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Dr.A.J.Chitkara & Dr. Neeraj Adlakha Consultant Pediatricians Sarvodaya Hospital & Max Hospital, Pitampura

Anemia is a decrease in hemoglobin concentration (or hematocrit) of more than two SD below the mean. The Hb level varies with age, a high Hb in neonates falling to a low level at 2-3 months of age (physiological anemia of infancy) & then rising steadily till puberty. The Hb level should always therefore be interpreted in the context of age & sex of the patient. Males after puberty have 20% higher Hb than females. Another noteworthy feature while evaluating unexplained mild anemia in relatively normal children, is that 2.5% of general population may have a lower Hb/ Hct than normal for that age. Anemia becomes clinically relevant when low Hb results in decreased oxygen carrying capacity of blood.

The pathophysiological mechanisms causing anemia are:

• Acute blood loss
• Impaired production of RBC
• Increased destruction of RBC

History

Historical clues in evaluation of Anemia

A careful evaluation of medical history often gives vital clues to the cause of anemia. The acuity of anemia, association with other symptoms & history of any chronic illness are important. Some important points are summarized in the Table

Physical Examination

• General appearance of child & assessment of growth parameters helps decide the acuity or chronicity of anemia & other associated illnesses.
• Look for signs of trauma
• Presence of petecie, bruising & ecchymosis
• Lymphadenopathy, Hepato-spleenomegaly & abdominal mass.
• Prominent cheek bones, frontal bossing indicates hemolytic anemia
• Associated congenital malformations- Fanconi anemia.
• Tell tale signs of any chronic illness e.g. hypertension, short stature, arthritis, cluubing, cyanosis etc.

Laboratory Evaluation

The three most important investigations to be carried out in a child with anemia are:
Hemoglobin
Complete blood count
§ RBC
§ WBC
§ Platelets

• Peripheral smear
  Anemia as a cause of pallor occurs when Hb falls below 8-9 gm%. False anemia as a result of laboratory error, sampling error must be considered if laboratory & clinical findings do not correlate. Capillary blood sample often leads to error.
• Most laboratories perform test on automated counters which measures Hb (gm/l), RBC count (cells/cmm), MCV in femtolitres (fl). While MCH & MCHC are derived parameters.
• MCV or mean corpuscular volume is an important parameter to classify anemia. The minimum value at any age is represented by 70 plus age in years & reaches adult level of 80-100fl by puberty.
• Reticulocyte count expressed as percentage of RBC is another important marker used to differentiate anemia. Normal reticulocyte count is less than 2 %. Corrected reticulocyte count reflects bone marrow activity more appropriately and is derived from the formula: corrected reticulocyte count= reticulocyte count × Hb or pcv of patient / Hb or pcv at that age.
• RDW or red cell distribution width is a measure of variability of RBC size (anisocytosis). It is calculated from histograms. The normal range is 11.5 to 14.5. It increases if variation of RBC size is high.
• Normochromia and hypochromia indicate normal or decreased RBC hemoglobin content respectively and is also used to classify anemia. Hyperchromia does not exist.
• Finally evaluation of WBC & platelet count and morphology reflects any associated abnormality of these cell lines which may coexist & point to the cause of anemia.

The history & clinical examination often prove anemia to exist and the underlying cause. The above laboratory indices when applied in combination, characterize the type of anemia & further confirm the etiological diagnosis. A very easy & comprehensive flow chart using the above parameters is outlined below :
The detailed description of each anemia is beyond the scope of this article, but a few common conditions encountered in daily clinical practice are discussed briefly with the salient diagnostic features.

Microcytic Anemia

The most commonly detected anemia are the microcytic, hypochromic anemia.

Iron deficiency is the most prevalent form and preventable form of microcytic anemia. Prevalence rate may vary from 30% to 70%. Low birth weight, malnutrition, occult bleeding from GI Tract due to polyp, ulcer, diverticulum, cow milk allergy & hook worm infestation and chronic diarrhea cause iron deficiency. Non hematological consequences include impaired cognitive development, epithelial abnormalities, exercise intolerance, behavioral abnormalities & impaired collagen synthesis. Thalessemia (Cooley’s anemia) is an inherited disorder resulting in deletion of either ? or ß globin chains & accordingly classified as ? or ß thalessemia. It is a hemolytic anemia presenting between 6-12 months of age with anemia & hepato-spleenomegaly because of ineffective erythropoesis due to abnormal hemoglobin. It is characterised by low MCV (microcytosis), normal RDW, hypochromia & target cells. Differentiation from iron deficiency is seldom difficult except in minor or intermediate severity thalessemia.

