Differential diagn: Congenital red cell aplasia (Diarnond—Blackfan anemia) Chronic parvovirus B19 viremia Immune-mediated pure red cell aplasia Other congenital syndromes of bone marrow failure Differential diagnosis of red cell aplasia in infancy + Congenital red cell aplasia (Diarnond-Blackfan anemia) + Early presentation of transient erythroblastopenia of childhood + Congenital parvovirus B19 infection * Alloimmune erythroid hypoplasia (maternal anti-Kell) Practice point Bone marrow transplant in Diamond-Blackfan anemia: Table 5.3 Factors affecting iron absorption of nonheme iron from the gastrointestinal tract. Increased absorption Acids: Vitamin C Hydrochloric acid Solutes Sugars ‘Amine acids (rneats) Decreased absorption Alkalis Antacids Pancreatic secretions Hypochlorhydria Precipitating agents (vegetables) Phytates PhosphatesTable 5.4 Sequence of detectable reduction in iron stores as iran deficiency anemia develops. 1 Serum ferritin Reduced iron stores 2. Plasrra transferrin receptor 3 Plasrrairon 4. Total iron-binding capacity 5 Marrow sideroblast percentage 6 Red blood cell protoporphyrins 7 Red blood cell morphology tron deficiency anemia Table 5.10: Etiology of iron overioad. Increased gastrointestinal absorption Hereditary hemochromatosis Erythroid hyperplasia with ineffective erythropoiesis BeThalassernia major B-Thalassernia intermedia Hemoglobin €/pi-thalassemia ‘Congenital dyserythropoietic anemias Pyruvate kinase deficiency Sideroblastic anernias ‘Atransferrinemias and other rare disorders of iron transport Repeated red call transfusions Perinatal ron overload Hereditary tyrosinemia (hypenethioninemia) Zellweger syndrome (cerebrohepatorenal syndrome) Neonatal hemochromatosis Focal iron sequestration Idiopathic hemochromatosis: Hallervorden-Spatz syndrome Chronic hemoglobinuriaTable 5.6 Common causes of hypochromic micracytic anemia related to stage of childhood. ‘Neonatal period: iron deficiency unlikely Rest of childhood: iron deficiency most common cause Infancy and early childhood Dietary Prematurity Low birthweight Later childhood Dietary Bleeding Puberty Dietary Bleeding Increased demands: (i) menstruation; (ii}each 1kg of weight gain =80 mL blood and requires 45 mg of iron Table 5.111 Complications of iron overload and the effect of chelation ‘therapy. Effect of chelation therapy Reversibility of ‘Complication Protection established disease Liver Yes Yes Heart Yes Yes Endocrine Growth Yes Yes Hypogonadism Yes No Diabetes mellitus Yes No Hypothyroidism: Yes No Hypoparathyroidism Yes No Arthropathy ‘Unknown Infections INo (Yersinia seen with chelation therapy)Table 6.1. Acquired causes of cobalamin deficiency. Nutritional Matemal deficiency Vegan Malabsorption Gastric Pemicious anernia Total or subtotal gastrectomy Intestinal Stagnant loop syndrome lleal resection Fish tapeworm ‘Chronic tropical sprue Malabsorption of cobalarnin occurs in the following conditions but the deficiency is not usually sufficiently severe to cause megaloblastic anemia Gluten-induced enteropathy ‘Cystic fibrosis and chronic pancreatitis ‘Crohn disease uncomplicated by resection or stagnant loop Drugs: slow k, phenformin, metformin, cholestyramine Table 8.2 Characeisics of red celantbodes Paroxysmal cold inavtoimmune berolicaneria (AHA) Warm AIHA Coldagalutnin disease hemoglobinuria Imeruncgibutin (96 iu W96 Themalresctviy ar a ac Fuescomplerent able Yes we Dect antigbulin st a - - 6 amc Wc a ctigeicspecticty fh ui P Steoredcel destucion taresular Extrasolar Interest Inraascuar raver Therapy Cortcasterids Avoidance of cold Ayoidanceof cod nt-C020— Wamblodfortanswion Warr boodfortersuson Spenecory CoriesteisTable 6.2 Acquired causes of folate deficiency. Nutritional Inadequate poor-quality diet Goats’ mill ‘Special diets Scurvy (Malabsorption Gluten-induced