PowerPoint Presentationnysaap.org/blog/2018HemOnc.pdf · 8. Coagulation disorders 9....

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Pediatric Hematology- Oncology

Board Review

Richard Drachtman, M.D.

Professor of Pediatrics and Clinical Section Chief –Pediatric Hematology-Oncology

Rutgers Cancer Institute of New Jersey

Rutgers Wood Johnson Medical School

Exam Weights (ie, the percentage of test questions that fall within each content domain)for all three General Pediatrics examinations (initial certification, maintenance ofcertification, and in-training

• Domain 9: Oncology (2%)

• A. Clinical presentation

• B. Malignancies• 1. Hematologic/lymphatic• 2. Central and peripheral nervous systems• 3. Ocular• 4. Renal• 5. Reproductive• 6. Musculoskeletal/dermal

• C. Other Aspects• 1. Complications of cancer treatment• 2. Oncologic emergencies• 3. Pain and palliative care

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Domain 10: Hematology (4%)A. Clinical presentationB. Diseases, disorders, and conditions

1. Quantitative erythrocyte disorders2. Qualitative erythrocyte disorders3. Quantitative leukocyte disorders4. Qualitative leukocyte disorders5. Quantitative platelet disorders6. Qualitative platelet disorders7. Pancytopenia8. Coagulation disorders9. Immune-mediated blood disorders10. Transfusion reaction

ANEMIA (Decreased hemoglobinAnd hematocrit)

MCV

Low High

Iron deficiencyThalassemiaLead poisoningChronic disease

Folate deficiencyVitamin B12 deficiency

Aplastic anemiaPreleukemia (MDS)

Immune hemolytic anemiaLiver disease

Hypothyroidism

Iron deficiencyThalassemia

Lead poisoningChronic disease

Sideroblastic Anemia

Normal

RECTICULOCYTE COUNT

High Low

Anemia can be categorized by MCV (high or low) or

mechanism (are you making too few or destroying too

many or losing red cells

BILIRUBINWHITE CELL ANDPLATELET COUNTNormal

High

Hemorrhage

Hemolytic anemia

COOMBS TEST

Low

NormalIncreased

Bone marrowDepressionMalignancyAplastic anemiaAcquired

Pure red cell aplasiaDiamond Blackfan AnemiaTransient erythroblastopenia Childhood

Infection

Negative Positive

a. CorpuscularExtracorpuscular

Autoimmune hemolytic anemiaPrimarySecondary (e.g., connective tissue disease, drugIsoimmune hemolytic diseaseRh, ABO mismatched transfusion

HemoglobinopathiesHemoglobin electrophoresisEnzyme assaysMembrane defectsAutohemolysisOsmotic fragility

b. Extracorpuscular

IdiopathicSecondaryDrugsInfectionMicroangiopathic

Morphology matters

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Positive Isoimmunization (ABO, Rh, minor blood group, e.g., Kell)

COOMBS TEST

Negative RETICULOCYTE COUNTSubnormal Pure red cell aplasia

Normal or Elevated

MCV

Low Normal or High

Chronic intrauterineblood loss

Alpha Thalassemia syndromes

BLOOD SMEAR

Normal Abnormal

Cont’d

Anemia in the newborn

Normal Blood Smear Abnormal Blood Smear

Rare miscellaneous causesHexokinase deficiencyGalactosemia

Blood lossIatrogenic (samplingFetomaternal/fetoplacental)Twin to twinInternal hemorrhage

Infection, e.gHIVToxoplasmosisCMVRubellaSyphllis

Hereditary spherocytosisHereditary elliptocytosisPyruvate kinase deficiencyG6PD deficiencyDICVitamin E deficiency

Hb MCV RDW FEP Ferritin Ser. Iron TIBC

IDA

Anemia ofChronic Infection

N N N or N or

Beta Thal

N N N or N N

Studies in Microcytic Anemias

THE HISTORY AND PHYSICAL MATTER!

