Dr. Monika Nema

MICROCYTIC ANEMIA

Presented by- Dr. Monika Nema

Dr. Monika Nema

WHAT IS ANEMIA Anemia is the collection of signs and

symptoms of reduced oxygen delivery to tissues as a result of a reduction in the number of red cells and/or reduction in blood concentration of hemoglobin below the level that is expected for healthy person of same age and sex.

Dr. Monika Nema

The world health organization (WHO) has defined anemia as Hb<13.0 g/dl for men and <12g/dl for women.

Dr. Monika Nema

Hb ( g/dl ) Ht(%) MCV (fl)

Adult men 13-17 39-49 80-100

Adult women

12-15 33-43 80-100

Children 6-12 yr

11.5-12.5 37-46 77-95

6m-6yr 11-14 36-42 74-87

2m-6m 9.5-14 32-42 76-84

Dr. Monika Nema

ANEMIA Most common hematologic disorder by

far It is a clinical sign of disease It is not a single disease by itself.

Dr. Monika Nema

ERYTHROCYTES PARAMETERS

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MEAN CORPUSCULAR VOLUME

Average volume of a single red cell. Normal : 83-101 femtolitre Calculated as MCV= Packed cell volume x 10 Red cell count

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MEAN CORPUSCULAR HAEMOGLOBIN Average amount of haemoglobin in each

red cells. Normal: 27-32 picogram. MCH= Hemoglobin concentration x 10 Red cell count

Dr. Monika Nema

MEAN CORPUSCULAR HAEMOGLOBIN CONCENTRATION Represents the average concentration of

haemoglobin in a given volume of packed cells.

Normal : 31.5-34.5 g/dl. MCHC= Hemoglobin concentration x

100 Packed cell volume

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RED CELL DISTRIBUTION WIDTH It is a measure of degree of variation in

red cell size(anisocytosis) in a blood sample.

Normal : As coefficient of variation(CV)- 11.6-14

% As Standard deviation(SD) – 39-46%

Dr. Monika Nema

Dr. Monika Nema

MORPHOLOGIC CLASSIFICATION OF ANEMIA Normocytic Normochromic

Microcytic Hypochromic

Macrocytic

Dr. Monika Nema

MICROCYTIC ANEMIA

Dr. Monika Nema

CASE A patient presented with fatigue,

shortness of breath, weakness, irritability, reduced work concentration to the physician.

Doctor examined and found pallor. He simply ordered a complete blood

count.

Dr. Monika Nema

Dr. Monika Nema

MICROCYTIC ANEMIA

When the average cell size (MCV) is reduced, the anemia is classified as MICROCYTIC ANEMIA.

Usually associated with hypochromia

It is very common in all age groups.

Dr. Monika Nema

Dr. Monika Nema

MICROCYTIC HYPOCHROMIC PICTURE

Dr. Monika Nema

PATHOGENIC CLASSIFICATION OF MICROCYTIC ANEMIA Disorders of iron metabolism - Iron deficiency anemia. - Anemia of chronic disorder.

Disorder of globin synthesis - Alpha and Beta Thalassemia.

Dr. Monika Nema

PATHOGENIC CLASSIFICATION OF MICROCYTIC ANEMIA Sideroblastic anemia - Hereditary. - Acquired.

- Reversible Acquired.

Lead Intoxication.

Dr. Monika Nema

CLINICAL FEATURES

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•Shortness of breath

•Palpitation

•Decreased work or exercise tolerance•Fatigue•Weakness

Dr. Monika Nema

IRON DEFICIENCY ANEMIAPica ( Abnormal eating pattern ) is striking symptom of iron deficiency anemia.

Dr. Monika Nema

IRON DEFICIENCY ANEMIA Iron deficiency usually arises from

chronic blood loss. The major cause in younger women is

menstruation. In non menstruating women and in

men, the most common source is gastrointestinal hemorrhage.