enteropathy ‘Tropical sprue Jejunal resection ‘Systemic infections Increased requirements Pregnancy, prematurity ‘Conditions with increased cell turnover Hemolytic anemias Widespread skin and other inflarn matory diseases, e.g., tuberculosis, malana Malignant diseases “Excess toss ‘Chronic dialysis. Drugs Anticonvulsants, triamterene, sulfasalazine Alcohol Liver diseasesTable 7.2. Hematologic causes of hydrops fetalis. Impaired red cell production Parvovirus 819 infection Diamond-Blackfan anemia ‘Congenital dyserythropoietic anemias ‘Congenital leukemia Increased red cell destruction Immune hemolysis: Rh and Kell Thalassemia major Pyruvate kinase deficiency Glucose phosphate isornerase deficiency ‘yB-thalassernia Rare unstable o-chain variants Blood lass Twin-to-twin transfusion syndrome Fetomatemal hemorrhageTable 8.4 Clinical and laboratory features of immune hemolysis due to Rh disease and ABO incompatibility. Rh disease ABO incompatibility (Clinical features Frequency Unusual Common Pallor Marked Minimal Jaundice Marked Minimal to moderate Hydrops ‘Common Rare Hepatosplenomegaly. Marked Minimal Laboratory features Blood type Mother Rhy ° infant Rh G+) AOrB Anemia Marked Minimal Direct Coombs test Positive Frequently negative Indirect Coombs test Positive Usually positive Hyperbilirubinemia Marked ‘Variable Red cell morphology Nucleated cells Spherocytes Table 9.8 Characteristics of the porphyria Disorder \Neurowisceral crises ‘Skin lesion ‘Age at presentation Inheritance ‘ast phys ALAD deficiency porphyia + - Anyage aR ‘Acute iteritent porphyria + - Second tothird decade aD Heed copopoph + * pith eae ” Vategateprpyra : ¢ Beloepubery ” Cutaneous porphyias Congest entropic pophys - + Before age aR Eytopseicpooparpyia - + (Chih before age a Fepatenthropiti potoprphya - + Early chdhood R Porphyria cutanea tarda - + 20-80 years VariablesTable 10.6 Proposed management strategies early intervention Penicillin Folic acid vaccination Fluids Rest Nutrition Management of acute events General measures Assessment Blood tests (full blood count, reticulocyte count, biochemistry, cultures) Chest radiography Hydration (5% dextrose or 2.5% dextrose + 0.45% saline) ‘Oxygen (if saturation <95%). Specific measures ‘Anuibiotes ‘Transfusion Simple ‘top-up’ transfusion Exchange transfusion Pain managerent Preventive strategies Central nervous system ‘Transcranial Doppler ultrasonography MR Psychornetric testing Heartiungs Echocardiography plus tricuspid jet velocity Sleep studies for nocturnal hypoxia ricneys Early meming urine forurine osmolality zones MRI Surgical intervention Nutritional High energy byes Ophthalmology reviewTable 10.5. Types of sickle events yposplenismuntection Anemia Hemolytic Aplastic Anemia of chronic disease (e.g. renal failure) Vasoocdusive Bone Abdominal ‘Splenic sequestration ‘Bowel infarction Hepatic sequestration Hepatic infarction Gallstones Chest Acute chest syndrome ‘Chronic lung disease/pulmonary hypertension Heart Eye Kidney Renal concentrating defect/enuresis Proteinuria Acute renal failure Chronic renal failure Priapism Leg ulcers Cerebral ‘Stroke Silentinfarction Neurocognitive disorders‘able 13.3 Montorng of deferoxamine tated toy. Toricty Investigations Frequency Alteration in therapy Hoh frequengy ‘Audtogran ‘eat ifpatent symptomatic, interrupt DFO immediately sancorneural Immediate reassessment Die asses body ton burden heamgios| Discontinue DFO 6 months if HC 32-7 mafa ary ver tissue Repent auctogram evry 2 mnths uni normalor=tble -AdjstDFO to HIC ee Table 152) Felina abnormalities Retnaleraminaton ——_Yeath {patent ymptomatc, —_nterupl DFO immediatly imnmdate reassessment Direct asses body ron burden \Metaphysealandspinal Radiography of wrists, Yeaty sbrermaltes knees therzco-umbar- scrapie Bone age writ Decne nhaghtvelccty