Pediatric Board Review Course Pediatric Hematology/Oncology Kusum Viswanathan, MD Vice Chair, Dept of Pediatrics Director, Divn of Pediatric Hematology/Oncology

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<ul><li>Slide 1</li></ul><p>Pediatric Board Review Course Pediatric Hematology/Oncology Kusum Viswanathan, MD Vice Chair, Dept of Pediatrics Director, Divn of Pediatric Hematology/Oncology Brookdale Univ Hospital and Medical Center Slide 2 Case 1 6 week old term infant referred for anemia. No Sx Hb 7.5, Retic 2 %, Bili 3.5, Direct 0.5. Mother O+, Baby A -, Direct Coombs + Mother O+, Baby A -, Direct Coombs + Cord blood Hb 14.2 g/dL. Bilirubin 15mg/dL at 48 hours of life, recd photo Rx and d/c at 5 days. Cord blood Hb 14.2 g/dL. Bilirubin 15mg/dL at 48 hours of life, recd photo Rx and d/c at 5 days. Slide 3 Most likely explanation for the anemia is 1. G 6 PD deficiency 2. Hereditary spherocytosis 3. Physiologic anemia 4. ABO incompatibilty 5. Rh hemolytic disease Slide 4 Newborn -anemia Hemoglobin at birth is 17 g/dl, MCV over 100. Falls to 11-12 by 6 weeks of age- nadir. Erythropoietin production shifts from liver to kidneys and reduces because of increase in PaO2. Anemia at birth could be : hemoglobin not have equilibrated- repeat Hemorrhage, may not have had time to mount a retic response Acute hemorrhage- pallor and tachypnea Look at MCV- low MCV-suggestive of chronic feto-maternal hemorrhage Alpha Thalassemia trait. Alpha Thalassemia trait. Kleihauer-Betke- Hb F resistance to acid elution Slide 5 Newborn-Thrombocytopenia A newborn has a completely normal physical exam except for a few petechiae. Platelet 50,000. Differential diagnosis: Production defects: TAR, Megakaryocytic hypoplasia, Trisomy 13, 18. Wiskott-Aldrich (small plt, X-linked, eczema, SCT cure) Infections- viral, bacterial, Infiltration (Gauchers, Niemann Pick, Leukemia) Destruction: Allo-immune (iso-immune)- Platelet group incompatibilty Auto-immune: Mat ITP, Drugs (thiazide, tolbutamide), SLE Infections: CMV, Rubella, herpes, DIC Loss: Kasabach- Merritt syndrome (hemangiomas, DIC- Rx DIC and hemangioma with Steroids, interferon, VCR) Slide 6 The treatment of choice for alloimune neonatal thrombocytopenia is: 1. random platelet transfusion 2. IVIG 3. Steroids 4. Exchange transfusion 5. Washed maternal platelets Slide 7 Immune thrombocytopenia Auto-immune: Pregnant women with ITP/Hx of ITP Passive transfer of antibodies (IgG) from mother. Even when mother has a normal platelet count (Splenectomy) Nadir-few days; Platelets &lt; 50,00 have 1% risk of ICH. IVIG to mother, Fetal platelet counts, C sec, US, IVGG to baby Allo or Iso-Immune: Normal platelet count in mother Similar to Rh disease; PL A1 antigen/ Zw a negative mother. 97% of population is PL A 1 positive Sensitization early in pregnancy Plt function defect because Anti-PL A1 interferes w/aggregation. Severe bleeding more likely; first born affected; Recovery in 2-3 weeks Mothers washed (PLA1 neg) platelets; IVIG; Ultrasound; Steroids Slide 8 Kasabach- Merritt, TAR Slide 9 15 months old girl presented in ER with h/o URI, and scattered petechiae and ecchymoses over the body and lower extremities. Physical exam normal, no hepatosplenomegaly. WBC-6,000, Hb 12.8, Plts-5,000, Diff: Normal Smear- The next step is to 1.perform a bone marrow aspirate to confirm the diagnosis 2.Do a skeletal survey to rule out bony fractures 3.Start treatment with either IVIG or anti-D 4.Administer platelet transfusion Slide 10 ITP Usually acute onset; immune mediated; post viral Peak 2-5 years of age, males=females Spontaneous bruises, petechiae PE no lymphadenopathy (LN), hepatosplenomegaly. CBC- other cell lines normal, large plts on smear Treat if plt&lt; 10,000 or wet ITP, avoid NSAIDS, Aspirin Treat- IVIG best