PEDIATRIC HEMATOLOGY

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PEDIATRIC HEMATOLOGY

• Unit 4 Part 3 Module 3

Prepared by C. Sargo RN (EC) Reviewed by Maj.
Quinn RN (EC)
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REFERENCES

• C290- Nelsons Essentials of Pediatrics
• C306- Toronto Sick Kids Manual
• C277- Toronto Notes
• C291- Primary care for PAs
• Class Handout

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OUTLINE

• Normal Pediatric Hematology Values
• Physical Signs of Anemia in Children
• Iron Deficiency Anemia
• Hemolytic Anemias
• Major Hemaglobinopathies
• Bleeding Disorders
• White Cell Disorders -

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NORMAL PEDIATRIC HEMATOLOGY VALUES

• Birth
• - Hbg - mean 16.8 (13.7-20.1)
• - HCT mean 55 (45-65)
• - Wbc -mean 18,000( 9000-30,000
• - Retics - mean 5.0
• 3mos
• - Hbg - mean 12.0
• - HCT mean 36
• - Wbc -mean 12,000
• - Retics - mean 1.0

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NORMAL PEDIATRIC HEMATOLOGY VALUES

• 6mos - 6 years
• - Hbg - mean - 12.0
• - HCT mean - 37
• - Wbc -mean - 10,000
• - Retics - mean -1.0
• 7-12 yrs
• - Hbg - mean - 13.0
• - HCT mean - 38
• - Wbc -mean - 8,000
• - Retics - mean -1.0

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PHYSICAL SIGNS OF ANEMIA

• Skin
• - Jaundice- hemolytic anemia
• - Petechiae - purpura- autoimmune hemolysis with
  autoimmune thrombocytopenia, bone marrow
  infiltration, hemolytic uremic syndrome
• - Vitiligo - Vitamin B12 deficiency
• - Hyperpigmentation/café-au-lait spots - Franconi
  anemia
• - Butterfly rash- SLE antibodies
• - Erythematous rash- Epstein barr virus

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PHYSICAL SIGNS OF ANEMIA

• Head
• - Frontal bossing of cranium- severe iron
  deficiency anemia, Thalassemia major
• - Microcephaly - Franconi anemia
• Eyes
• - Microphthalmia - Franconi anemia
• - Blue sclera - iron deficiency

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PHYSICAL SIGNS OF ANEMIA

• Mouth
• - Glossitis- iron deficiency, B12 deficiency
• - Stomatitis - iron deficiency
• Chest
• - Heart murmur- severe anemia

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PHYSICAL SIGNS OF ANEMIA

• Abdomen
• - Hepatomegaly - hemolytic anemia, anemia of
  chronic disease,
• - Splenomegaly- hemolytic anemia, sickle cell,
  thalessemia,
• lymphoma, Epstein barr virus
• - Enlarged kidneys- Franconi anemia

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PHYSICAL SIGNS OF ANEMIA

• Extremities
• - Spoon nails - iron deficiency
• - Beau lines in nails- heavy metal intoxication,
  severe illness
• - Mees lines in nails- heavy metals, severe
  illness, sickle cell

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PHYSICAL SIGNS OF ANEMIA

• Neurological
• - Irritability, apathy, poor concentration - iron
  deficiency
• - Peripheral neuropathy- B1, B12 deficiency, lead
  poisoning
• - Ataxia, loss of vibration/position sense- B12
  deficiency
• - Stroke- sickle cell anemia
• Small stature
• - Anemia of malnutrition, HIV, Franconi anemia

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IRON DEFICENCY ANEMIA

• A microcytic, hypochromic anemia
• Decreased ferritin, decreased TIBC, marrow
  deplete of stainable Fe2
• Most common cause of childhood anemia worldwide
• Full-term infants exhaust Fe 2 reserves by 5-6
  months age
• Preterm infants have lower reserves exhaust by
  2-3 months of age

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IRON DEFICENCY ANEMIA

• Commonly presents
• - Between 6 months 3 years
• - Ages 11-17 years periods of rapid growth and
  increased Fe 2 requirements
• - Adolescents at risk - poor diets, menstrual
  losses
• - Can cause irreversible effects on development
  if untreated

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IRON DEFICENCY ANEMIA

• Etiology
• - Vegan diet
• - Secondary to poor intake of iron-rich foods (
  typically in bottle-fed infants (6-24 months)
  receiving large volumes of cows milk)
• GIT blood loss
• - Cows milk allergy occult bleeding
  protein-losing enteropathy secondary to
  inflammation enteropathy secondary to
  inflammatory bowel disease