Determination ofsting Tw yearly andorsiting height and standing highs ‘Decontinye FO» 6 months FHIC3.2-7 mary dy wine tise evew ewery3 months unl normal osable [AdustDFO to HIC ce Table 152) Reduce DFO to 25 mg/kg daly week Direct asee ody ton burden Discontinue DEO x 6 months if HIC <3 mg cy weight ver tse RemessHC after Gronths ‘Adjust DFO to HIC (ee Table 152) -sfor matphyscal and spnalabhormaltes equi -monthy assessment by pethatncendocrnlogst Table 14.3 A summary of the signs and symptoms of Wiskott-Aldrich syndrorre. Neonatal onset ‘Thrombocytopenia possibly exacerbated by increased platelet consumption Early childhood onset Eczema, colitis, susceptibility to pyogenic (bacterial) and opportunistic (viral, PCP) infections Lymphopenia, abnormal B-cell function with reduced IgM and elevated IgA and IgE Late childhoodiadolescent onset \Virally precipitated B-cell mmphomasTable 14.6 Clinical features of the stable phase of Chédiak—Higashi syndrome. Organ ‘Signs and symptoms skin Patchy oculocutaneous albinisen Central nervous system _Photophobia, nystagmus, ataxia Peripheral nervous systern Peripheral sensorimotor neuropathy, cranial nerve lesions Clotting Minor bleeding problems typically presenting With easy bruising and epistaxis Innate immunity Multiple life-threatening bacterial (comrronly ‘Staphylococcus aureus) and fungal infections of the mouth, skin and lungsTable 14.11 Examples of acquired neutropenias. ‘Neutropenia as the only or dominant cytopenia Infections: viral, bacterial, fungal, rickettsial and protozoal Drugs Immune Neonatal alloimmune neutropenia Primary autoimmune neutropenia of infancy and childhood Secondary autoimmune neutropenia ‘Nutrition: anorexia nervosa, copper deficiency Chronic idiopathic neutropenia ‘Neutropenia associated with complement actwation ‘Neutropenia as part of pancytopenia Acquired marrow failure due to decreased proliferation of progenitors in ‘the bone marrow, e.g., aplastic anemia, marrow infiltration Nutritional deficiency, e.g., vitamin B,, and folate deficiency Splenic sequestrationTable 14.11 Examples of acquired neutropenia. ‘Neutropenia as the only or dominant cytopenia Infections: viral, bacterial, fungal, rickettsial and protozoal Drugs ‘Immune Neonatal alloimmune neutropenia Primary autoimmune neutropeniaof infancy and childhood Secondary autoimmune neutropenia ‘Nutrition: anorexia nervosa, copper deficiency Chronic idiopathic neutropenia ‘Neutropenia associated with complement activation ‘Neutropenia as part of pancytopenia Acquired rarrow failure due to decreased proliferation of progenitors in the bone marrow, e.g, aplastic anemia, marrow infiltration Nutritional deficiency, eg, vitamin Band folate deficiency Splenic sequestration Table 15.4 Diagnostic criteria for hemophagocytic lymphohistiocytosis.* Clinical Fever Hepatosplenomegaly Laboratory Hematologic ‘Cytopenias (more than two of three lineages in peripheral blood) Hemophagocytosis Biochemical |Hypertnglyceridemia (fasting triglycerides = 2 mmol/L or = 3SD above normal) Hypofibrinogenemia (< 1.5 g/Lor< 38D below normal “Hyperferritinemia Immunologic Low or absent natural killer cell function Elevated soluble CD25 serum levels Adgitional Molecular demonstration of known gene mutation Presence of familial disease = Diagnosis requires five of the eight clinical and laboratory criteria or the Identification of specific gene mutations or presence of familial diseaseTable 14.10 Classification af congenital neutropenias. Isolated congenital neutropenias Kostrnann syndrome and severe congenital neutropenia cyclicneutropenia Neutropenia as part of congenital bane marrow failure syndromes, e.g, Fanconi anemia, dyskeratasis cangenta ‘Congenital neutropenia as part of multisystem disorder Shwachman-Diamond syndrome Barth syndrome Pearson syndrome