Pediatric Hematology

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Pediatric Hematology
Dr. Mariana Silva, MD.F.R.C.P.C. March 2008
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FETAL AND NEONATAL ERYTHROPOIESIS

• TABLE 1. Globin-chain development and composition

a This tetramer may be an epsilon tetrad. b
Fetal hemoglobin produced by adults has a
different amino acid heterogeneity of the gamma
chain at the 136 position than fetal hemoglobin
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Site of Erythropoiesis
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Hemoglobin Synthesis inFetus and Newborn

• Gower 1 and 2
• - present in yolk sac
• - 75 of early Hgb
• - undetectable after week 12
• Week 12 to 32 ? 90 Hgb F

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Hemoglobin Synthesis inFetus and Newborn (contd)

• The Switch is Hgb F to A
• Hgb F ? after week 32 by week 40 is 50-75
• by 6 month is 5-8 by 1 year lt 1
• Delayed Switch (? mechanism? ? Stress
  Erythropoiesis)
• . Maternal hypoxia
• . Small for Gestational Age
• . Infants of diabetic mothers

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Physiological Anemia of Infancy

• Gradual ? in Hgb after birth for 2 months,
• stable 2-4 month, then ?
• Physiologic as no symptoms of hypoxia and
• not nutritional
• Fetus - 10 weeks Hgb 9 gr/dl
• - 22-24 week, Hgb 14 gr/dl
• - 32-40 week, Hgb 16 gr/dl

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Physiological Anemia of Infancy (contd)

• age ? blood supply to placenta ?? Epo to
  maintain oxygen supply to infant ??Hemoglobin
  (Hgb)
• Oxygen delivery to fetus determines Hgb level at
  birth.
• Examples
• Small for gestational
• Infant of diabetic mother ? metabolic demands on
  fetus from ? glucose ?? oxygen needs ??Hemoglobin
• Infants of smokers ? fetal CO ?? oxygen
• available ?? Hemoglobin to compensate
• Infants gestated at ? altitudes ? inspired
• oxygen by mothers ?? Hemoglobin in newborn

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Physiological Anemia of Infancy (contd)

• Birth ? Hemoglobin (Hgb) due to placental
  transfusion
• ? RBC production after birth due to ?
  availability
• of extrauterine oxygen
• 2 month of age ? Hgb due to ? RBC production,
• shorter life fetal RBC
• Nadir at 7-9 wk of age Hgb 11 gr./dl

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Physiological Anemia of Infancy (contd)

• ? placental transfusion in
• placenta previa or abruptio
• multiple gestation
• cord clamping lt 30 seconds
• C-section
• Cord around neck
• 24-32 week retics are 15 of RBCs, at birth 7
• Day 7, retics ? to 1

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Postnatal changes in hemoglobin and
ared-blood-cell indices in term infants
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Anemia of Prematurity

• Premature Infant more rapid decline and lower
• nadir of Hgb than term
• 40 infants lt33 weeks show symptoms of anemia
• Epo ? rapidly, Epo levels 50 lt than adults at
• same Hgb level
• Epo ? slowly as Hgb falls in premature babies
• Epo produced in liver

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Anemia of Prematurity (contd)

• Decision to transfuse ? controversy for last
• 30 years
• Anemia ? risk of apnea and failure to thrive.
• Transfusion at predetermined Hgb level not cost
  effective and doesnt ? apnea

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Sites and Timing of Neonatal Blood Loss

• A Fetus
• 1. Internal hemorrhage
• 2. Fetomaternal Hemorrhage
• 3. Fetoplacental hemorrhage
• abruption,previa, marginal sinus
  ,or hematoma
• 4. Twin-twin transfusion chronic

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Sites and Timing of Neonatal Blood Loss (cont.)

• B Newborn
• 1. Twin-Twin transfusion acute
• 2. Umbilical-cord rupture or hematoma-normal
• or abnormal cord
• 3. Internal hemorrhage Intracranial, hepatic
  or
• splenic rupture or hematoma, adrenal
  or
• retroperitoneal hematoma. Pulmonary
  bleed
• 4. Placental trapping caesarean section, early
  
• cord clamping, precipitous delivery

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Fe Deficiency Anemia

• Most common etiology of anemia
• Lack of dietary iron
• Contributing factors in children
  Rapid growth
• 
  Insufficient Fe
• Absorption
• Blood loss
• Breast milk or formula vs. cows milk
• Diet Cereals
• Meat

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Fe Deficiency Anemia (contd)

• Lab Hemoglobin?
• MCV ?
• Serum Fe/TIBC?
• Serum Ferritin?
• Platelets frequently ?
• Trial of Fe
• Treatment Oral ferrous sulfate ? 5-6 mg/kg of
  elemental Fe x day x 3 months
• Side effects of Fe

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THROMBOPOIESIS IN FETUS AND NEWBORN
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Thrombopoiesis

• I Yolk sac phase
• small megakaryocytes by 5 week,
• platelets large and hypogranular
• II Hepatic phase
• early stage by 6 week
• Megakaryoblasts and promegakaryocytes seen
• late stage 9-11 weeks
• Megakaryocytes comparable to adult, but
  smaller

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Thrombopoiesis (contd)

