Pediatric Hematology pdf - D. Ali

L1 Pediatric D. Ali

Blood elements

Blood consist of 3 elements , erythrocytes ( red cells ) , leukocytes ( white cells ) & thrombocytes
( platelets ) . All are suspended in the plasma

Site of blood cell formation

  1st 2 month ( intrauterine ) : in the yolk sack
  2-7 month ( intrauterine ) : in the liver
  Bone marrow start at the 5th month ( intrauterine ) - take over after birth

Erythropoiesis

Hemoglobin (Hb) composition

Hb Molecule Is Composed Of 4 Heme Groups (Containing Ferrous Iron) Attached To 4
polypeptide chains which define the type Of Hb

Fetal Hemoglobin

(Hb F )

Major adult Hb

(Hb A )

Minor adult

( Hb A2 )

Consists of

At birth

70% of Hb

About 30%

Less than 1%

6-12m

Below 2%

Above 95%

Anemia

Definition:

decrease of Hemoglobin or hematocrit concentration below the normal value for age.

Range

•  At birth 15-20gm /dl
•  2-3 month : decrease to 10 gm/dl
•  Rise gradually with age to 15 gm at 15years

Causes (classification) of Anemia

1- Decreased RBCs production

2-Increased RBCs destruction

1. Hemolysis

2. Hypersplenism : leading to pancytopenia

3-Blood loss ( haemorrhagic anemia

)

 Acute : trauma ,accidents , surgery - varices - operative ( circumcision in hemophilics)
 Chronic : feto - maternal transfusion - ankylostoma - bilhariziasis - meckel's

diverticulum

Dyshematopoietic Anemia

- Iron deficiency Anemia
- Folic acid & vitamin B12

(megaloblastic Anemia )

- Vitamin

and

protein

deficiency

- CU& vitamin B6 deficiency

Bone marrow failure
A- Pure red cell aplasia

- Inherited : shwachman – diamond syndrome

AR – associated exocrine pancreatic failure

- Acquired with ( parvo V. B19)

B- Aplastic Anemia : ( pancytopenia )

- Congenital :e.g. fanconi Anemia
- Acquired : idiopathic or secondary to infections ( hepatitis ) – toxins

(insecticide)

- – irradiation

C- Infiltration of bone marrow malignant cell e.g. Leukemia or metabolic cells as

Gaucher cells

A. Corpuscular defects
( hereditary )

B. Extra Corpuscular ( Extrinsic)

( Acquired )

a-  Membrane defect :
-  Spherocytosis
-  Elliptocytosis
b- Enzyme defect :
-  G6PD deficiency (A )
-  Pyruvate kinase def.
c-  Hemoglobin defect :
-  Quantitative : thalassemia
-  Qualitative  :  sickle  cell

Anemia

Immunologic disorders : ( coombs + ve )

Non
Immunologic
Disorders

 Rh & ABO incompatibility

 Autoimmune haemolytic anemia
- Idiopathic
- Infections (e.g.EBV,CMV & Mycoplasma pneumonia )
- Drug – induced (e.g. methyldopa, penicillin )
- Collagen vascular diseases ( SLE)

 Sepsis
 Malaria
 Wilson Disease
 Artificial Valve
 Dic
 Haemolytic

Uremic Syndrome

Iron metabolism

Dietary requirements

1 mg of iron must be absorbed / day. (Intake of 10mg of iron / day) . Iron is absorbed 2-3 times
more from human milk than from cow's milk

Absorption

Luminal border of duodenal mucosa: iron is absorbed in the ferrous form .

Inside duodenal mucosa : it is oxidized to the ferric form and becomes attached to an iron free
protein called apoferritin , to form ferritin . When the available apoferritin is fully saturated with
iron absorption by the duodenal mucosa stops .

Distribution

  In the plasma : combined with transferrin as ferric iron .
  The iron binding capacity = 250-350mg / 100 ml .
  Storage : iron is then delivered to the liver , spleen and bone marrow .