Glycogen storage disease type Ib (SDI) ‘Congenital neutropenia in association with defects of adaptive immunity ‘Severe combined immune deficiency (SCID) and reticular dysaenesis Table 16.1 Genetic tisk factors in childhood AML. Chromosomal disorders Trisomy 21 Klinefelter syndrome Bloom syndrome Neurofibromatosis Ataxia telangiectasia Constitestionsl disorders of hematopoiesis Fanconi anemia Diamond-Blackfan syndrome ‘Shwachman—Diamond syndrome Kostmann syndrome Thrombocytopenia-absent radii syndrome Familial thrombocytopeniaTable 17.1 Clinical features at diagnosis of chronic myeloid leukemia. Common Fatigue ‘Weight loss ‘Abdominal discomfort/splenomegaly Asymptomatic (incidental finding) Uncommon Bone pain Bleeding Fever Sweating Leukostasis(e.g., priapism) Gout Table 18.4 Diagnostic criteria for myelodysplastic syndromes in children 2? At least two of the following must be present Blood cytopenia iineage dysplasia Excess of blasts (5%) in bone marrow Cytogenetic clone in bone marrow Diagnostic cnteria for JMMLS* Essential Monogytosis> 11x 10°/L Bone marrow blasts < 20% Absence of 19:22) Plus two from: White blood cell count > 10% 10°/L ‘Myeloid precursors on blood film Cytogenetic clone in bone marrow Spontaneous growth of CFU-GM in vitro "Srna Cyan NSN SSRTable 19.4 Clinical staging of HIV-related disease in children. Category Features N Asymptomatic A Mildly symptornatic. At least two of: 8 Moderately syrptornatic Single episode of a severe bacterial infection Lymphogitc interstitial pneumonitis ‘Anemia, neuiropenia, thrombocytopena Cardiomyopathy, nephropathy, hepatiti, dlarthea Candicians, severe varicella zoster or herpes simplex virus © Severely syrnptomatic ‘Two serious bacterial infections Encephalopathy (acquired microcephaly, cognitwe delay, abnormal neurology) Wasting syndrome (severe failure to thnve or downward-crossing two weight centiles) (Opportunistic infections (Pneumocystis carinii pneumonia, ytoregalovirus, toxoplasmosis, disserninated fungal infections) Disserninated mycobacterial disease Cancer (Kaposi sarcoma, lymphomas) {able 20.11 pega arm ete apr a Fare Unters Dusencticonpeerenson Laie oR ante stersemton fem oy srectpse retype tone nanow spe erp taster) <0 > eure Spanorsth ra ea ‘roger gre swan erm e20) sponses ps stent comple reson in ets apenas eresTable 23.3 Staging due to platelet count and clinical manifestation and Platelet count Management. (107) 1 Normal datly ite >20-150 Consent for observation 2 Troublesorrebleeding > 10-20 Punctual intervention to reach stage 1 3 Bleeding, Lhemogiobin <20 Intervention Table 23.7 Routine testing in addition to initial laboratory analysis in children \with persistent imrrune thrombocytopenic purpura of 3-6 months’ duration. Bone marrow analysis, endocrine function, urine analysis, abdominal ultrasound Antinuclear antibody, direct antiglobin, lupus anticoagulant, platelet antigen-specific antibodies, serum immunoglobulins with IgG subclasses, Platelet function test, coagulation studies, Viral serology (HIV, CMV, EBV, VZV, rubeola, parvovirus 819 and others) Table 23.10 Standard treatment modalities for children with immune thrombocytopenic purpura. Intravenous immunoglobulin (IVIG) Initial treatment: 0.8 g/kg once. Repeat the same dose if platelet count is <30x 10% on day 3 (72 hours after first infusion) Inemergency bleeding: 1-2 tires 0.8 g/kg, eventually together with corticosteroids and platelet transfusion Treatment in chronic ITP: 0.4 g/kg once every 2-8 weeks Corticosteroids: Prednisone 4 mg/kg daily orally or intravenously for 7 days, then tapering cover a 7-day period In emergency bleeding: methyiprednisolone 8-12 mg/kg iv. dexamethasone 0.5-1.0 mg/kgi.v. or orally, together with IVIG or platelet transfusion Ant-Rh(D) antibody SO ng/kg iv. in children with immune