response, 48-72 hours; Side effects. Anti-D (WInRho) Rh+,hemolysis, quick response Steroids good response, SE, inexpensive, need BM BM- Increased megakaryocytes, otherwise normal Slide 11 Petechiae, HSP Slide 12 Petechiae ITP- Thrombocytopenia Hemolytic Uremic Syndrome Low plt ct, Hemolysis, high LDH, sick patient, Uremia, microangiopathic hemolysis on smear. Henoch-Schonlein Purpura Purpuric lesions on lower extremities and buttocks Abdominal pain, arthritis. IgA deposition, normal plt ct. ALL Low plt ct, lymphadenopathy (LN), hepatosplenomegaly, other cell lines affected Drug induced- Likely By reducing production or increasing destruction DIC Slide 13 Platelet Size Normal platelet 7-10 days Large platelets: ITP May Hegglin (Dohle bodies in neutrophils, Plt function normal). Bernard Soulier syndrome (AR, Plat function disorder). Small platelets: Wiskott Aldrich syndrome ( X-linked, recurrent infections, eczematoid rash, platelet dysfunction) Slide 14 A 2 year old boy presents for evaluation of a chronic pruritic eruption. His medical history is remarkable for recurrent epistaxis, otitis media, and pneumonia. Physical examination reveals erythematous, slightly scaling patches on the trunk and in the antecubital and popliteal fossae. Petechiae are present profusely. This is most suggestive of 1.Acrodermatitis enteropathica 2.Ataxia telangiectasia 3.Atopic dermatitis 4.Langerhans cell histiocytosis 5.Wiskott-Aldrich syndrome 6 Slide 15 Platelet function defects Normal platelet number Glanzmann thrombasthenia AR, Abnormal aggregation Bleeding disorder, check h/o consanguinity Hermansky Pudlak Syndrome: AR, Decreased dense granules In Puerto Ricans Oculocutaneous albinism Slide 16 Thrombocytosis H - Hemorrhage, Hereditary Asplenia, Down myeloprol. I- Infections, Kawasaki, Immune: GVH, Nephrotic syndrome P- Polycythemia vera, Myeloproliferative, Essential L- Leukemia (CML) A- Anemia,- Iron, Vit E, Sideroblastic T-Tumors E- Epinephrine, Steroids L-Lymphoma, Hodgkins E- Exercise, T-Trauma, Fractures S-Splenectomy Slide 17 Anemia An 18 month old girl brought in for pallor. Normal diet and PMH. She is alert, interactive, only pallor, normal vital signs, No hepatosplenomegaly, lymph nodes or bruises. CBC- Normal WBC, Plt, Hb 4.5g/dl, MCV 74, Anemia Reduced production Increased destruction Loss What else do you want?? Slide 18 Reticulocyte count Normal/Low- reduced production Iron deficiency anemia- MCV will be low ALL (leukemia)- other findings, LN, HSM Diamond Blackfan anemia- Us &lt; 1 year of age; facial/thumb abn, Cong heart dis, MCV Incr, rbc ADA increased, responds to steroids, BMT curative. TEC: Over 1 year of age, Pallor, transient rbc production failure, recovers, MCV and Hb F high during recovery, rbc transfusion, rbc ADA normal. Slide 19 Aplastic Anemia Congenital - Fanconi anemia, Dyskeratosis congenita, Shwachman- Diamond syndrome, Amegakaryocytic thrombocytopenia Fanconis anemia-AR, s hromosomal Fanconis anemia-AR, short stature, microcephaly, microphthalmia, epicanthal folds, Caf au lait, dangling thumbs, congenital dislocated hips. Chromosomal breakage increased by diepoxybutane (DEB) or mitomycin C. Hemorrhages, infections, leukemia, myelodysplastic syndrome, liver tumors,Acquired Infection- hepatitis, EBV,CMV, parvovirus B19, HIV Drug induced- Chloramphenicol Exposure to Toxins, Radiation Autoimmune disease such as lupus Idiopathic Treatment- BM/Stem cell transplant Slide 20 Normal smear Slide 21 Microcytic anemia is a characteristic laboratory abnormality of all listed diseases except 1. Iron deficiency 2. Lead poisoning 3. Sickle cell disease 4. Thalassemia trait Slide 22 Microcytic anemia Slide 23 Iron deficiency Low MCV, low MCHC, low retic, RDW normal initially, will increase after treatment, Low Iron, Incr