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IRON DEFICENCY ANEMIA

• Management
• - CBC, diff, smear, Iron, TIBC, Ferritin
• - Determine underlying cause
• - Encourage diverse, balanced diet - iron rich
  foods /formula
• - Oral iron therapy ferrous sulfate 3mg/kg/day
  BID-TID for 3 months
• - Close follow up to monitor dietary intake,Hbg ,
  ferritn for response to RX

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IRON DEFICENCY ANEMIA

• Prevention
• - Breast-fed infants after 6 months, give
  iron-fortified cereals and iron-rich foods
• - Non-breast fed infants give iron-fortified
  formula from birth
• - Premature infants start iron supplements at
  6-8 weeks of age and continue until 1 year old

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HEMOLYTIC ANEMIAS

• Intrinsic RBC disorders
• - Hereditary spherocytosis
• - G6PD( glucose-6-phosphate dehydrogenase
  deficiency)
• Extrinsic RBC disorders
• - ABO, Rh incompatibility

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INTRINSIC RBC DISORDERS

• Spherocytosis
• - Red cell membrane disorder, causes a sphering
  of red blood cells which are removed by the
  spleen
• - Genetic base- autosomal dominant (positive
  family history)
• - High spontaneous mutation rate (no family
  history)
• - Clinical presentation variable from
  well-compensated, mild hemolytic anemia to severe
  hemolytic anemia with growth failure,
  splenomegaly, and chronic transfusion
  requirements especially in infancy

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INTRINSIC RBC DISORDERS

• Glucose-6-Phosphate Dehydrogenase (G6PD)
  Deficiency
• - X-lined recessive, different variants of the
  disease
• - Enzyme deficient red blood cells
• - Higher prevalence in Mediterranean's, Blacks,
  Orientals
• - Presents with acute hemolytic anemia with
  jaundice and dark urine
• - Diagnosis- G6PD assay, Blood film- Heinz
  bodies

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INTRINSIC RBC DISORDERS

• Glucose-6-Phosphate Dehydrogenase (G6PD)
  Deficiency
• - Management is supportive hydration,
  transfusion,
• phototherapy
• - Prevention of acute episodes Avoid known
  oxidants (e.g. fava beans, ASA, antimalarials,
  sulfonamides

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EXTRINSIC RBC DISORDERS

• ABO Blood Group Incompatibility
• - Commonest cause of iso-immune hemolysis in the
  newborn
• - Results from blood group differences between an
  sensitized mother and fetus
• - Sensitized mother produces IgG antibodies that
  cross the placenta by active transport and
  hemolyze fetal RBC,s
• - Mother is sensitized by prior exposure to A or
  B antigens
• - ABO incompatibility rarely produces significant
  anemia in utero but may cause more significant
  anemia and hyperbilirubinemia in the newborn

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EXTRINSIC RBC DISORDERS

• Rh factor Incompatibility
• - Rh system consists of 5 antigens- C,D,E, c, e,
• - In most cases of Rh sensitization it is the D
  antigen of the fetus which sensitizes the Rh
  negative mother resulting in IgG antibody
  production during the first pregnancy
• - The first affected infant in the1st pregnancy
  may not manifest any disease in utero but may
  manifest hemolytic disease in the newborn period
  ( anemia hyperbilirubinemia)

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EXTRINSIC RBC DISORDERS

• Rh factor Incompatibility
• - Subsequent pregnancies are affected by earlier
  onset of hemolysis in utero
• - Leads to fetal anemia, heart failure,
  elevated venous pressure, portal vein obstruction
  and hypoalbuminemia
• --gtfetal hydrops
• - Fetal hydrops- ascites , pleural/pericardial
  effusions
• - Risk of fetal death high

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EXTRINSIC RBC DISORDERS

• Rh factor Incompatibility
• - Severity of hemolysis in utero is detected by
  assessing the quantity of bilirubin in amniotic
  fluid
• - Treatment depends on severity of disease and
  gestational age of infant
• - Intrauterine transfusions of O negative blood
  until lungs mature then deliver
• - Prevention - screen all mother prenatally
• - Rh -, mothers given anti-Rh-positive immune
  globulin at 28 weeks, post -partum ( 72 hours)