thrombocytopenic purpura,Table 25.1 Characteristic clinical features that differentiate primary hemostatic disorders from coagulation disorders. Table 25.3 Causes of acquired platelet function defects. ‘Drugs and other causes uremia ver disease Extracorporeal perfusion Acquired storage pool deficiency Antiplateletantibodies Acute leukemias and myelodysplastic syndromes Myeloproliferative disorders Coagulation * Inthe uncommon type 3 von Willebrand disease, the factor Vill level is low enaninh far the clinical foattires te he thse af a combined nrimary Table 26.1 Bleeding anfestatins with ahferent severities of hernaphila A and ‘Type of bleoding Severe (0.0) mits (05-409 ‘Age of ences “el yeat year eyeare Hemarthroses Spontaneous ae + - Following minor wautra pene “ Ieee harratorea pans * - Cental nenaus system ” + suigay a a 4 Dents extraction ae ae * ‘Taumra tosott se ald aH + Significant aH oe + “+44, usual +++, common; +4, not unusual +, can occurTable 262 Treatrento speci lees Desired plasma level Duration of irr factor eves in pasa alter rsatent. Type otbieed ‘after treatment ‘treatment Mejor bleed 100% nse + commence CI Seonote (CNS or bleed woking perperl nerve leopsoastetopentoneal Tenguemcdutetopharyngeal 10096 se +comtrence ct asvoinastnal reopetatve treatment Joint hernartness) 50-70% seancte Muscle Muccsal 50-70% and ranoxarc acd Minor bled 50% Dentalatraction 50% and tran aid Dental filing 308% Laceration equiong sutures 20% unt sutures remeoved Herta High thidintake + 50% Table 23.12 Treatment options in refractory imrnune thrombocytopenic purpura (see text for dosage and other details) Current treatment options Vinca alkaloids Azathioprine Cyclophospharride Cyclic high-dose corticosteroids Danazol Plasm apheresis or protein A immunoadsorption Ascorbic acd (vitamin C) ‘Splenectomy Recent treatment options Treatrrent influencing antigenerria ‘reatrrent influencing the T-cell immune response: ciclosporin, CTLA-4-1g ‘reatrnent influencing the B-cell immune response: ant-CD20 rronoclonal antibody (rituximab), ant-CD52 monoclonal antibody (Glemtuzumab),interferon-o Other options: thrombopoietin, autologous hematologic stem cll transplantation‘Type of WWD: Type 1 (-80%) Type 2 (-20%) Type 2A Type 28 Type 2M Type2N Definition and prevalence Partial quantitative deficiency of normal von willebrand factor (VWF) Qualitative defects of VWF Qualitative variants with decreased platelet- dependent function associated with the absence of high-molecular-weight multimers (Qualitative variants with increased binding affinity for platelet glycoprotein Ib Qualititative variants with decreased platelet- dependent function associated with normal VWF multimer pattern Qualitative variants with reduced binding of FV ‘Type 3 WWD (prevalence Complete absence of WWF =1 per million)Table 27.3 Clinical definitions of a significant bleeding trait. Recurrent nosebleeds requiring medical treatment (packing, cautery, desmopressin, etc.) orleading to anemia Oral cavity bleeding lasting for at least 1 hour, restarting over the next 7 days or requiring medical treatment Bleeding from skin lacerations lasting for atleast 1 hour, restarting over the next 7 days or requiring medical treatment Prolonged bleeding associated with, or following, dental extraction or other oral surgery ‘Menorrhagia requiring medical attention or leading to anemia ‘Spontaneous gastrointestinal bleeding requiring medical treatment or leading to anernia, unexplained by local causes Prolonged bleeding from other skin or mucous membrane surfaces requiring medical treatment Table 28.2 Clasifction of Ehles-Danlossynckome EDS), New Former conn Inheritance Clasp GraiseOstgeD 130000 » Ms E05 ype 130010 0 yperabity ype pero EDS pe) 130020 0 Vasa ype ‘ated echymotic EDS pe) 130060 » (25350) (asco Kyphoscoles type (russe ED typed mao a (22200 hoch type Aatrochalsauipexconpeia( EDS pes VI, 8) 130060 ” Damatcsparaitype Human dematopara (E05 ype VIC) nsat0 x Obes tors ‘elke 05 ED ype) 305200 HL Pedant type ES pe Vi) 130080 » Fbroncindelcent ED (05 tpeX! nas310 ? Farlhypembiy drone ES type) 1990 » Prop EDS ? Uspeatdfos 130070Table 28.1 Characeistisofcamiaton acasand ther doing sites, Pasma Chromosomal Moleclar No.of chains concentration Wo.of la No.of described Homostatc leas location mass(kDs) (acne) —Haife —(upiml).