• III Bone Marrow phase after 11 weeks
• from 11 to 22 stable number megakaryocytes, then
  ? 22 to
• 40 week.
• Size still small, adult size by one year of
  age.
• Newborns easily develop thrombocytopenia due to
  
• sepsis. Little is known of newborn
• megakaryocytopoietic-thrombopoietic capacity

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WELL
Large platelets Normal hemoglobin
and WBC
Small Platelets Congenital anomalies Mean
corpuscular volume
Consumption
Synthesis
Immune
Congenital
ITP 2 to
SLE, HIV Drug Induced
TAR
Wiskott-Aldrich Syndrome
X-linked Amegakaryocytic
Fanconi anemia
Maternal ITP NATP
Non-immune
2B or platelet-type vWd Hereditary
macrothrombocytopenia
Acquired Medications,Toxins,Radiation
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ILL
Fibrinogen Fibrin degradation
products Large
platelets
Small platelets HSM
Mass
Synthesis
Consumption
Microangiopathy Hemolytic-uremic
syndrome TTP
Malignancy Storage disease
Sequestration
Disseminated intravascular coagulation
Necrotizing enterocolitis
Respiratory distress Thrombosis
UAC
Sepsis
Viral infection
Hemangioma
Hypersplenism
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Thrombocytopenia

• Infant Factors
• Platelet lt 100,000/mm3 in 80 sick
  infants ?60
• known etiology
• 22 infants in NICU have ? platelets
• Approximately 25 have significant
  bleeding
• ? platelets associated with sepsis, respiratory
  distress, ? bilirubin, ventilation,
• asphyxia, meconium, hypothermia,
  pulmonary
• hypertension, polycythemia
• Sepsis ? 52-77 have ? platelets,
• may be 1st manifestation. Mean
• duration 5 days.

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CLINICAL CASES

• I Tyler is an 11- month- old boy brought to your
  office by his mother who thinks he is pale and a
  bit irritable.
• He has not had any recent illnesses and is on no
  medications.
• History of presenting complaint
• Past medical history
• Diet
• Family History
• Physical Exam

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LAB

• Hb 82 g/L
• MVC 65
• WBC 6.9 x 109/L
• Platelets 540,000 x 109/L
• Possible diagnosis
• Treatment

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CLINICAL CASES (contd)

• II Amanda is a 2-month-old girl you are seeing
  today for her lst immunization. Her mother
  reports that Amanda sleeps a lot and looks pale.
  She is growing well and breastfeeds vigorously.
• She is on no medications.
• History of presenting complaint
• Past medical history
• diet
• Family history
• Physical exam

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LAB
0

• Hb 102 g/L
• MCV 84
• WBC 8.3 x 109/L
• Platelets 240,000 x 109/L
• Possible diagnosis
• How would you manage this patient?

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Pancytopenia

• Reduction below normal values of 3 blood lines
• Leukocytes Platelets Erythrocytes
• Hypocellular Marrow Seen in
• Constitiutional (Inherited) marrow failure
  syndromes
• Acquired Aplastic Anemia
• Hypoplastic Variant of Myelodysplastic Syndromes

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Pancytopenia (cont)

• Cellular marrow seen in
• Primary bone marrow disease as Acute Leukemia,
  MDS, Myelofibrosis
• Secondary to systemic disease autoimmune disease
  (SLE), Vitamin B12 or folate deficiency, storage
  disease, metastatic solid tumors, etc.

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Constitutional (Inherited) Pancytopenia Syndromes

• Fanconi Anemia
• Shwachman-Diamond Syndrome
• Dyskeratosis Congenita
• Amegakaryocytic Thrombocytopenia
• Other Genetic Syndromes
• Down Syndrome
• Dubowitz Syndrome
• Seckel Syndrome
• Reticular Dysgenesis
• Schimke Immuno-Osseous Dysplasia
• Familial Aplastic Anemia (non-Fanconi)
• Pearson Syndrome
• Reticular Dysgenesis
• Noonan Syndrome

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Fanconi (Aplastic) Anemia

• Autosomal recessive syndrome
• Hematological findings
• Typical physical anomalies
• Abnormal chromosomal fragility

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Characteristic Physical Anomalies in Fanconi
Anemia

• Anomaly
• Skin Pigment Changes
• Short Stature
• Upper Limb Abnormalities (thumbs,hands,radi,ulnas)
  
• Hypogonadal and Genital Changes (mostly males)
• Other Skeletal Findings (head/face,neck,spine)
• Eye/lid/epicanthal fold anomalies
• Renal Malformations
• Ear Anomalies (external internal), deafness
• Hip, leg, foot, toe abnormalities
• Gastrointestional/cardiopulmonary malformations

• Approximate Frequency
• ( of Patients)
• 65
• 60
• 50
• 40
• 30
• 25
• 25
• 10
• 10
• 10

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Marrow Failure Before Age 10 Years

• Thrombocytopenia often first
• Granulocytopenia
• Macrocytic Anemia
• Severe Aplastic Anemia in Most Cases
• Increased Propensity for Cancer Carcinomas of
  Head, Neck, Carcinoma of Vulva and Anus

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Treatment

• Transfusions
• Hematolpoietic Stem Cell Transplant is only
  Curative Treatment
• Androgens Prednisone
• Prognosis Median Survival is gt30 years of Age