TIBC, Transferrin low, Ferritin low Causes: Inadequate dietary intake Toddlers, too much milk, less solids, Breast fed need iron supplements poor absorption Blood loss: Menstrual, GI tract, Meckels, Epistaxis D/D: Thalassemia trait- MCV much lower in prop to anemia, Anemia of chronic disease- low Fe, low TIBC, normal /high Ferritin. Slide 24 Beta Thalassemia Minor Quantitative defect in globin chains Reduced production of Beta chains Hb electrophoresis Hb A- 2 Alpha, 2 Beta Hb F- 2 Alpha, 2 Gamma Hb A2- 2 Alpha, 2 Delta Excess Alpha combines with Gamma or Delta- Increased Hb F and A 2. Smear abnormalities significant even with MILD anemia. Anemia Low MCV, normal RDW, normal retic Smear shows aniso and poikulocytosis, target cells, microcytes, misshapen cells, basophilic stippling Hb Electrophoresis: Increased Hb A 2 and/or F. Normal iron studies, no response to iron Slide 25 Beta Thalassemia Major No production of Beta chains Autosomal recessive 25 % chance with each pregnancy Pre-natal testing for carriers Chorionic villous sampling for diagnosis Transfusion dependent-allows for normal development Pen Prophylaxis, Anti oxidants Splenectomy after age 5 Iron overload- inherent and transfusion Need chelators Slide 26 Thalassemia- Alpha Reduced Alpha chains 4 types- carried on 4 allelles. (xx/xx) One absent- Silent carrier (x-/xx) 2 absent- Alpha Thal trait (xx/- - or x-/x-) 3 absent- Hb H disease (x-/- -) Has 4 excess Beta chains) 4 absent- Hydrops fetalis (- -/- -) NB period: Excess Gamma chains form Hb Barts- FAST moving Hb on Newborn screening Slide 27 Megaloblastic anemias Vitamin B 12 or Folate deficiency (defective DNA synthesis) Defective maturation of other cell lines- leukopenia and/or Thrombocytopenia Hypersegmented neutrophils, large metamyelocytes and bands Causes hyperhomocysteinemia. Dietary deficiency of vitamin B12 due to vegetarianism. Can occur in breast-fed infants of vitamin B12deficient mothers Severe vitamin B12 deficiency - a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression Underlying mechanisms delayed myelination or demyelination of nerves alteration in the S-adenosylmethionine:S-adenosylhomocysteine ratio imbalance of neurotrophic and neurotoxic cytokines accumulation of lactate in brain cells Elevated methylmalonic acid and/or total homocysteine are sensitive indicators of vitamin B12deficient diets Slide 28 Case 3 year old patient is brought to the ER with complaints of feeling very tired over the past 3 days. Patient is pale, jaundiced with the spleen tip palpable. CBC Hb 5, Retic 5 %, LDH Increased, What does this sound like?? Slide 29 Reticulocyte count- Increased Hemolysis Intrinsic- Membrane defects-Hereditary spherocytosis (HS) Enzyme-G 6 PD deficiency Hemoglobinopathies Extrinsic- AIHA (Auto-immune hemolytic anemia), DIC, IV hemolysis Loss Blood loss Slide 30 Question A previously well African-American child visited Africa and was given malarial prophylaxis. He experienced pallor, fatigue, and dark urine. His hemoglobin level decreased from 14.8 to 9 g/dL. SMEAR Slide 31 An African-American child visited Africa and was given malarial prophylaxis. He experienced pallor, fatigue, and dark urine. His hemoglobin level decreased from 14.8 to 9 g/dL. The most likely diagnosis is 1.Hereditary spherocytosis 2.Sickle cell disease 3.Hepatitis 4.G6PD deficiency 6 Slide 32 Hemolytic anemia History; Recent infection, drug exposure, illness, dark urine, anorexia, fatigue, pallor Family h/o gallstones, splenectomy Physical Examination: Pallor, tachycardia, tachypnea, splenomegaly. Peripheral smear: Blisters, spherocytes Slide 33 Children with congenital spherocytosis have all of the listed conditions except: 1. positive Direct Coombs 2. splenomegaly, gallbladder stones 3. abnormalities in spectrin and /or