-——domains mutations Frevalone (referncerange) 8 0 2 46h 05, 10 0 ‘inSo0000 15-20 » 8 8 2 -t0h 10 nw tintin 15-20 Al " noon Bld 100 0 1in2rion 20-30 w 1 m2 3h 0 - » Tinton 15-25 ev rRcK-s3 18 aim 2M =H 1O 1560 tin2riion 15-20 um 2 30(Rva) 2(F) ——_10-14h(F) 010 >siMcr0D) Pa 4 wo 2 2h 5 - > tintin 15-20 Palgened) 6(Achan) «320 Tddas - > tin2mion 25 eda) Fbiog agai 0 6 Dadas 3000 - >0@pfbinogrerid tintin SOmgeL Goer) yehans) 220 ypoiernagenenia Table 308 Gusset testers. ateetcout xt) Nonbleding neonate Bedngneonate —_NATP(provenorsuspeced) a Coser rarsisninl pts Tease Tash compat pele) a8 Conor fil sabe Tease Tarshse(vth Pampa pees Considers iain ilo gands tweskefae ils, fucatng peti) Prins raja, peti, puncesteoning oboe ects) Conant cgay Furs sug) oer tason soa Cones Tease Trashse(wthtPheonpatbi pases ngprbleingge 8 ona Conotvasne ——_DonotanseTable 30.9 Inherited thrombocytopenia classified by platelet size. ‘Small platelets Wiskott-Aldrich syndrome linked thrombocytopenia ‘Normal platelets ‘Congenital amegakaryocytic throrbocytopenia ‘Aregakaryoqytic thrombocytopenia with absent radi Familial platelet disorder/acute myeloid leukaernia Thrombocytopenia with radioulnar synostosis Large platelets MYH-9 related disease Bemard-Soulier syndrome Mediterranean thrombocytopenia, Gata-1 mutation \Velocardiofacial syndrome Gray platelet syndrome Paris-Trousseau thrombocytopenia Jacobsen syndrome Table 32.11 Suggested guidelines for platelet transfusions in neonates. Platelet count < 30 » 10/1 in a neonate with neonatal alloimmune thrombocytopenia Platelet count < 30 x 10/1 with failure of platelet production Platelet count <'50 x 10°L in a stable preterm infant:* with active bleeding pprior to invasive procedure with failure of platelet production Platelet count < 100 x 10°/L in a sick preterm infant:* with active bleeding prior to invasive procedure with disseminated intravascular coagulationTable 32.6 British guidelines for RBC transfusion thresholds for infants under 4 months of age. ‘Anernia in the first 24 hours Hb 12.0 a/dL (Hct 0.36) Table 29.4 Causes of disseminated intravascular coagulation an children. Infection Malignancy, ©.g., acute leukernia 2 Trauma, e.g. head injury, bums ame = Organ destruction, e.g, acute pancreatitis _ ‘Severe immune reaction, €.g., ABO-incompatible blood transfusion Hepatic failure F Vascular abnormality, e.g,, Kasabach-Merntt syndrome Brewe gece new reacts rvanerots? ° First choice ° ° ° Second choice None ABAB A,B, AB a First choice a a a secondchoe © an AB a First choice a a B Second choice AB AB ae First choice AB Ae AB Second choice 4,8, None ‘See footnote * The choices of ABO blood groups for REC transfusion may not be appropriate for newbornsand Infants <4 months of age in whom the potential presence of maternal anti-a/s must also be considered. + In emergency situations platelets in plasma with A/B antibodies against recipient Ave antigens may be transfused. However, where possible such units should not be used unless the antl-AVB is of low titer and/or the plasma has been removed. This is especially important for infants and young children (see text). KEY POINTS: CENTRAL NERVOUS SYSTEM TUMORS v| 1, Second mast common neoplasm of childhood, after leukemia 2. Older children (>1 year): Most tumors are infratentorial (cerebellar or brainstem) ‘8. Younger children (<1 year): Most tumors are supratentorial 4, Gold standard for diagnosis: Magnetic resonance imaging with and without gadolinium enhancement 5, Back pain, extremity weakness, and/or bowel and bladder dysfunction suggestive of spinal cord lesions or metastases.KEY POINTS: ACUTE LYMPHOBLASTIC LEUKEMIA 41. Most common childhood malignancy 2, Increased risk: Patients with Down syndrome, congenital immunodeficiency syndrome, exposure to ionizing radiation; sibling of patient with acute lymphoblastic leukemia 3. Chemotherapy phases: Induction (to achieve remission), delayed intensification, maintenance 4. Survival (if in standard risk group) >80% at 6 years after completion of therapy 5. Most common sites of relapse: Bone marrow, central nervous system, testis " 1. Most common pediatric extracranial solid tumor 2. Most common malignant tumor among infants 3. Majority of children <4 years old 4, Poorer prognosis: >1 year old, metastatic disease, Myc-N amplification 5. Most metastatic at diagnosis 6. Paraneoplastic syndromes: VIP syndrome (diarrhea as a result of increased vasoactive intestinal peptide), opsoclonus-myoclonus (“dancing eyes, dancing feet”), and catecholamine excess (with flushing, sweating, headache, hypertension)Table 30.7 Classification of fetal and neonatal thrombocytopenias. Fetal Early-onset neonatal (<72 hours) Late-onset neonatal (272 hours) Alloimmune ‘Congenital Infection (e.9., CMV, Toxoplasma, rubella, HIV) Aneuploidy (e.g, trisornies 18, 13, 21 or triploidy) Autoimmune (¢.g., ITP, SLE) ‘Severe Rhesus disease ‘CongenitaVinherited (e.g., Wiskott-Aldrich syndrome) Placental insufficiency (e.g., PET, IUGR, diabetes) Perinatal asphyxia Perinatal Infection (¢.9., Escherichia coli, GBS, Haemophilus influenzae) Disseminated intravascular coagulation Alloimmune Autoimmune (¢.g., ITP, SLE) ‘Congenital infection (e.g., CMV, Toxoplasma, rubella, HIV) Thrombosis (e.9., aortic, renal vein) Bone marrow replacement (e.g., congenital Jeukernia) kasabach-Merritt syndrome Metabolic disease (e.g., propionic and methyimalonic acidernia) ‘Congenitalinherited (e.g., TAR, CAMT) Late-onset sepsis Necrotizing enterocolitis ‘Congenital infection (e.g., CMV, Toxoplasma, rubella, HIV) Autoimmune Kasabach-Merritt syndrome Metabolic disease (e.g., propionic and methylmalonic acidemia) ‘Congenitavinherited (e.g., TAR, CAMT)Trae PWS e ce) DREN TO DEVELOP LEUKEMIA Population at Risk Estimated Risk U.S. white children 1 in 2800 Siblings of a child with leukemia 1 in 700 Identical twin of a child with leukemia 1ins Children with: Down syndrome tin 75 Fanconi syndrome rin 12 Bloom syndrome ting Ataxia-telangiectasia ring Exposures: Atom bomb within 100 m 1 in 60 lonizing radiation 2 Benzene 1 in 960 see ee a Ta) UC ee wi eee eS LYMPHOBLASTIC LEUKEMIA Age: <1 year and >10 years ex Pee eps White blood cell count: +50,000/mm* Chromosomal translocation abnormalities, specifically {(8;14), t(9;22), and t(4;11) Hypoploidy (<45 chromosomes) Malignant cells, with mature B-cell or T-cell immunophenotyping Central nervous system involvement Black and Hispanic patients Males[G5 Table 20.6 Conditions associated with neonatal disseminated ata 1 intravascular coagulation. 2 3. Fetalineonatal disorders 4. Hypoxia-acidosis: birth asphyxia, respiratory distress syndrome 5. Infection 6. Meconium aspiration 7. Aspiration of arnniotic fluid a. _ Necrotizing enterocolitis 9. Brain injury 0. Hypothermia Hernolysis aE SSEMIA 1. Normal hemoglobin (HbA): Tetramer of two 2 and two B chains lis, or sepsis 10. 