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SICKLE CELL ANEMIA

• Describes syndrome of hemoglobin SS, S-C, sickle
  cell thalassemia
• Identification of specific hemaglobin phenotypes
  important due to differences in frequency, type
  and severity of clinical complications (most
  severe is SS, least severe SD)
• SCA results from a single amino acid substitution
  valine for glutamic acid on the hemaglobin
  molecule

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SICKLE CELL ANEMIA

• Red blood cells sickle with low pO2, dehydration,
  fever, acidosis
• Acute intravascular sickling results in
  infarction of tissue
• Hemolysis causes chronic, well-compensated anemia
  (Hb 60-90 g/L)
• More common in Blacks and Mediterranean's

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SICKLE CELL ANEMIA

• Clinical Presentation
• - SC trait asymptomatic microscopic hematuria
• - SC disease after 10-12 weeks - fall in fetal
  Hb, anemia, jaundice, splenomegaly
• - Chronic compensated anemia
• - Recurrent crises

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SICKLE CELL ANEMIA Types of Crises

• Vaso-occlusive crises
• - Most common presentation
• - Due to obstruction of blood vessels by rigid,
  sickled cells ? tissue hypoxia
• ? cell death presents as pain and fever
• - Affects in any organ
• - Commonly in long bones of arms and legs, chest,
  abdomen, CNS (stroke), dactylitis (in young
  children

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SICKLE CELL ANEMIA Types of Crises

• Aplastic crisis
• - Depression of erythropoiesis, generally
  associated with infection (Parvovirus B19)
• Splenic sequestration
• - Sudden massive pooling of red cells in spleen,
  acute fall in hemoglobin, shock (increased
  reticulocyte count, decreased Hb)

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SICKLE CELL ANEMIA

• Functional Asplenia
• - Splenic dysfunction usually by 5 years
  secondary to autoinfarction
• - Susceptible to infection by encapsulated
  organisms (especially S. pneumoniae)

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SICKLE CELL ANEMIA

• Other Manifestations
• - Growth delay
• - Bony abnormalities
• - Avascular necrosis (AVN) of femoral head
• - Priapism (often results in permanent impotence
  in adults)
• - Stones
• - Acute chest crisis fever, chest pain,
  increased WBC count, pulmonary infiltrates

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SICKLE CELL ANEMIA

• Management - Acute crises
• - Supportive and symptomatic
• - Fluids (1 ½ maintenance)
• - Analgesia
• - Exchange/straight transfusions
• - Antibiotics
• - O2

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SICKLE CELL ANEMIA

• Management - Chronic ongoing care
• - Early aggressive treatment of infections,
  prophylactic antibiotics (daily oral penicillin)
• - Pneumococcal, meningococcal, Hepatitis B, Hib
  and influenza vaccines
• - Folate supplementation if macrocytic
• - Hydroxyurea if have frequent crises
• - Recurrent transfusion program if history of
  stroke
• - Genetic counseling

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BETA-THALASSEMIA MAJOR

• Defect in production of ß Hbg
• Leading to ineffective production and hemolysis
  of RBCs
• Increase in Hbg F
• Autosomal recessive inheritance
• Affects Asian and Mediterranean people

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BETA-THALASSEMIA MAJOR

• Clinical Presentation
• - Child 3-6 months
• - Severe anemia
• - Jaundice
• - delayed growth /development( hypogonadal
  dwarfism)
• - Hepatosplenomegaly
• - Expanded bone marrow cavity
• - Pathological fractures common

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BETA-THALASSEMIA MAJOR

• Investigations
• - CBC, smear, Hbg electrophoresis
• Treatment
• - Transfusions
• - Iron chelation to prevent overload
• - Bone marrow transplant

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IDIOPATHIC THROMBOCYTOPENIC PURPURA

• Peak age 2-6
• MF
• Caused by antibodies IgG or IgM that bind to
  platelet membranes ? splenic destruction of
  antibody-coated platelets
• Typically presents after viral illness or
  immunization 1-3 weeks prior to presentation

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IDIOPATHIC THROMBOCYTOPENIC PURPURA

• Clinical Presentation
• - Occurs in an otherwise well child
• - Sudden onset of petechiae, purpura, epistaxis,
  hematuria or GI hemorrhage
• - Usually no lymphadenopathy
• - Usually no hepatosplenomegaly
• - Rarely ITP may a presenting symptom of
  autoimmune disease (e.g. SLE)

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IDIOPATHIC THROMBOCYTOPENIC PURPURA

• Differential diagnosis
• - Leukemia
• - Drug-induced thrombocytopenia
• - HIV, infection (viral)
• - SLE

