Pediatric Board Review Course Pediatric Hematology/Oncology

1. Pediatric Board Review CoursePediatric Hematology/Oncology KusumViswanathan, MD Chair, Department of Pediatrics Director, Division of Pediatric Hematology/Oncology Brookdale University Hospital and Medical Center

2. A newborn baby has a hemoglobin of 14 gm/dL and the MCV is 82 .True statements regarding a newborn baby include all of the following except: 1. This is a normal Hb and MCV for a newborn 2. Feto-maternal hemorrhage can be a cause of anemia 3. A low MCV is suggestive of chronic feto-maternal hemorrhage or Alpha Thalassemia trait. 4. Kleihauer-Betke test looks for the presence of fetal hemoglobin in the mother’s blood 5. The Apt test looks for the presence of adult hemoglobin in the baby’s gastric aspirate

3. 6 week old • 6 week old term infant referred for anemia. Hb 7.5, Retic 2 %. Mother O+, Baby A -, Direct Coombs + Cord blood Hb 14.2 g/dL. Jaundice of 15mg/dL at 48 hours of life, recd photo Rx and discharged at 5 days. No complaints, pale, Bili 3.5, Direct 0.5. • Blood smear shows spherocytes

4. Most likely explanation for the anemia • G 6 PD deficiency • Hereditary spherocytosis • Physiologic anemia • ABO incompatibilty • Rh hemolytic disease

5. ARS Question 1-The treatment of choice for alloimune neonatal thrombocytopenia is • random platelet transfusion • IVIG • Steroids • Exchange transfusion • Washed maternal platelets

6. Auto-immune Thrombocytopenia • True statements regarding Newborn Auto-immune Thrombocytopenia include all except: • Occurs in babies born to mothers with ITP/Hx of ITP • It is because of passive transfer of antibodies (IgM) from mother. • The mother can have a normal or low platelet count • The nadir occurs a few days after birth • Platelets < 50,00 have a 1% risk of ICH Treatment: IVIG to mother, Fetal platelet counts, C sec, US, IVGG to baby

7. Allo-Immune Thrombocytopenia • 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 A1 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 • Mother’s washed (PLA1 neg) platelets; IVIG; Ultrasound; Steroids

8. Kasabach- Merritt, TAR

9. 15 month old female presented to the ER with h/o URI, and scattered petechiae and ecchymoses over the body and lower extremities. • Physical exam normal, no hepatosplenomegaly. WBC-7,000, Hb 12.8 gm/dl, Plts-5,000, Normal differential- Next step • perform a bone marrow aspirate to confirm the diagnosis • Non-accidental injury; skeletal survey to rule out bony fractures • treatment with either IVIG or anti-D • Administer platelet transfusion

10. Acute ITP • Usually acute onset; immune mediated; post viral • Peak 2-5 years of age, • PE –no lymphadenopathy (LN), hepatosplenomegaly. • CBC- other cell lines normal, large plts on smear • Treat if plt< 10,000 or wet ITP, • Treat- IVIG best response, 48-72 hours; blocks Fc receptors,SE • Anti-D (WInRho)- Rh+ ,hemolysis, quick response • Steroids good response, block phagocytosis, reduces antibodies, SE, inexpensive, need BM • BM- Increased megakaryocytes, otherwise normal • Chronic- If >6 months, F>M, older, unpredictable prognosis

11. ARS Question-212 year old male was seen in ER with complaints of joint pain, swelling of the feet, abdominal pain and rash. Physical examination revealed a maculo- papular rash with ecchymosis and petechiae over extremities and buttocks. CBC showed WBC-8, Hgb-12.3 gr/dl, Plts-324. Normal Differential. PT-11.0s/PTT-30s. Next step in evaluating this patient is: • Checking stools for occult blood • Obtaining consent for BM aspirate • Urgent Hem/Onc consult • Barium enema

12. Petechiae, HSP

13. A 2 year old boy presents for evaluation of a chronic pruritic eruption. H/o recurrent epistaxis, otitis media, and pneumonia P/E reveals erythematous, slightly scaling patches on the trunk and in the antecubital and popliteal fossae. Petechiae too- most suggestive of • Acrodermatitisenteropathica • Ataxia telangiectasia • Atopic dermatitis • Langerhans cell histiocytosis • Wiskott-Aldrich syndrome

14. 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) Large platelets

15. ARS-3--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 76, Reticulocyte count 0.3%. You are considering TEC-Transient Erythroblastopenia of childhood. All are true except: • Patients are often over a year of age • 60 % recover • MCV and Hb F are high during recovery • Treat with red cell transfusions • The rbc ADA is normal

16. Normal smear

17. An 8 month old girl with a history of ventricular septal defect and horseshoe kidney presents for a health maintenance visit. Her parents are concerned that she is not feeding well, appearing to become “tired” soon after beginning to breastfeed. She is tachycardic and appears pale. Her hemoglobin level is 3.8 g/dL. Peripheral smear reveals macrocytic red blood cells. The bone marrow aspirate shows normal cellularity of the marrow with markedly decreased erythroid precursors. • Which of the following findings is most likely to be identified during additional physical examination of this patient? • Multiple superficial hemangiomas • Cutis aplasia • Bifid thumbs • Speckled white rings in the periphery of the iris • Posterior parietal hair whorl