2. Associated with quantitative reduction in globin synthesis 3. Homozygous #-thalassemia is most severe form with pallor, jaundice, hepatosplenomegaly, growth retardation 4. Expansion of facial bones resulting from extramedullary hematopoiesis 5. Severity of a-thalassemia depends on number of genes deleted (1 to 4) STAINS. c-Thalassemia: More common among people of Southeast Asian ethnicity 7. P-Thalassemia: More common in people of Mediterranean ethnicity ary Tumors Secondary Tumors EC ae Se Hodt1. The introduction of whole cow milk before the age of 1 year increases risk as a result 0 occult gastrointestinal bleeding. 2. Red blood cell distribution width is increased because deficiency results in uneven red blood cell size (anisocytosis). 3. Low levels of ferritin indicate diminished tissue iron stores. Acut M4. This condition impairs cognitive development in infants. Sare5. Absence of anemia does not exclude the possibilty of iron deficiency. tron depletion is, relatively advanced before anemia develons.UT MWC LL a meh oe hse PC TU eee CULE Factor V Factor Vil. Factor Vill Liver disease Low Low Normal or increased Vitamin K deficiency Normal Low Normal Disseminated intravascular coagulation Low Low Low KEY POINTS: SICKLE CELL DISEASE git 1. A genetic Bara 2. Eight perce) 3. Crises inclu Test Usual Results 4 Tae fk {0% Prothrombin time; activated partial thromboplastin time Prolonged Fibrinogen <100 mg/dl" 8. Pactvilts (F piatelet count Low o-Dimer >2 no/mL Factors Il, V, and VIII Usually low* Lia Se Hemophilia A: Factor VIII abnormalities (75% to 85% of total cases) Family history is not always positive; up to one third of cases of factor VIII deficiency are caused by a spontaneous mutation. Hemophilia B: Factor IX abnormalities ae Severity based on factor levels: Severe (<1%), moderate (1% to 5%), mild (5% to 25%) o Common initial presentation: Bleeding after circumcisionTS aaa laa aa an Se eS 1. Failure to thrive Medust 4 > persistent cough Iyeatiiaia ¢ 3 Persistent candidiasis 4, Absolute lymphocyte count <2000/mm® Mycoses; lat vata ia ‘aro in 8D, pel Cyptspium, Premays ca pegs Camylcbacter,enterovinses Cll nigs Reet expiry tat Pour rth and eo hive; Pou wound ing in Raid iets dame val candids sin rates; dias, borers; rhs iis cals; pase oprnihc demas ngelgn css ange hogs ath inet gafersis test elt wiht pus; incase dermatosis, ies; toy trons, ——_sugurte aes suscepti eigencehls beptlemnegy pedis; absass; ——_inton Cr dase steams, blader outlet obstructionPUTAS aes CUS Type | Type llA Type IIB Type IIN Frequency 65-80% = 10%-12% SoHo NoHo Genetic Autosomal Autosomal Autosomal Autosomal transmission dominant =— dominant dominant dominant Ristocetin Low Low Low Normal cofactor activity Low-dose Normal Normal Increased Normal ristocetin- induced platelet aggregation Multimeric Normal mix Large, Large multimers — Muttimers Clectrophoretic (various intermediate »——_absent normal pattern sizes) forms absent Response to Good Poor Decreases Raises low desmopressin platelets factor VIIanh COMMON CAUSES OF PROLONGED PROTHROMBIN TIME (PT) Oa aS Scenario Common and Important Causes Comments Prolonged PT Prolonged aPTT Prolonged PT and aPTT Vitamin K deficiency Liver disease Warfarin Factor VII deficiency Disseminated intravascular coagulation (DIC) Von Willebrand disease Hemophilia (factor VIII, IX, or XI deficiency) Heparin Antiphospholipid antibodies (associated with minor infections or, rarely, autoimmune or thromboembolic disease) Heparin Warfarin Liver disease DIC Isolated PT elevation is sensitiv marker early in DIC development Rare deficiencies of factor XII, congenital abnormalities of the receptor for vitamin Byo- intrinsic factor complex Gastric mucosal defects that interfere with the secretion o intrinsic factor or phosphokinase may also elevate aPTT but are not Clinically significant Half of children with prolonged aPTT do not have a bleeding disorder Fibrinogen measurement can help distinguish among liver disease and DIC (decrease in fibrinogen) and vitamin K (no decrease in fibrinogen)