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Hemoglobinopathies:-Quantitative or Qualitative

Sickle Cell Disease:- 1 in 600 African Americans at birth- Autosomal recessive trait- Three major genotypes comprise SCD: HB SS, HB SC, Hb Sthal- Crises include: VOC; Stroke; Priapism; ACS; Splenic Sequestration;Aplastic crisis

- TCD screening for stroke prevention- Importance of Newborn screening

Thalassemias:- Beta and Alpha Thalassemias- Clinical features of Beta thal major- Freq of one or two gene deletions of Alpha gene is 35% in AA- Individuals with both alpha thal trait and SS have less anemia and less stroke than

SS alone but same VOC

Sickle cells - first observationWalter Noel’s blood smear - Dec 31, 1904

Sickle Cell Disease: Pharmacologic Treatment

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Pathophysiology of SCD

In a red blood cell containing mostly Hb S…

…single Hb S molecules in free in solution; allows red cell to be soft, round, and deformable

When oxygenated…

+ O2

- O2

- O2

…Hb S molecules polymerize into long fibers; mishapen, dehydrated and adherent sickle cells.

When deoxygenated

+ O2


Pathophysiology of SCD

1. Molecular pathology

2. Biochemical pathology

3. Cellular pathology

4. Vascular pathology

5. Clinical pathology


Pathophysiology of SCDConsequences of Hb S polymerization and RBC sickling

• Red cell injury• Hemolysis• RBC dehydration and dense cell formation• Adhesion of RBC to endothelium• Formation of heterocellular aggregates (WBC, ISC)

• Vaso-occlusion

• Local hypoxia, increased Hb S polymer formation

• Propagation of vaso-occlusion in adjacent vasculature

• Deregulations of vasomotor tone by vasodilator

mediators (NO)


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Molecular pathology of SCDRegular Hemoglobin Genes and Products


F: a2 g2

A2: a2 d2

A: a2 b2

< 2%

< 3%

96%

Hemoglobins by age > 1 yr

Molecular pathology of SCDHemoglobin Genes and Products in SCD-SS


Gower 1: z2 e2

Gower 2: a2 e2

Portland: x2 g2

------------------

F: a2 g2

A2: a2 d2

S: a2 bs2

2-20%

3%

80-95%

Hemoglobins in SS by age > 1 yr

Molecular pathology of SCDThe sickle mutation


GAG

Glutamic acid

GTG

Valine

The bs Mutation

The same mutation found in all

bs genes around the world

6th Codon of b-Globin Gene

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RBC containing mostly Hb S

- O2

+ O2

+ O2

RBC containing mostly normal Hb

+ O2

- O2

oxygenated deoxygenated

oxygenated deoxygenated

Clinical Pathology of SCD

1. Anemia

2. Vaso-occlusion

3. Acute/Chronic organ damage



1. Anemia• Chronic intravascular hemolytic anemia

• Acute episodes of severe anemia Transient red cell aplasia (parvovirus B19)

Acute splenic sequestration

Acute hemolysis (“hyperhemolysis”)


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2. Vasoocclusive complications

• Microvascular occlusion clinically silent

• Macrovascular occlusion acute ischemic/infarctive damage

pain episodes stroke priapism acute chest syndrome renal papillary necrosis splenic infarction



3. Chronic organ damage

• Splenic dysfunction high risk of bacterial infection

• Progressive dysfunction of: lungs - pulmonary hypertension kidneys - proteinuria, renal failure gallbladder - gallstones eyes - proliferative retinopathy joints - osteonecrosis, arthritis heart - CHF/pulmonary hypertension


Pathophysiology of SCDVasoocclusion (1)

A. Prolongation of the RBC microvascular transit time caused by:

Enhanced red cell adhesion to endothelium and heterocellular aggregate formation

Abnormal cation homeostasis with cell dehydration, dense-cell formation, and

irreversibly sickled cell formation

Abnormal vasomotor tone favoring vasoconstriction


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Pathophysiology of SCDVasoocclusion (2)

B. Reduction in delay time to HbS polymer formation caused by:

Red-cell deoxygenation

Increase in intracellular HbS concentration

Low concentrations of protective Hb types (eg, HbF, HbA2)

Fall in pH

C. Miscellaneous potential modulators

Free-radical release and reperfusion injury

Coagulation activation with proadhesive thrombin formation


1. In vitro gelation studies have shown that Hb F

is effective inhibitor of gelation.