(esophageal varices,hiatus hernia, peptic ulcer,gastritis,neoplasm ,hook worm infestation)

Dr. Monika Nema

CAUSES OF IRON DEFICIENCY ANEMIA

Inadequate dietary intake of iron Defective absorption of iron (Achlorhydriya,

Gastric surgery, Celiac disease, Duodenal bypass, Drugs, Tannins, Phytate, Bran)

Dr. Monika Nema

Increased requirements of iron

(Pregnancy, Infancy, Lactation) Inadequate presentation to erythroid precursors

(Atransferrinemia, Atransferrin receptor antibodies)

Abnormal iron balance

(Aceruloplasminemia, Autosomal dominent hemochromatosis due to mutation in ferroportin)

Dr. Monika Nema

THALASSEMIA Is an inherited autosomal recessive blood

disease which results in reduced synthesis or no synthesis of one of the globin chains that make up hemoglobin causing the formation of abnormal hemoglobin molecules leading to anemia.

Thalassemia is a quantitative problem.

Dr. Monika Nema

Thalassemia minor patients are usually asymptomatic. Diagnosis is made through evaluation of positive family history.

Dr. Monika Nema

SIDEROBLASTIC ANEMIA These are group of disorders of

varying aetiology in which marrow shows marked dyserythropoiesis & intra mitochondrial accumulation of Fe in erythroid precursors

Dr. Monika Nema

In sideroblastic anemia, majority of patient exhibits manifestations of iron overload.

Abnormal glucose tolerance, cardiac arrhythmia and congestive heart failure can occur.

Dr. Monika Nema

In case of Lead poisoning, There can be occupational history of

inhaling fumes in industry. Ingestion of lead based paint chips by

children. Ingestion of contaminated herbs and

food supplements. Gasoline sniffing in addicted person.

Dr. Monika Nema

CAUSES OF ANEMIA OF CHRONIC DISEASEA. Chronic inflammation Rheumatoid arthritis systemic lupus erythematosis Crohn’s diseaseB. Chronic infection Tuberculosis Urinary tract disease HIV infection Bacterial endocarditis pneumoniaC. Neoplasm Carcinoma Lymphoma Myeloma

Dr. Monika Nema

PATHOGENESIS OF ANEMIA OF CHRONIC DISEASE Anemia is related to decrease in release of iron

from macrophage to plasma Reduced RBC lifespan Inadequate erythropoietin response to anemia,

caused by effects of cytokine such IL-1, TNF on erythropoiesis

Hepcidin released by the liver in response to inflammation. Hepcidin functions to regulate (inhibit) iron transport

across the gut mucosa, thereby preventing excess iron absorption and maintaining normal iron levels within the body. Hepcidin also inhibits transport of iron out of macrophages (where iron is stored)

Dr. Monika Nema

The clinical manifestation vary widely in anemia of chronic disease because of its association with so many diseases.

Usually, the signs and symptoms of the underlying disorder overshadow those of the anemia.

Dr. Monika Nema

PALLOR

In the hands, the skin of the palms first becomes pale, but the creases may retain their usual pink color until the Hb concentration is less than 7 g/dl.

Is a sign of anemia.

The pallor associated with anemia is best detected in the mucus membrane of mouth, the conjunctiva, lips and the nail beds

Dr. Monika Nema

LESIONS ASSOCIATED WITH IRON DEFICIENCY ANEMIA Site Findings Nails Flattening, KoilonychiaTongue Soreness, Mild papillary

atrophy, Absence of filiform papillae

Mouth Angular stomatitisHypopharynx Dysphagia,Esophageal

varicesStomach Achlorhydria,Gastritis

Koilonychia

Dr. Monika Nema

LEAD POSIONINGGums in lead poisoning.

Lead lines are shown in gums of this patientsuffering from lead poisoning

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LABORATORY FINDINGS

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DISORDER OF IRON METABOLISM Most microcytic anemia are due to

deficient hemoglobin synthesis often associated with iron deficiency or impaired iron use.