18. Microcytic anemia is a characteristic laboratory abnormality of all listed diseases except • Iron deficiency • Lead poisoning • Sickle cell disease • Thalassemia trait

19. Microcytic anemia

20. Anemia A blood smear taken from a toddler shows microcytic hypochromic anemia. Iron supplementation therapy is started. When will the reticulocyte response be at maximum? • 1-2 days • 5-7 days • 14-21 days • 3-4 weeks • about 6 weeks

21. Iron deficiency questions • Low MCV, low MCHC, low retic, RDW can be normal, Low Iron, Incr TIBC, Transferrin low, Ferritin low • Causes: Inadequate dietary intake • Toddlers, too much milk, less solids, Breast fed need iron supplements • 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.

22. ARS Question-4- 3 year old comes for a routine check and found to be anemic. P/E Normal. CBC Hb 8.9, MCV 58, Iron levels are normal. Hemoglobin electrophoresis is done and shows Beta Thalassemia trait. All are true except: • The MCV is always low • Fetal hemoglobin is often > 2% • Hemoglobin A 2 is often > 3.5% • May respond to Iron • RDW is usually normal

23. 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 A2. 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 A2 and/or F. Normal iron studies, no response to iron Beta Thalassemia Minor

24. Beta Thalassemia Major • No production of Beta chains- Chromosome 11 • 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 • BMT is a cure

25. ARS- Q- 5-4 year old male with no complaints. Routine CBC showed a Hb 10gm/dL, MCV 62, RDW 12.5 , Retic 0.2%, Normal Iron studies, Hemoglobin electrophoresis was normal with normal Hb A2 and Hb F. What is the most likely diagnosis? • Hookworm infestation • Thallassemia • Thallassemia • Hereditary spherocytosis • GI bleeding

26. Regarding Alpha Thalassemia All of the statements are true except: • It is carried on 4 alleles • The severe form is Hydropsfetalis • Hemoglobin H disease occurs when 3 alleles are affected • Diagnosed by newborn screening when a “fast moving” hemoglobin is noted. • Fast moving hemoglobin on newborn screening is made up of a hemoglobin with 4 beta chains

27. 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

28. Peripheral Smear • 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. • Hereditary spherocytosis • Sickle cell disease • Hepatitis • G6PD deficiency

29. Children with hereditary spherocytosis have all of the listed conditions except • positive Direct Coombs • splenomegaly, gallbladder stones • abnormalities in spectrin and /or ankyrin • increased MCHC • abnormal osmotic fragility test.

30. A 6 year old girl who has hereditary spherocytosis presents with a 1 week history of fever. • Physical exam reveals abdominal pain, vomiting, fatigue and pallor. Her hemoglobin is typically about 10 g/dL with a retic count of 9%, but now, her hb is 4 g/dL and the retic count is 1%. The bilirubin is 1 mg/dL. Of the following, the MOST likely cause for this girl’s present illness is infection with • Coxsackie virus • Parvovirus B19 • Epstein-Barr virus • Hepatitis A virus • Influenza A virus

31. A six-year-old previously-well boy presents following a viral infection with a 3-day history of increasing pallor and jaundice. • Hemoglobin is 6.2 gm/dl. The peripheral blood smear is shown here. Which of the following lab studies would be most helpful in determining the correct diagnosis right away? • Osmotic fragility test • G6PD assay • Heinz body prep • Direct antiglobulin test • Serum haptoglobin level

32. A six year-old previously-well girl presents with a three day history of diarrhea and increasing pallor • Hbis 6.2 gm/dl, Plt 40,000. The peripheral blood smear is shown here. Which of the following tests would be most helpful in determining the correct diagnosis? • Serum LDH • Bone Marrow aspirate • Direct antiglobulin test • G6PD screening test • Serum creatinine

33. ARS- Question 6-Newborn screening of one of your new clinic patient is reported as follows; Hb A- present, Hb F-present, Sickle hemoglobin- present. Repeat confirmed this. You will explain to the mother that her child has: • Sickle cell disease • Normal pattern for Afro-Americans • Thalassemia trait • Sickle cell trait.

34. Question Your state neonatal screening program reports that an infant in your practice has a pattern of hemoglobin F and S on newborn screening. The underlying disorder that would most likely present with this pattern is: • Congenital hemolytic anemia. • Sickle cell anemia and sickle beta+thalassemia. • Sickle cell anemia and sickle beta0 thalassemia. • Sickle cell anemia (hemoglobin S-C disease). • Sickle cell trait.

