Download Anemia

Anemias in children
Anemia…
… abnormal low hemoglobin, hematocrit or
RBC count, lower than the age-adjusted
reference range for healthy children.
Anemia…
… abnormal low hemoglobin, hematocrit or
RBC count, lower than the age-adjusted
reference range for healthy children.
Etiologic classification
I






Impaired red cell formation
A/ Deficiency
Decreased dietary intake
Increased demand
Decreased absorption
Increased loss
B/ Bone marrow failure
Failure of a single or all cell lines
Infiltration
C/Dyshematopoietic anemia
II Blood loss
III Hemolytic anemia


Corpuscular (membrane, enzymatic or hemoglobine defects)
Extracorpuscular (immune, idiopathic)
Diagnosis of Anemia



detailed history
careful physical
examination
peripheral blood smear
 red cell morphology
 MCV
 RDW (red cell
distribution width)
 WBC and platelet
morphology

Additionally:
-bone marrow
evaluation
-additional
testing
History
- Diet (iron , folate, vitB12 intake,
onset of hemolysis
after certain foods –e.g.,fava beans)
- family history (transfusion requirements of
relatives, splenectomy, gallblader disease)
- environmental exposures (lead poissoning)
- symptoms (headache, exertion dyspnea,
fatigue, dizziness, weakness, mood or sleep
disturbances, tinnitis)
- melena, hematemesis, abdominal painchronic blood loss
Physical Examination







Pallor

(skin, oral mucosa, nail
beds)

Jaundice -hemolysis
tachycardia
tachypnea
orthostatic hypotension
venous hum
systolic ejection
murmur





peripheral edema?
Splenomegaly?
Hepatomegaly?
Glossitis?
gingival
pigmentation?
Adenopathy?
Facial, extremity
examination
Peripheral Blood Components
important! Different values dependent on age!







RBC
Hgb
HCT
MCV – 80 – 100 fl/L (a calculated value)
MCH
RDW
Reticulocyte Count
MCV for Characterize Anemia
(>85fl)
*Macrocytic
Low(<70 fl)
*Hypochromic/Microcytic 

-Iron deficiency anemia
-Thalassemia
-Sideroblastic anemia
-Chronic infection
-Lead poisoning
-Inborn errors of Fe metabolism
-Severe malnutrition
-Copper deficiency






Normal newborn
Increased erythropoesis
Post splenectomy
Liver disease
Aplastic anemia
Megaloblastic anemia
Down S.
Obstructive jaundice

Normocytic





Acute blood loss
Infection
Renal failure
Connective tissue
disorders
Liver disease





Disseminated
malignancy
Early iron deficiency
Aplastic anemia
Bone marrow
infiltration
Dyserythropoietic
anemia
Megaloblastic anemia




Presence the megaloblasts in the bone marrow and macrocytes
in the blood
In > 95% occurs as a result of folate and vitamin B12
deficiency
Deficiencies of ascorbic acid, tocopherol, thiamine may be
related to megaloblastic anemia
Dietary vitamin B12 (cobalamine) is required from animal
sources (meat and milk)
Causes of vitamin B12 deficiency
I Inadequate dietary intake (<2mg/day) –malnutrition, veganism,
maternal deficiency
II Defective vitamin B12 absorption
 Failure to secrete intrinsic factor
 Failure to absorption in small intestine
III Defective vitamin B12 transport
IV Disorders of vitamin B12 metabolism (congenital, acquired)
Folic acid deficiency





One of the most common micronutrient deficiences in the
word
(next to iron deficiency)
Component of malnutrition and starvation
Women are more frequently affected than men
Folate sufficiency prevents neural tube defects
Low mean daily folate intake is associated with twofold
increased risk for preterm delivery and low infant birth weight
Causes of folic acid deficiency





Inadequate intake (method of cooking, special diet, goat’ milk)
Defective absorption (congenital or acquired)
Increased requirements (rapid growth, chronic hemolytic
anemia, dyserythropoietic anemias, malignant disease,
hypermetabolic state, cirrosis, post –BMT)
Disorders in folic acid metabolism (congenital, acquired)
Increased excretion
Clinical features of cobalamine and folate
deficiency