2. Patients with high Hb F levels (> 20%) documented

to have mild clinical course.

3. Patients with S-HPFH produce 25-35% Hb F in every

RBC beyond infancy, and are clinically asymptomatic.

Effect of Hb F on SCD

Hydroxyurea Therapy in Sickle Cell Disease

Hem Onc clinics Kuypers 2014

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Figure 1Pediatric Research (2014) 75, 196–204 doi:10.1038/pr.2013.227

Effect of Hb F on SCD


Beneficial RBC Effects of HU Treatment in SCD-SS

Increase in F-cell numbers and Hb F concentration per F cell

Inhibition of cation depletion and dense-cell formation

Reduction in stress reticulocytes and hemolytic rate

Increased deformability with improved rheology

Inhibition of sickle red cell-endothelium adhesion

Inhibition of sickle erythrocyte adhesion to extracellular

matrix components, including fibronectin,thrombospondin,

and laminin


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• Quantitative reduction in leucocyte count

• Qualitative changes in leucocytes, including reduction in

leucocyte-free-radical production and activation marker

L-selectin

• Reduction in soluble VCAM-1 concentrations (indicative of

decreased endothelial activation)

• In-vivo NO release


Beneficial Non-RBC Effects of HU Treatment in SCD-SS

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Aplastic AnemiaSEVERITY

Moderate aplastic anemia is defined as pancytopenia with the following findings: hypocellular bone marrow aspirate and biopsy and granulocyte count >500/mm, or platelet count>20,000/mm, or red cell transfusion dependency.

Severe aplastic anemia is defined as pancytopenia with the following findings: granulocyte count <500/mm; platelet count, <20,000/mm; reticulocyte count,

<20,000/mm; and bone marrow aspirate and biopsy show aplasia (<25% hematopoietic cells remaining).

Treatment: BMT/ATG-CSA +/- Eltromopag (Promacta)

Aplastic Anemia: Congenital vs. Acquired

Features of Acute and Chronic ITP

Feature Acute Chronic

AgeSex distributionSeasonal predilectionAssociated autoimmuneConditions (e.g., SLEOnsetPlatelet countEosinophilia andLymphocytosis

Antiplatelet antibodiesDurationProgress

Children 2-6 years of ageEqualSpringtime~80%UncommonAcute<20,000/mmCommon

Frequent<12 monthsSpontaneous remission in80% of cases

AdultsFemale: male 3:1NoneUnusualMore commonInsidious40,000-80,000/mmRare

Infrequent12 months +Fluctuating chroniccourse

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Qualitative Inherited Platelet Disorders• Adhesion– Bernard-Soulier• Aggregation– Glanzmann’s• Secretion– E.g. Gray Platelet Syndrome

Glanzmann’s Thrombasthenia• Rare Condition• Inherited absence of GPIIb/IIIa (AR)• Severe Bleeding manifestations• GPIIb/IIIa a key platelet glycoprotein required for aggregation• Absence of aggregation with ADP, Epi, Collagen• Normal ristocetin

Bernard-Soulier• Rare inherited bleeding Disorder: AR• Lack of GPIb which is necessary for the formation of the hemostatic plug by binding to subendothelial von Willebrand factor• Aggregation with ADP, Epi and collagen; absent Ristocetin

. Giant Platelets

PTT

PT Prolonged

Prolonged Normal

TT

Normal Prolonged

Liver diseaseVitamin KDeficiencyCirculatingAnticoagulantCoumadin effect

AfibrinogenemiaDysfibrinogenemiaDisseminatedIntravascularCoagulationHeparin effect