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IDIOPATHIC THROMBOCYTOPENIC PURPURA

• Lab work
• CBC - Thrombocytopenia with normal RBC, WBC
• Management
• - IVIG - 1g/kg/24 hr for 2 days
• - Prednisone 2-4 mg/kg/24 hr x 2 weeks
• - Must rule out leukemia before using prednisone
• - Splenectomy (only for life-threatening
  bleeding)

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NEONATAL THROMBOCYTOPENIA

• Neonatal alloimmune thrombocytopenia (NAIT)
• Mother mounts immune response against antigens on
  fetal platelets
• Diagnosis maternal serum (with immunoglobulins)
  reacts with fathers or childs platelets
• Treatment transfusion of infant with washed
  maternal platelets

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HEMORRHAGIC DISEASE OF THE NEWBORN

• Caused by vitamin K deficiency
• Factors II, VII, IX, X are vitamin K-dependent,
  therefore both PT and PTT are abnormal
• Presents at 2-7 days of life with GI hemorrhage,
  intracranial hemorrhage bleeding from a
  circumcision or umbilical stump
• Prophylaxis IM vitamin K administration at
  birth to all newborns

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HEMOPHILIA A

• X-linked recessive, 1/5000 males
• 5 times more common than Hemophilia B
• Factor VIII deficiency
• Severity determined by level of factor VIII,
  severity of bleeds, and presence of antibodies to
  factor VIII
• Mild (gt5 factor VIII)
• - Bleeding with significant trauma (e.g. surgery)
• - May go undiagnosed for many years

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HEMOPHILIA A

• Moderate( 1-5)
• - Moderate trauma to induce bleeding
• Severe (lt1 factor VIII)
• - Spontaneous bleeding or bleeding from minor
  trauma,
• - Manifests in infancy,
• - Hallmark hemarthrosis
• Treatment
• Factor VIII replacement
• DDAVP for mild disease

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HEMOPHILIA B (Christmas Disease)

• Factor IX deficiency
• X-linked recessive genetic disorder
• Treated with factor IX replacement or plasma
• Presentation same as Hemophilia A

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von WILLEBRANDS DISEASE

• Common disorder affecting 1 of population
• Abnormality in von Willebrand factor (vWF)
• Autosomal dominant (mild presentation more
  common ( 80)
• Autosomal recessive (rarer, more severe)
• SS - mucocutaneous bleeding, epistaxis,
  bleeding gums, heavy menstrual bleeding,
• DDAVP Rx of choice, also Humate P( vWB containing
  concentrate)

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LEUKEMIA

• Affects children ages 1-10 typically
• ALL type commonest (80)
• AML second commonest form ( 15)
• CML ( 5)
• Etiology is unknown

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LEUKEMIA

• SS
• - Fever, pallor, lethargy
• - Malaise, anorexia
• - Bone /joint pain
• - Petechiae, ecchymosis
• - Lymphadenopath, hepatosplenomeglay,
• - Anemia, neutropenia, thrombocytopenia

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LEUKEMIA

• Dx based on finding immature blast cells on
  either the peripheral blood smear, bone marrow or
  both
• Rx is with chemotherapy
• Prognosis ( in 2000)
• - Cure rate 50 with ALL except in the very
  young infant
• and 50 with AML ( Nelsons)

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LYMPHOMA

• Two types- Hodgkins, Non- Hodgkins
• Hodgkins
• - Etiology is unknown
• - Incidence increases during childhood and peaks
  late adolescence
• - Males gt Females (31) in early childhood, after
  puberty ratio 14

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LYMPHOMA

• Hodgkins (continued)
• - Presents as persistent painless lymphadenopathy
  ( cervical and supraclavicular , axillary nodes)
• - Persistent cough, SOB( mediastinal mass)
• - B symptoms- high spiking fevers, night sweats,
  weight loss
• - Pruritis

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LYMPHOMA

• Hodgkins (continued)
• Diagnosis
• - CBC, RFTs, LFTs, uric acid, ESR, Ca, aLP,
  phosphate for bone metastases
• - CXR
• - CT of chest, abdomen, pelvis
• - Biopsy of nodes
• - Bone marrow biopsy

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LYMPHOMA

• Hodgkins (continued)
• Treatment
• - High cure rate
• - Stage I-II - radiation or chemo local field
  radiation
• - Stage III-IV- combination chemotherapy
• - Relapse Rx - higher dose chemo bone marrow
  transplant