Insidious onset: pallor, lethargy, fatigability, anorexia, sore red
tongue and glossitis, diarrhea
History: similarly affected sibling, maternal vitamin B12
deficiency or poor maternal diet
Vitamin B12 deficiency: signs of neurodevelopmental delay,
apathy, weakness, irrability, athetoid movements, hypotonia,
peripheral neuropathy, spastic paresis
Megaloblastic Anemias:
Clinical Findings
•Anemia
is slow to
develop
•Fatigue
• Weakness
• Yellow color
•Weight loss
•Glossitis
Megaloblastic Anemia:
Lab Features: Hematology

Macrocytic, normochromic anemia




Increased MCH: due to large cell volume
Normal MCHC
RBC, HGB, Hct decreased
Granulocytes and Thrombocytes are
affected as well.


Granulocytes are hypersegmented
Megakaryoctyes are abnormal resulting in thrombocytopenia
Megaloblastic Anemia:
Lab Features: Peripheral blood

Triad of oval macrocytes,
Howell-Jolly bodies and
hypersegmented neutrophils

Anisocytosis, Poikilocytosis

RBC’s are fragile, lifespan is
shortened and many die in
the bone marrow which
causes ↑ LDH
Megaloblastic Anemia:
Lab Features: Misc
Bone marrow
 Hypercellular with
megaloblastic erythroid
precursors
 M:E ratio decreased
Chemistries
 Vitamin B12
 Folate
 Methylmalonic acid
(MMA)
 Homocysteine
 Lactic
dehydrogenase(LDH)
Diagnosis








Red cell changes: Hgb usually reduced,
MCV increased to levels 110 – 140fl., MCHC normal,
in blood smear many macrocytes and macro-ovalocytes, anisocytosis,
poikilocytosis, presence of Cabot rings, Howell-Jolly bodies, punctate
basophilia
White blood cell count reduced to 1500 – 4000/mm3,
neutrophils show hypersegmentation (>5 lobes)
Platelets count moderately reduced (50,000 – 180,000/mm3)
Bone marrow: megaloblastic appearance
Serum vitamin B12 values lowered (normal 200 – 800 pg/ml)
Serum and red cell folate levels – wide variation in normal range;
less than 3 ng/ml -very low, 3-5 ng/ml –low, >5-6 ng/ml normal,
in red cell:74-640 ng/ml
Schilling urinary excretion test – measurement of intrinsic factor
availability and absorption of vitamin B12
Treatment
Vitamin B12 deficiency
Prevention in cases of risk of vitamin B12 deficiency
Treatment 25 – 100µg vitamin B12
Folic acid deficiency
Correction of the foliate deficiency (100-200µg/day)
Treatment of the underlying causative disorder
Improvement of the diet to increase folate intake
Megaloblastic Anemia: Causes of





Vitamin B 12 deficiency
Folate deficiency
Drugs
Myelodysplastic syndromes
Acute leukemia
Megaloblastic Anemias:
Deficiency of Vitamin B12

Vitamin B12 (cyanocobalamin) deficiency
1. Inadequate dietary intake
a. B12 is found in food of animal origin: red
meat, fish, poultry, eggs, dairy products
Megaloblastic Anemias:
Deficiency of Vitamin B12
2.
Malabsorption
a.
Pernicious anemia






Caused by gastric parietal cell atrophy which causes decreased
secretion of intrinsic factor (IF). IF is necessary for B12
absorption.
Atrophy due to immune destruction of the acid-secreting portion of
the gastric mucosa
Onset is usually after age 40, primarily women
Affects people of Northern European backgrounds
Neurologic problems
Schilling test used for diagnosis
Schilling test