F XIIIdeficiency

Normal PT

Prolonged Normal

F VII,IIDeficiencyFII, XI, VIII,IX

DeficiencyCirculatingAnticoagulantHeparin effectKininogen Deficiencies

Inherited Coagulation Factor Disorders

Associated

WithBleedingEpisodesFactors Deficiency Genetics BT APTT PT

AfibrinogenemiaIIV (parahemophilia)VIIVIII Hemophilia A

von Willebrand's diseaseTypes 1 and 11Type 111

1X (hemophilia B)XX1 (hemophilia c)X11X111

ARARARARXLR

ADARXLRARARADAR

PPPNP

N/PPPPPPN

NNNNN

PPNNNNN

PPPPN

NNNNNNN

++++++++

++++++++++-+

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Von Willebrand Disease (vWD):

- autosomally inherited disorder caused by deficiency (type1) , dysfunction (type 2) or complete absence (type 3) of VWF.- vWF – a large multimeric protein produced in megakaryocytes and endothelial cells as pre pro vWF.-Most common hereditary bleeding disorder - biochemical evidence in 1-2 % of population & bleeding in 0.1%- Type 1 commonest (70-80%) – FVIII dec., vWF:ag dec., R-Co (vWF activity) dec., RIPA induced plt agg N or

Dec.,- Acquired vWF occurs in- Wilms tumor; hypothyroidism; myeloprolif. Dis; angiodysplasia.- Bleeding disorder as opposed to coagulation disorder – in terms of clinical presentation

Lab differences in vWD and Hemophilia

- aPTT Normal or prolonged in vWD Prolonged in Hemophilia- Factor VIII Borderline or decreased Decreased or absent- vWF Ag Decreased or absent Normal or increased- vWF multimers Normal or abnormal Normal

Clinical Indicators of Hypercoagulable State

Family history of thrombosisRecurrent spontaneous thrombosesThrombosis in unusual sitesThrombosis at an early ageResistance to anticoagulant therapyCoumarin necrosis syndromeRecurrent spontaneous abortionsThrombosis during pregnancyMigratory superficial thrombophlebitis

Antiplatelet agentsa. Aspirin 5-10 mg/kg/dayb. Dipyridamole 3-5 mg/kg/day

Coagulation Made Easy

The PTT Pathway The PT Pathway

Rather than thinking about the intrinsic and the extrinsic

pathways, think about the PTT and the PT pathways.

Adapted from Alice Ma MD/UNC

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X


The PT and the PTT pathway

meet at Factor X, because “X”marks the spot.


V

X


Factor V is a cofactor for Factor

X, and you can remember this

because V fits into the notch of

the X.


V

X

Prothrombin Thrombin


Factor Xa converts prothrombin (Factor II) into thrombin, the

most important enzyme on the planet.

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V

X


Fibrinogen Fibrin


Thrombin, among other things,

converts the soluble molecule

fibrinogen into a solid fibrin clot.

The Common Pathway = Small Bills

V + X

II = prothrombin

I = fibrinogen

You can remember the factors in the common pathway by remembering the bills in your

wallet smaller than a $20. Don’t forget the $2 bill!

Coagulation Made Easy: The PT


Fibrinogen Fibrin

7

V

X

The PT PathwayPT has one less letter than PTT, and

PT values are shorter than PTT values,

because the pathway is shorter. It

means that the PT pathway is also

shorter. This means that there’s fewer

steps to remember, and this is lucky, so

the lucky PT pathway uses lucky

Factor 7 to activate Factor X.

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Coagulation Made Easy: The aPTT


Fibrinogen Fibrin

V

X

XIIXI

IXVIII

The PTT pathway has all those

hideous roman numerals. . .

How are we going to remember them?.

.

The PTT Pathway



Fibrinogen Fibrin

T

NE

TV

X

E

The PTT Pathway

Well, just remember that the PTT is a

basic TENET of hematology.

TENET stands for. . .