35. Newborn Screening Questions • You get a call from a frantic parent because she received a letter from the State regarding her baby’s test results on NBS. • FS- SS disease, S-B0Thal, 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

36. Life span 20 days Abnormal cell shape abnormal adherence to endothelium Symptoms start by 2-4 months of age. Hb electrophoresis, Hb S has to be over 60% Penicillin daily until age 10. Prevention of pneumococcal infections- asplenic. PPV (Pnu-23) age 2, 5 Meningococcal vaccine early two doses and every 5 years. Folic acid daily Sickle cell – which 2 are wrong

37. Sickle cell questions • Vaso-occlusive crisis New infant born in another country presenting with swollen hands---Dactylitis • Aplastic crisis: • low Hb, low retic, Secondary to Parvovirus B 19 infection. • Splenic sequestration crisis: • Sudden enlargement of the spleen in SS or older SC patient • Rx- Transfuse • Teach spleen palpation • Splenectomy

38. Transfusions in Sickle cell • All of these have been indications for transfusion in Sickle cell disease except: • Acute drop of hemoglobin • Aplastic crises • Acute Chest Syndrome • Leg ulcers • Stroke

39. ARS- Question 7- 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: • High WBC • Associated alpha thalassemia trait • Low hemoglobin • Repeated episodes of dactylitis

40. True statements regarding Acute Chest Syndrome include all except 1. Presents with a new infiltrate on X-ray 2. Due to infarction, infection, BM fat embolism 3. Treat with antibiotics to cover pneumococcus, Mycoplasma, Chlamydia 4. Treat with bronchodilator, Incentive spirometry, transfusion 5. Intensive hydration is important

41. 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 TCD- Transcranial Doppler

42. ARS-Question 8-According to the STOP protocol all children with abnormal TCD require enrollment in hypertransfusion protocol till (choose one) • Repeat TCD is normal • Continue indefinitely • the child reaches 18 years • MRA/MRI are reported normal

43. True statements about Sickle cell and Hydroxyurea are all except • FDA approved for children • Increases hemoglobin F level • Increases hemoglobin • Decreases WBC – ancillary effect • Reduces number of ACS, VOC

44. A healthy 5 year old boy- 2 day hx of fever, P/E normal No hepatosplenomegaly, LN, no focus of infection. CBC WBC 3, Neutrophils 25 %, Hb 12, Platelet 200X109/L, ANC 750. Most appropriate step is • Amoxicillin for 10 days • G- CSF for 10 days. • BM aspirate • Refer to a hematologist • Repeat CBC in 1-2 weeks

45. Neutropenia • A 2-year-old boy has had several 10-day-long episodes of fever, mouth ulcerations, stomatitis, and pharyngitis. These episodes have occurred at about monthly intervals. Absolute neutrophil counts (ANC) have been 50/mm³on day 1 of each illness, 500/mm³ on day 10, and 1,500/mm³ on day 14. • Among the following, the MOST likely cause for the findings in this patient is • chronic benign neutropenia • cyclic neutropenia • Schwachman-Diamond syndrome • severe congenital neutropenia • transient viral bone marrow suppression

46. PT, PTT If the PTT is prolonged, you can do a mixing study. Mix patient plasma with equal amount of normal plasma and repeat the test. All of the following are true except • If the PTT corrects after a mixing study, indicates that it is because of a deficiency in factor. • If the PTT does not correct after a mixing study, indicates that it is because of a circulating anti-coagulant • If the PTT corrects, then do a Factor VII assay • If the PTT corrects, do a Factor VIII, IX, XI assay

47. A healthy 2-day-old boy born at term undergoes circumcision. Bleeding noted at the site 10 hours after the procedure and increased steadily over the past 4 hours. Findings on exam are unremarkable except for bleeding along 2 to 3 mm of the surgical site; no petechiae or purpura. • Disseminated intravascular coagulation • Factor VIII deficiency hemophilia • Immune thrombocytopenic purpura • Neonatal alloimmune thrombocytopenia • Von Willebrand disease

48. Hemophilia All are true for Hemophilia except • One unit/kg of Factor VIII increases the level to 2%. • The half life of Factor VIII is 12 hours • Inheritance is X-linked recessive • Severe Hemophiliacs have a Factor level of 10 % • 30% develop inhibitors

49. Hemophilia Questions • Factor VIII deficiency (Hemophilia A)-85% • X-linked recessive, Carriers asymptomatic • Severe<1%, Moderate 1-5, Mild 6-30 % • Treat Recombinant Factor VIII 1unit/kg raises factor level by 2 %. Half life 12 hrs. Joint bleeds need100%, muscle bleeds 50 %. • DDAVP for mild cases. • 30 % develop inhibitors after infusions with concentrate (Approx 50 infusions) • Factor IX deficiency (Hemophilia B) • X-linked recessive, less common

50. A patient with Hemophilia A has asked you about the possibility of his children being affected with the disease. His partner is normal • There is a 50 % chance that his sons will have the disease. • There is a 50 % chance that his daughters will be carriers • There is a 100 % chance that his sons will have the disease • There is a 100 % chance that his daughters will be carriers