Establishes the cause of
vitamin B12 deficiency
Test performed in two
parts
 If parts one & two
abnormal: Pernicious
anemia
 If part one only
abnormal:
malabsorption
B12 Malabsorption causes (con’t)
Gastrectomy
Blind loop syndrome
c.
d.

bacteria use up the B12
Fish tapeworm= Diphyllobothrium latum
d.

completes for B12
Other Causes for B12 Deficiency
3.
Drugs
a.
b.
c.
Alcohol
Nitrous oxide
Antitubercular drug
Megaloblastic Anemia:
Folic Acid (Folate) deficiency
1.
Inadequate dietary intake
a. Poverty
b. Old age
c. Alcoholism
Megaloblastic Anemia:
Folic Acid (Folate) deficiency
2.
Malabsorption
a. Ileitis/Crohn’s disease
b. Tropical sprue
c. Blind loop syndrome
d.
Nontropical sprue
a.
b.
Gluten-sensitive enteropathy
Childhood celiac disease
Megaloblastic Anemia:
Folic Acid (Folate) deficiency
3.
Increased requirement
a. Pregnancy
a. There is increased demand during pregnancy and
should be supplemented prior to and during
pregnancy. Deficiency during pregnancy can
cause neural tube defects in utero.
b. Infancy
c. Hematologic diseases that involve rapid cellular
proliferation such as sickle cell anemia
Hemoglobin values vary with age
Age
Hb (gm/dL)
Newborn
(cord blood)
13.8-20.0
MCV= 96 -116
Reticulocytes 37%
Infancy
2-3 months
3-6 months
6-12 months
9.0 (term)
8.5 (low birth wt.)
9.5
10.0
Child
12-24 months
> 24 months
10.5
11.5
Adolescence
> 13 years
12.0 (female)
13.5 (male)
Differential Diagnosis of Anemia
•Divide into groups by size of cell
(MCV) Macrocytic
Microcytic
Normocytic
Fe-def
Acute blood loss
Newborn
Thalassemia
Liver disease
Liver disease
Sideroblastic
Renal disease
Hypothyroidism
Lead toxicity
Infiltrated marrow
Splenectomy
Hgb
E TEC
Trisomy 21
Inborn errors
Connective
tissue
Reticulocytosis
Copper def.
Aplastic Anemia
Anemia/MDS
Aplastic
Atransferrinemia
Vit B12/Folat
Differential Diagnosis of Anemia
•
Consider increased destruction versus decreased production based on reticulocyte count
Production
Dietary(Fe,B12,Folate)
Aplastic Anemia
Diamond-Blackfan TEC
Bone Marrow infiltrate
Destruction
Hemoglobin
Enzyme defects
Membrane defects
Immune-mediated
19 mo old male noted by his grandmother to be pale and fussy.
Described as very picky, his diet is mainly string cheese,
mac & cheese and milk. The child appears in no distress.
He is slightly tachycardic with normal heart rhythm, no gallop, +systolic
murmur, normal BP and good peripheral perfusion. CBC shows Hb=5.0
gm/dl,
MCV 52fL, retic 1.6%.
What is the most appropriate clinical management?
1) Refer immediately to the closest hospital for 10cc/kg PRBC transfusion.
2) Schedule a slow transfusion with 5cc/kg of PRBC then start supplementation with
oral iron.
3) Start the patient on a daily children’s chewable vitamin with Fe.
4) Obtain nutrition consult and start oral Fe at 3-6 mg/kg elemental Fe daily.
Which of the following sets of labs are consistent with
iron deficiency anemia?
1) ↑ RDW, ↓ RBC#, ↑ MCV
2) Normal RDW, ↑ RBC#, ↓ MCV
3) ↑ RDW, ↓ RBC#, ↓ MCV
Thal trait vs. Fe-deficiency
•Remember, in thalassemia trait, all red cells are very small (↓ ↓
MCV), but they’re all the same size (nl RDW), and there is no
production problem (nl to ↑ RBC). There is marked discrepancy
between Hgb value and MCV, whereas in Fe-def, these two
values tend to go down at a similar rate.