Fibrinogen Fibrin

Twelve

Nine

Eight

TenV

X

Eleven

The PTT Pathway

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Coagulation Made Easy: PT and PTT Both Prolonged

V

X

Prothrombin (II)

Fibrinogen


These factors are in the

common pathway.

Coagulation Made Easy: Only PT Prolonged

7

Deficiency of Factor VII will prolong the PT but not the PTT.

Coagulation Made Easy:

Only PTT Prolonged

Twelve

Nine

Eight

Ten

Eleven

Deficiencies of Factors 12, 11, 9, and

8 will prolong the PTT and not the PT.

Remember that Factor 10 is in the

common pathway, and affects BOTH

the PT and the PTT.

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• Deficiencies of Factor XI, IX,

VIII, VII. X, V, prothrombin, and

fibrinogen are clinically

significant.

• Inhibitors of these factors are

clinically significant for bleeding.

• Deficiency of Factor XII, and the

presence of the lupus

anticoagulant are not.

XII

XI

IX

X

VIII VII

Thrombin

V

Fibrinogen Fibrin

What Matters Clinically

Coagulation Made Easy: The Mixing Study

• Useful to differentiate etiologies of prolonged clotting in a coagulation assay.

• Patient’s plasma is mixed 50/50 with normal plasma. Coagulation assay is repeated.

• If “substantial” correction is noted after mix, suspect clotting factor deficiency, because you replaced deficient factors in the patient plasma with normal factors from the normal plasma.

• If no or not full correction is seen, suspect an inhibitor, because you added the inhibitor (think of this as an anticoagulant) in the patient plasma which inhibits clotting in the normal plasma.

Paroxysmal Nocturnal Hemoglobinuria:

- PIG-A mutation with clonal expansion of hematopoietic cells- Absence of surface CD55/CD59- leads to chronic complement mediated IV hemolysis- Macrocytosis with erythroid dysplasia may evolve in severe AA- Major clinical features:

> PNH with hemoglobinuria and anemia> Bone marrow failure leading to AA – 10%; occ. Leukemia transformation> Venous thrombosis (often cause of mortality)

Rx:> HSCT definitive> Ecluzimab> Cyclosporine / ATG> Support with GCSF/ PRBC Tx/ anticoagulant Rx

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Leucocyte Function Disorders:- About 20% of immune deficiencies- Adhesion deficiencies: LAD 1 - Delayed umbilical cord separation/omphalitis

- Persistent neutrophilia but no pus - Recurrent skin infections; NEC

LAD 2 - Mental Retardation; short stature- WBC 30 to 100K with no pus- Less severe infections

- Chemotaxis: Hyper IgE syndrome(job) - Chronic eczema; delayed teeth shedding; - Recurrent abscesses; Chronic Candida infections- Very high IgE levels; decreased chemotaxis but normal bactericidal fn.

- Degranulation: Chediak Higashi: - oculo--cutaneous albinism; recurrent abscesses; neurol. Features- Death in early childhood- Large granules in in granulated cells and melanosomes; pancytopenia

- Oxidative metabolism: CGD - 65% X linked; absent respiratory burst oxidase; NBT test / Rhodamine- Large nodes; recurrent suppurative infections; granulomas.- Prophylactic antibiotics and rhIFN- Gamma RX

Leukemias:

- Acute Lymphoblastic leukemia: (ALL) 75% - Acute Myeloblastic Leukemia : (AML)- 20%- Acute Undifferentiated Leukemia: <0.5%

Chronic myeloid leukemias: 3% of all childhood leukemias Philadelphia Chr positive ; Juv. Myelomonocytic leukemia- 3-4 cases per 100,000. Peak incidence 2- 5 yrs of age- Account for 25- 30% of all childhood cancers

Hodgkins Lymphoma:- Incidence: 12 per million <20 years; 32 per million 15-19 yrs. - Associated with EBV infection (mixed cellularity type)- Classic hall mark RS cell