Iron deficiency Anemia

Incidence

: the most common cause of anemia in infancy

Causes:

A. Diminished stores :

 Anemic mother with deficient iron supplementation
 Premature and twins

B. Deficient dietary iron :

  Prolonged breast feeding
  Cow milk
  Protein energy malnutrition

C.  Diminished absorption : chronic diarrhea - malabsorption
D.  Blood loss : chronic hemorrhage - ankylostoma - schistosomiasis - cow milk allergy
E.  Increased requirements : in ( adolescent specially girls - acute hemorrhage )

Clinical features:

 Onset : above 6 month ( more common between 9-24month )
 General symptoms of anemia : pallor ( nail bed - palm - lids ) - tachycardia - murmurs

heart failure - dyspnea - easy fatigability

  Atrophic glossitis
  Poor appetite
  Poor concentration and behavioral abnormalities
  Spooning of the nail
  Pica : ( geophagia ) eating unusual substances as dirt and mud
  Palpable spleen in 15% of causes

Investigation:

Blood pictures:

Low Hb . Microcytic hypochromic anemia: MCHC < normal & microcytic MCV < normal]

Reticulocyte count is normal, it show mild increase with therapy.

Blood chemistry:

Low serum iron < 50mcg % (normal 90-150micg/dl)

Low serum ferritin < 10ng (normal 30 - 150 ng )

Increased iron binding capacity (normal: 250 - 350 micg / dl )

Detect the cause

Stool analysis: ankylostoma - blood in stool - bithariziasis

Endoscopy:

to exclude peptic ulcer.

D.D from other causes of hypochromic microcytic anemia:

Prevention:

1-  Adequate supply of iron to pregnant female
2-  Making powdered formula well - fortified with iron
3-  Prophylactic iron therapy to premature
4-  Proper weaning by supplying iron containing foods
5-  Treatment of cause

Treatment:

Iron therapy:

Oral therapy: ferrous sulfate or gluconate 6 mg / kg / day / 3 doses in between meals for 2 month.
(new preparations ( no teeth stain - minimal GIT upset ) , e.g. sodium iron edetate .

Parenteral therapy: I.M. iron dextran dose : 50 - 100 mg daily for 5 days I.V. iron hydroxide in
severe cases

Diet: rich in iron ( meat , liver , green vegetables ) and vitamin C .

Packed RBCs transfusion

Treatment of cause

Chronic Hemolytic Anemia

Pathophysiology:

 In Hemolysis : RBC life span shorten ( 120 day down to few days )
 Bone marrow compensate to 8 fold ( more rapid Hemolysis will manifest)

BY 1

DAY : reduced irritability , improved appetite

BY 2

DAY : erythroid hyperplasia in bone marrow , show erythroid hyperplasia

BY 3

DAY : reticulocytosis peaking at 5-7 days ( good therapeutic test )

BY 1

MONTH : elevated hemoglobin 1/4 gm / dl / day

4 – 6 weeks : increased stores

Organomgaly and disfigurement:

Hepatosplenomegaly with minimal lymphadenopathy :

1-  Destruction of abnormal RBCs .
2-  Formation of new RBCs ( extra medullary hematopoiesis )
3-  Deposition of iron overloads ( hemosidrosis )

N.B. : splenomegaly will result in Hypersplenism with more severe anemia and
pancytopenia

Macrocephaly:

of face due to compensatory bone marrow action .

Prominent zygoma , forehead , maxilla with [ depressed nasal bridge - prominent upper central
incisor - separation of teeth ]

Dilated heart & heart failure

: due to tachycardia - relative hypoxia ( anemia ) cardiomyopathy

due to hemosidrosis

Investigations:

  To prove anemia : CBC shows low Hemoglobin
  To prove Hemolysis :
-  Blood film : reticulocytosis
-  Blood chemistry : elevated serum indirect bilirubin , serum iron , serum ferritin , decreased

iron binding capacity

- Increased urinary urobilinogen
- X ray finding : of poor value : bone marrow expansion ( wide diploid space of the skull -

rarefaction of the other table -increased trabecular pattern

Clinical picture :-

Clinical picture of anemia in general

Anemia usually need frequent blood transfusion

Clinical picture of Hemolysis :

Jaundice – attacks of red urine ( hemoglobinuria ) – dark urine on standing – dark stool – bronzed discoloration ( need years )

Complications:

 Complication of long term blood transfusion :

o  Hemosidrosis
o  10% of causes show antibodies with difficulty to find compatible blood
o  Infection ( HBV - HCV - HIV - Malaria )
o  Complication of venous access ( infection and bleeding )

  Anemic heart failure :
  Gall bladder stones :
  Crises : aplastic , hemolytic , sequestration - ( VOC in SCA )
  Deposition of iron in tissues ( hemosidrosis ):

Each 500ml of blood deliver 200mg of iron

o  Endocrinal disturbances : delayed puberty - pituitary dysfunction diabetes mellitus
o  Liver cirrhosis and liver failure
o  Pulmonary hemosidrosis
o  Cardiomyopathy
o  Arthropathy
o  Neuropathy

  Easy fracture of bones
  Growth retardation and delayed puberty
  Hypersplenism ( mainly in thalassemia mainly )
  Autosplenectomy in SCA

Thalassemia

Incidence

: β - thalassemia is the commonest chronic hemolytic anemia common in the

Mediterranean area , while a - thalassemia is rare .

Inheritance

: autosomal recessive disease

Genetics

-  Defective synthesis of one of the globin chains ( the gene is absent or non - functioning ) :
o  If the defect in ɑ chain production : a thalassemia
o  If the defect in β chain production : β thalassemia
-  β thalassemia : 2 genes on chromosome 11
o  2 gene mutation ( homozygous ) : thalassemia major ( Cooley's anemia )
o  1 gene mutation ( heterozygous ) : thalassemia minor
o  Thalassemia intermedia : moderate severity

Beta thalassemia major (Cooley’s anemia)

Pathogenesis

The bodies try to switch to Hb A at the age of 3 - 5 months but the gene of B chain is defective (
production of restricted amount of Hb A )

Then the body try to reproduce Hb F but also its production will be defective free ɑ chain become
insoluble and precipitate inside RBC ( Hemolysis )

Clinical picture

 onset : by 2

half of the 1

year

 The Course is sever with frequent blood transfusion
 most liable for early complications and early development of Hypersplenism

Investigations:

Prove anemia & Hemolysis blood film : microcytosis - anisocytosis - target cells - poikilocytosis .

Hemoglobin electrophoresis: in the affected child : Hb F is markedly elevated (90% ) - reduced
Hb A parents : increased of Hb A2 > 4 % ( normal : 3 % )

Differential diagnosis

From other causes of chronic hemolytic anemia

Thalassemia minor

 Most cases are asymptomatic
 The condition is suspected when a patient with microcytic hypochromic anemia Fails

to respond to iron therapy

 Blood picture : microcytic hypochromic anemia - obvious signs of hemolysis
 Hemoglobin electrophoresis : increased Hb A2

Prevention:

Genetic counseling, carrier detecting & prenatal diagnosis

Treatment:

1. Supportive treatment : restrict iron in diet / folic acid 1mg / day . hepatitis B vaccine .

calcium and vitamin D

2. Repeated packed RBCs transfusions :

 10-15 ml /kg every month to keep Hb level at 10-12 mg /dl ( hyper transfusion )
 Value : good activity - better growth - reduce Organomgaly & disfigurement

3. Iron chelating agents :

 Desferroxamine ( desferal ) : 20 - 40 mg / kg by s.c. pump over 10 hours , 5days /

week .

 Deferiprone : oral chelating agent ( 100 mg / day divided by 3 times )
 Deferasirox : oral - effective ( 10 - 20 /kg / day )

4. Spleneectomy : indications : huge splenomegaly or Hypersplenism ( avoid before the age

of 4 years )

Splenectomy care:

-  Before Splenectomy : vaccination ( pneumococci - meningococci - H . influenza )
-  After Splenectomy : long acting penicillin prophylaxis till the age of 18 years .
5.  Bone marrow transplantation :

- Prepared from bone marrow from a HLA match
- It is curative ( best below 3 years )

6. Gene therapy : introduction of a functioning gene ( under trials )
7. Induction of fetal Hemoglobin synthesis :

- Hydroxyurea can stimulate Hb F production

Treatment of complications:

  Gall bladder stone : cholecystectomy
  Diabetes : insulin therapy
  Short stature : growth hormone

Mubark A. Wilkins