side Effects of Opioids
» Confusion and Agitation Renal and hepatic function should be checked
» Respiratory Depression When dosed appropriately, opioids rarely result
» Myoclonus Patients receiving very high doses of opioids for
» Urinary Retention Urinary retention can be caused by any opioid but
» Calcium Channel Blockers Neuropathic Pain
» Serotonin and Norepinephrine Neuropathic Pain
» Tricyclic Antidepressants Neuropathic Pain
» Interventional Techniques Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vincristine-Related Peripheral Oncology-Specifi c Pain
» Osteonecrosis Oncology-Specifi c Pain
» Post-lumbar Puncture Oncology-Specifi c Pain
» Mucositis Pain Oncology-Specifi c Pain
» Pathophysiology of Emesis Chemotherapy-Induced
» Principles of Emesis Control in the Cancer Patient
» Emetogenicity of Chemotherapy Chemotherapy-Induced
» Dopamine Receptor Antagonists Classes of Antiemetics
» Corticosteroids Classes of Antiemetics
» Cannabinoids The plant Cannabis contains more than 60 differ-
» Other Antiemetic Agents Antihistamines
» Alternative Therapies Ginger Classes of Antiemetics
» Management of CINV Management of CINV Table
» Special Considerations Anticipatory Nausea and Vomiting
» Radiation-Induced Nausea Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Initiation The initiation stage occurs immediately following
» Primary Damage Response Pathophysiology of Oral Mucositis
» Signal Amplifi cation Pathophysiology of Oral Mucositis
» Ulceration Ulceration is the phase with the most clinical sig-
» Healing Pathophysiology of Oral Mucositis
» Clinical Course of Oral Mucositis
» Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Palifermin Prevention and Treatment
» Low-Level Laser Therapy Prevention and Treatment
» Glutamine Prevention and Treatment
» Cryotherapy Prevention and Treatment
» Oral Care Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Infections Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Nutrition Assessment Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Dietary Counseling Nutrition Intervention
» Appetite Stimulants Nutrition Intervention
» Enteral Tube Feeding Nutrition Intervention
» Parenteral Nutrition Nutrition Intervention
» Nutrition and Survivorship Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Management of Neutropenia Hematologic Toxicity
» Management of Thrombocytopenia Hematologic Toxicity
» Management of Anemia Hematologic Toxicity
» Somnolence Syndrome Central Nervous System
» Lhermitte’s Sign Central Nervous System
» Skin Complications Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Oral Mucositis Head and Neck
» Ear Complications Head and Neck
» Laryngeal Complications Head and Neck
» Dysphagia and Esophagitis Gastrointestinal
» Nausea, Vomiting and Anorexia
» Pneumonitis Major Organ Infl ammation
» Pericarditis Major Organ Infl ammation
» Hepatitis Major Organ Infl ammation
» Nephropathy Major Organ Infl ammation
» Cystitis Major Organ Infl ammation
» Risk Stratifi cation Prevention of Bacterial
» Adult Data Antimicrobial Approaches
» Pediatric Data Data regarding the utility of bacterial prophylaxis
» Risks of Prophylaxis Prevention of Bacterial
» Guidelines and Current Usage of Antibacterial Prophylaxis
» Protocols for Line Placement and Care
» Antibiotic and Ethanol Locks
» Chlorhexidine Cleansing Chlorhexidine gluconate CHG is a bactericidal
» Future Directions Prevention of Bacterial
» Risk Stratifi cation Prevention of Fungal
» Approaches to Antifungal Prophylaxis
» Guideline Recommendations for Antifungal Prophylaxis
» Limitations of Current Options for Antifungal Prophylaxis
» Risks of Prophylaxis Prevention of Fungal
» Biomarkers Prevention of Fungal
» Future Directions Prevention of Fungal
» Risk Stratifi cation Prevention of Pneumocystis
» Approaches to PCP Prophylaxis
» Summary of the Recommendations
» Future Directions Prevention of Pneumocystis
» Postexposure Chemoprophylaxis Prevention of Viral Infections
» Suppressive Therapy Prevention of Viral Infections
» Future Directions Prevention of Viral Infections
» Hand Hygiene Infection Control Practices
» Mandatory Vaccination Infection Control Practices
» Hospital Isolation Practices Infection Control Practices
» Visitor Screening Policies Infection Control Practices
» Work Restriction Infection Control Practices
» Cytomegalovirus CMV Status of Transfused Blood
» Treatment of Myelosuppression with
» Prevention of Febrile Neutropenia, Delay
» Treatment of Febrile Neutropenia
» Treatment of Myelosuppression Clinical Usage of Myeloid Growth Factors
» Comparison of Granulocyte Colony-Stimulating Factor
» Optimal Dosing Adult guidelines recommend dosing of 5 mcgkg
» Route of Administration Optimal Administration of Colony-Stimulating Factors
» Optimal Timing Optimal Administration of Colony-Stimulating Factors
» Erythropoietin Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Interleukin-11 Platelet Growth Factors
» Thrombopoietin Receptor Agonists Platelet Growth Factors
» Immune Status Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Status During Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immune Recovery After Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Immunization Practice Prior Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Diphtheria, Tetanus, and Acellular Pertussis
» Pneumococcal Conjugate Vaccine Recommendations
» Hemophilus Infl uenzae Type b
» Inactivated Infl uenza Vaccine Although in a Cochrane review Goossen et al.
» 2009 H1N1 Pandemic Vaccine Seven studies have reported on effi cacy of the
» Live Attenuated Infl uenza Vaccine
» Meningococcal Conjugate Vaccine Recommendations
» Varicella Zoster Virus Recommendations
» Recommendations Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Treatment of Hypogammaglobulinemia Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Vaccination of Household Contacts
» Peripherally Inserted Central Catheter
» External Tunneled Central Venous Catheter
» Implanted Port Types of Central Venous
» Catheter Insertion Supportive Care in Pediatric Oncology irantextbook.ir 93df
» Exit Site Infection Infection
» Prevention of Infection Infection
» Drug Precipitate or Lipid Residue Occlusion Thrombotic Occlusion
» Evaluation of Catheter- Related Thrombosis
» Treatment of Catheter- Related Thrombosis
» Special Considerations During Anticoagulation Therapy
» Contraindications of Anticoagulant Therapy
» Skin Antisepsis Catheter Maintenance
» Central Venous Catheter Dressings
» Hub Care Catheter Maintenance
» Central Venous Catheter Flushing and Locking
» Chlorhexidine Bathing Chlorhexidine has been shown to be effective in
» Antiseptic Needleless Connectors and Antiseptic
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