Non – Hodgkins Lymphoma: - 6-8% of all malignancies <20yrs age; M:F 2-3:1 Median age 10 yrs- About 70% present with advanced stage disease including extranodal involvement- 25% have Anterior mediastinal mass- Overall survival rates 80-90% EFS

Relative Frequency of Common Childhood Brain Tumors

Location and HematologyFrequency (%)

Supratentorial

Cerebral hemisphereAstrocytomaEpendymoma

GlioblastomaMeningiomaOther

Sella/chiasmCraniopharyngioma

Pituitary adenomaPituitary adenomaOptic nerve gliomaOther

TotalInfratentiorial

CerebellumMedulloblastomaAstrocytomaMeningioma

Brain StemAstrocytomaEpendymomaGlioblastoma

OtherTotal

65544

9322__40

25182

5532___60

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Common Solid Tumors of Childhood

Neuroblastoma: Most common tumor in infancy. 50% are under age 2 ; 75% under 4. - Most common presenting feature- Abd. Mass; with metastases at onset in 75%- Associated Conditions: NF; Hirschsprungs; Heterochromia; Phaeo;Fetal -Hydantoin and alcohol synd.- Increased urine/serum catecholamines . -Opsoclonus-myoclonus

Wilms Tumor: 6% of all childhood cancers. Peak incidence 3- 4 yrs age- 12- 15% associated with congenital anomalies. – aniridia(with 11p13 del); hemihypertrphy, Beckwith –Wiedeman; genito- urinary abn.- S/s: Abd. Mass; hematuria; hypertension; polycythemia; Acq. VWF

Osteosarcoma: Bone tumors account for 2% of all childhood tumors.- Retinoblastoma gene (Rb) Chr 13q14 is implicated on osteosarcoma- Half or more on femur, usually around knee- radioresistant- Amputation/limb spare surg with Chemo

Retinoblastoma: 1/3 cases bilateral and Dx ed during 1st yr of life; 40% hereditary (Auto Dominant)- Most children with Rb have no other abn. - Rb gene assoc, with Soft tissue sarcoma; osteosarc; Adenoca of breast; SCLC- Survivors of Rb have very high risk of sec malig.- Common s/s : Leukocoria; strabismus;Red painful eye.

BMT:Transfusion associated GVHD prevention: Gamma radiated blood; Leucocyte depletion; Selective T cell depletion; UV radiation.

Infections: in first 30 days post Tx: Bacteremia; Invasive fungal; Reactivated herpes simplex- 50- 120 days: Protozoal (PCP; Toxo); Viral – CMV; adeno EBV HHV6; Fungal- After 120 days: Sino- pulmonary infns; Cutaneous Herpes zoster

GVHD: Acute: in first 100 days usually within 30- 40 days; Chronic: after 100 days. Biopsy may be req to differentiate from infection.

Late sequelae of BMT: Growth failure; Chr. GVHD; MEN; second malig; Sterility; cataracts; renal insuff.; Obstruc./ restric. Pulmo disease; cardiomyopathy; Aseptic necrosis of bone; Leukoencephalopathy

Oncologic emergencies: Tumor lysis; Hyperleucocytosis; SIADH; febrile neutropenia; bleeds; typhlitis;

Chronic Effects of Sickle Cell Disease

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Adverse Effect Estimated Risk

Febrile reaction 1/300

Urticaria /other cutaneous reaction 1/50-100

RBC alloimmunization 1/100

Mistransfusion 1/14000-19000

Hemolytic reaction 1/6000

Fatal Hemolysis 1/1000,000

TRALI

HIVHep BHep CAnaphylaxis

1/5000

1/2000,000- 3000,0001/100,0001/1000,0001/20,000 – 50,000

Risks in transfusion per unit Transfused (US)

*Use irradiated cellular products to prevent GVHD especially in preterms and immune compromised

1. Microcytosis in a newborn may indicate all of the following except:

a. A-thalassemia traitb. B-thalassemia traitc. Iron deficiency anemiad. Hemoglobin H disease