Lead intoxication & some anemia of chronic infections are microcytic & easily diagnosed because of other associated clinical findings. The following table however lists a few laboratory tests used to clinch the specific diagnosis.

Classification And Hematological Features Of Principal Forms Of Thalassemia

Type of Globin-gene Hematological Clinical Hemoglobin

thallasemia expression features expression findings

Hemolytic Anemias Other Than Thalassemia

• Pallor
• icterus
• Spleenomegaly
• Gallstones
• Positive family history
• ? reticulocyte count
• ? RDW
• Abnormal RBC morphology
• ?LDH level

The salient features of these hemolytic conditions are briefly summarized.

Internsic Defects

Hemoglobinopathies

Sickle cell anemia

• Central African, Central Indian desent
• Autosomal recessive disorder
• Amino acid substitution at no 6 position ,valine for Glutamic acid
• Onset at 4 to 6 month of age
• Variants include SS, Strait, SCdisease, Sß thallesemia
• Cinical features include:-
  § -Aplastic crisis
  § -Sequestration crisis
  § -Hemolytic crisis
  § -Vasoocculsive crisis
  § -Dactilitis
  § -Acute chest syndrome

Membrane Defects

Thalessemia : already described

Hereditary spherocytosis

• Autosomal dominant
• Defect in membrane protein spectrin/ ankyrin
• Presents as hemolytic disease in newborns or during childhood as pallor jaundice ,fatigue
• ? osmotic fragility
• Negative coombs test
• About 20% spherocytes on smear examination

Hereditary elliptocytosis :

• Autosomal dominant
• Defect in membrane protein 4.1,Glycophorin C
• Usually presents as chronic hemolysis
• Elliptocytes on blood film examination
• ?Thermal instability

Hereditory stomatocytosis :

• Autosomal dominant
• Defect in membrane protein 7.2 leading to ? Permeability to Na/K
• RBC are cup shaped
• Presents as hemolytic anemia in infancy
• Increased tendency towards in situ thrombosis

Emzyme Defects

G6PD deficiency :

• X linked recessive so only in males except lysonisation
• May present as acute episodic hemolysis or chronic hemolytic anemia
• On peripheral film large no of bite cells seen
• Glutathione present in RBC is responsible for neutralizing agents that oxidize Hb or RBC membrane .the enzyme G6PD maintains this glutathione in reduced state necessary for its action
• Drugs which can cause hemolysis are Antimalarials, nitrofurantion, nalidixic acid, chloramphenicol, Vit K analogues
• Hemolysis can also be precipitated by viral infections, diabetic ketoacidosis

Pyruvate kinase deficiency :

§ Autosomal recessive
§ Presents as chronic hemolytic anemia or severe neonatal hemolytic anemia
§ Necessary for ATP generation, the lack of which leads to increase permeability leading to depletion of K and water
§ Blood film shows speculated RBC
§ Autohemolysis is markedly increased

Extrinic Defects

• Autoimmune hemolytic anemia:
• Warm antibody type Cold antibody type
• IgG subclass IgM subclass
• Primary(idiopathic) Primary(idiopathic)
• Secondary Secondary
• Lymphoproliferayive disorder Lymphoproliferative dis
• Connective tissue dis(SLE) Infection(Mycoplasma,EBV)
• Nonlymphoid neoplasms Paroxysmal cold hem-gl-urea
• Chronic inflammatory dis(SLE) Idiopathic
• Drugs(a methyl dopa,quinidine) Cong or Tertiary syphilis
• Viral syndromes
• Due to other causes
• Thermal injury
• Liver disease
• Fragmented hemolysis
• Toxins and venoms
• Wilson disease

Macrocytic Anemia

Vitamin B12 & Folate deficiency occur in children of exclusively breast fed children of strict vegetarian mothers and those fed with Goat’s milk respectively. Malnutrion & malabsorption syndromes are other causative factors. Macrocytic RBC, hypersegmented neutrophils & occasionally pancytopenia in severe cases are the hallmarks. Congenital hypoplastic anemia ( Diamond Blackfan anemia) & Fanconi anemia are other macrocytic anemias due to underproduction in bone marrow.

Anemia of under production :

Management

The treatment of anemia depends on the cause. Deficiency anemia can be effectively treated by therapeutic doses of the deficient mineral or vitamins. Aplasia responds to anabolic steroids and or erythropoietin. Anemia associated with other systemic illnesses respond after treating the underlying disease. The inherited hemolytic anemias require repeated blood transfusion with chelation therapy for the ensuing iron overload. Blood transfusion should be reserved for severe anemia and is decided on individual merits.