ankyrin 4. increased MCHC 5. abnormal osmotic fragility test. 6 Slide 34 Spherocytes Spherocytes Nucleated rbc Coombs-AIHA Osmotic fragility-HS Slide 35 HS- with severe anemia A 6 year old girl who has hereditary spherocytosis presents with a 1 week history of fever. Physical examination and history reveal abdominal pain, vomiting, fatigue and pallor. Her hemoglobin is typically about 10 g/dL with a reticulocyte count of 9%, but now, her hemoglobin is 4 g/dL and the reticulocyte count is 1%. Her bilirubin is 1 mg/dL. Of the following, the MOST likely cause for this girls present illness is infection with Coxsackie virus Parvovirus B19 Epstein-Barr virus Hepatitis A virus Influenza A virus Slide 36 HS- with severe anemia 1.Coxsackie virus 2.Parvovirus B19 3.Epstein-Barr virus 4.Hepatitis A virus 5.Influenza A virus 6 Slide 37 Newborn Screening You get a call from a frantic parent because she received a letter from the State regarding her babys test results on NBS. FS- SS disease, S-B 0 Thal, Sickle cell w/ HPFH. FSA- Sickle B + thal, Sickle cell trait FSC- SC disease FAS- Sickle cell trait FAC- Hb C trait FAE- Hb E trait FE- Hb EE disease, E-Thal Slide 38 Sickle cell Hemolysis- life span 20-50 days. Abnormal cell shape, abnormal adherence to endothelium, decreased oxygenation, Increased polymerization. Symptoms start by 2-4 months of age. Hb electrophoresis, S &gt;75 %. Start Penicillin daily and give until age 5. Prevention of pneumococcal infections. PPV (Pnu-23) age 2, 5 Meningococcal vaccine Folic acid daily Slide 39 The mother of a 10 month old baby with SS disease asks you about prognostic indicators. All of the following indicate likelihood of more severe disease except: 1. High WBC 2. Associated alpha thalassemia trait 3. Low hemoglobin 4. Repeated episodes of dactylitis Slide 40 Sickle cell crises Vaso-occlusive crisis- dactylitis, long bones, back, chest. Trt. Pain meds, hydration. Aplastic crisis: low Hb, low retic, Secondary to Parvovirus infection. Splenic sequestration crisis: spleen palpation Hyperhemolytic crisis Slide 41 Sickle cell Acute Chest Syndrome New infiltrate on X-ray, fever, chest pain, back pain, hypoxia. Due to infarction, infection, BM fat embolism Treat: Antibiotics to cover pneumococcus, Mycoplasma, Chlamydia, Bronchodilator, Oxygen, Incentive spirometry, transfusion, Steroids (controversial). Avoid overhydration Slide 42 Pulmonary Hypertension Prevalence of pulmonary HT in SCD from 20-40 %. The presence of hemolysis, chronic anemia, and the need for frequent transfusions were directly associated with development of PHT. On follow-up, PHT was significantly associated with an increased risk of death. -Am J Hematol July 2004 -N Engl J Med Feb 2004. Slide 43 TCD- Transcranial Doppler A routine TCD on a 4 year old patient with SS disease shows a Cerebral blood flow (CBF) of 210 cm/second. What is the next step? STOP studies- STOP I and II Slide 44 According to the STOP protocols, all children with abnormal TCD require enrollment in hypertransfusion protocol till (choose one) 1. Repeat TCD is normal 2. Continue indefinitely 3. the child reaches 18 years 4. MRA/MRI are reported normal 6 Slide 45 Sickle cell and Stroke Affects 10 % of patients Infarctive stroke (younger patients) and Hemorrhagic stroke (older) STOP I study established the role of yearly TCD (transcranial doppler) to measure cerebral blood flow velocity as a tool for determining stroke risk. Transfusion therapy as current therapy for high risk patients (CBF&gt; 200cm/sec) Reversal of CBF velocity is not sufficient to stop transfusion therapy. (STOP II) Slide 46 Sickle cell and Transfusions Transfusion indications: Acute anemia (Aplastic, Hyperhemolytic, Sequestration) Hypoxia (A...</p>

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