2. Persistent reticulocytosis in a newborn suggests the presence of all of the followingexcept

a. Hemolysisb. Hypoglycemiac. Blood lossd. Hypoxiae. G6PD deficiency

3. Fetal to maternal bleeding is suspected in a baby with type A blood to a mother withtype O blood. Which of the following tests may be a strong indicator of this hemorrhage?

a. Positive Coombs test on the babyb. An Acid elution test on the motherc. A rising anti A or anti B titer in the mother following deliveryd. Flow cytometry

4. B-thalassemia trait can be differentiated from iron deficiency because in thalassemia:

a. The RBC count is lower and the MCV is lowerb. The RBC count is higher, the MCV lower and A2 higherc. The RBC count is lower, the MCV lower and A2 higherd. The RBC count is lower, the MCV lower and the A2 normal

5 In thalassemia, iron absorption is:

a. Increasedb. Decreasedc. Unchanged

6 Which of the following newborn screening results is suggestive of sickle cell disease

a. FASb. FSAc. FSCd. FAe. B, c

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Match the site of absorption with the following vitamins and minerals:

a. Duodenumb. Terminal ileumc. Jejunum

7. Iron

8. Vitamin K

9. Vitamin B12

Match the anemia associated with iron deficiency and chronic disorders with the appropriateLaboratory findings:

a. Iron deficiency anemiab. Anemia resulting from chronic disorders (Inflammation, infection) c. Bothd. Neither

10. Reduced serum iron concentration11. Increased erythrocyte protoporphyrin12. Normal or increased total iron binding capacity13. Normal or increased iron stores14. Ferritin less than 25 ng/ml.15. Ringed Sideroblasts in the bone marrow.16. Reduced macrophage iron.

17. In anemia of chronic disorders, serum iron is low because:a. Iron absorption is defectiveb. Erythropoietin response to anemia is inadequate.c. Iron release from macrophages to erythroblasts is defectived. There is increased iron excretion

18. Increased number of the following cells in a bone marrow aspirate of aplastic anemiaIs a poor prognostic indicator:

a. Promyelocytesb. Megakaryocytesc. Lymphocytesd. None of the above

19. Cyclic neutropenia is characterized by all of the following except:

a. Some cases progress to AML if treated with G-CSFb. It is linked to mutation of neutrophil elastase with G-CSFc. Recurring skin infection is commond. G-CSF will improve oscillation of ANCe. GCSF will improve peripheral blood and reduce the signs and symptoms of

Neutropenic nadir

20. Congenital causes of thrombocytopenia include:a. Giant Hemangiomab. Rubellac. Absent radiid. Trisomy syndromee. All of the above

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21. A patient with normal platelet count; normal PTT and prolonged PT has which of the following deficiencies:

a. Factor VII deficiency onlyb. Factors II or VII deficiencyc. Factor V and VII deficiencyd. All of the above

22. All of the factors are produced in the liver except

a. Factor Vb. Antithrombin IIIc. Factor VIIId. Protein Ce. VWF

23. All are true of Aplastic crises except:a. It is caused by B19 parvovirus infection which decreases erythroid activity in the hematopoietic systemb. B19 parvovirus causes Fifth disease and does not cause decrease erythroid activity in the hematopoietic system in

children with sickle cell disesec. Often associated with reticulocytopeniad. Can occur in G6PD deficiency and hereditary spherocytosis

24. All of the following statements are False except:

a. Performing Transcranial Doppler(TCD) is needed for diagnosing stroke in SCDb. A high TCD value suggests high risk of strokec. A low TCD value suggests high risk of stroke in patients with sickle cell traitd. A normal TCD value suggests high risk of stroke

25. On newborn screening for sickle cell disease the following patterns suggest sickle cell trait a. Hb bands F, Sb. Hb F, S, Cc. Hb F, A, Sd. Hb F, A, Barts

26. The nonemetogenic chemotherapeutic agent is:a. Ifosfamideb. Vincristinec. Actinomycin-Dd. Methotrexatee. Cytarabine

27. The clinical presentation of AML in infants less than 2 years of age includes all of the Following characteristics except:

a. Disseminated intravascular coagulationb. Spontaneous remissions occurring frequently in patients with Down Syndromec. t(9;11) with poor, and t(4;11) with favorable prognosisd. Higher leukocyte counts, hepatosplenomegaly and skin lesionse. Petechiae

28. Toxicities of vincristine include all of the following except:a. SIADHb. Insomniac. Constipation and urinary retentiond. Hypotensione. Neurotoxicity, seizure

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29. Testicular relapse in acute lymphoblastic leukemia is most common with all of theFollowing cases of ALL except:

a. White count more than 20,000b. Lymphomatous presentation, T-cell diseasec. CNS involvementd. Significant thrombocytopenia

30. The single greatest determinant of susceptibility to bacterial and fungal infections inA cancer patient is:

a. Colonizing flora and defective skin defenseb. Total white countc. Level of circulating granulocytesd. Circulating immunoglobulin level

31. Infections occurring during the first month after bone marrow transplantationInclude all except:

a. Interstitial pneumonia due mainly to cytomegalovirus before the age ofGanciclovir prophylaxis

b. Pneumocystis jiroveci infectionc. Bacterial sepsisd. Herpes simplex and herpes zostere. Fungal infections

32. Graft versus host disease (GVHD) is caused by and is dependent on all except:a. Humoral antibodiesb. Nature donor T-lymphocytesc. The degree of genetics disparityd. Recognition of non-HLA transplantation antigens by donor T-cellse. Tumor necrosis factor/TNF-1

33. Bone marrow transplant in ALL is strongly recommended in all of the followingsituations except:

a. Persistent minimal residual diseaseb. Early relapsec. Infant ALL with 11q23 rearrangementsd. Bone marrow relapse one years after completion of maintenance therapye. Isolated testicular relapse while receiving chemotherapy

34. Acute tumor lysis may include all of the following except:

a. Hyperuricemia, treated with urate oxidaseb. Hyperkalemiac. Hyponatremia as a result of SIADHd. Hyperphosphatemia with hypocalcemiae. Seizures

35. A history of progressive cranial nerve dysfunction, gait disorder, and cerebellar andPyramidal tract abnormalities is suggestive of:

a. Medulloblastomab. Astrocytomac. Brain stem gliomad. All of the above

36. All of the following are common brain tumors in 2-12 year olds except:

a. Cerebellar astrocytoma (infratentorial)b. Cerebellar astrocytoma (supratentorial)c. Medulloblastoma (infratentiorial)d. Brain stem glioma (infratentiorial)

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37. The most common primary site of osteosarcoma is:a. Distal femurb. Proximal tibiac. Proximal humerusd. Pelvis

38. The primary sites of metastases of osteosarcoma are:a. Lungs and bone marrowb. Lungs and liverc. Lungs and boned. Lungs and brain

39. Clinical presentation of neuroblastoma may include:a. Bone pain and limpingb. Diarrhea, abdominal pain, abdominal mass, anorexia, and weight lossc. Unexplained hypertensiond. Proptosise. Oposclonus-myoclonus syndromef. All of the above

40. The most common presenting symptom of retinoblastoma is:

a. Painful eyes with glaucomab. Strabismusc. Leukocoriad. Blindness

41. Which of the following are included in the etiology of brain tumors?

a. Postnatal radiation exposureb. A late effect of treatment of other cancers, particularly ALLc. A component of Li-Fraumeni syndromed. Increased incidence with neurofibromatosis, tuberous sclerosis and primary

immunodeficiency syndromee. All of the above

42. Neuroblastoma metastasizes to all except:a. Regional and distant Lymph nodesb. Bone marrowc. Liver and Skind. Lungs

PowerPoint Presentationnysaap.org/blog/2018HemOnc.pdf · 8. Coagulation disorders 9....

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Transcript of PowerPoint Presentationnysaap.org/blog/2018HemOnc.pdf · 8. Coagulation disorders 9....