Dr. Monika Nema

IRON DEFICIENCY ANEMIAErythrocytes: If symptoms of anemia are the

presenting complain, the blood hemoglobin is usually 8 g/dl or lower.

MCV – decreased. (Microcytic) MCH- decreased. (Hypochromic) Anisocytosis- Important early sign .

Leading to raised Red Cell Distribution Width.

Few pencil cells, few target cells can be seen.

Dr. Monika Nema

Dr. Monika Nema

IRON DEFICIENCY ANEMIALeukocytes: Usually normal in number. Mild graulocytopenia is seen in long

standing cases. Recent large volume hemorrhage leads

to Neutrophilic Leukocytosis. Due to parasitic infestation, Eosinophilia

can be seen.Thrombocytes: Thrombocytosis is usually seen.

Dr. Monika Nema

PERIPHERAL SMEAR IN IRON DEFICIENCY ANEMIA

Dr. Monika Nema

The normal film shows little variation in red cell

size

The iron deficient cells shows variations in size (anisocytosis) and shape (poikilocytosis), as

well as microcytosis (low average cell size) and

hypochromia (increased central pallor).

Dr. Monika Nema

ANEMIA OF CHRONIC DISEASE Usually normocytic normochromic

anemia is seen. Hypochromia is more common than

microcytosis. Microcytosis in anemia of chronic

disease is usually not as striking as that commonly associated with iron deficiency anemia.

Dr. Monika Nema

In iron deficiency anemia, hypochromia follows microcytosis.

Whereas in anemia of chronic disease, hypochromia preceeds microcytosis.

Dr. Monika Nema

Normocytic picture

Microcytic picture

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CERTAIN NORMAL SERUM LEVELS OF IRON METABOLISM

Dr. Monika Nema

SERUM IRON It is a measure of amount of iron bound

to transferrin. Shows diurnal variation Highest in morning and lowest in

evening. Influenced by recent ingestion and

absorption of iron medication. Normal value : 0.6-1.7 microgram/L.

Dr. Monika Nema

TRANSFERRIN The principal source of iron for

hemoglobin production is that carried by transferrin, the iron transport protein in plasma.

When transferrin saturation with iron is less than 16%, RBC production rate decreases and hypochromic,microcytic cells are manufactured. This state is known as iron deficient erythropoiesis.

Normal transferrin saturation is 16-50%.

Dr. Monika Nema

TOTAL IRON BINDING CAPACITY It is indirect measurement of transferrin

in terms of amount of iron it will bind. Shows slight fluctuation. Normal value : 2.5-4.0 microgram/L.

Dr. Monika Nema

TRANSFERRIN RECEPTOR Disulphide linked transmembrane

protein that facilitates entry of transferrin bound iron into cells.

Dr. Monika Nema

SERUM FERRITIN Ferritin is chiefly intracellular iron

storage protein. Serum ferritin is glycosylated and

contains little or no iron. In most circumstances, Serum ferritin is

proportional to total body iron stores. Not influenced by recent iron therapy. Normal : Male – 15-300 microgram/L. Female – 15-200 microgram/L.

Dr. Monika Nema

SERUM FERRITIN Ferritin levels are the single best serum

measure of storage iron. Serum ferritin level in patient with

anemia of chronic diseases may increase dispropotinately relative to increase in iron stores, probably because ferritin is an Acute phase reactant.

This phenomenon complicates diagnosis of Iron deficiency anemia when it co-exists with inflammatory disease.

Dr. Monika Nema

SERUM LEVEL THAT DIFFERENTIATE ANEMIA OF CHRONIC DISEASE FROM IRON DEFICIENCY ANEMIA

Dr. Monika Nema

Total iron binding capacity – Increased in iron deficiency anemia Decreased in anemia of chronic disease. Erythrocyte sedimentation rate is found

to be elevated in anemia of chronic disease owing to its inflammatory etiology.

Dr. Monika Nema

BONE MARROW FEATURES OF IRON DEFICIENCY ANEMIA

Cellularity – increased Erythroid hyperplasia Micronormoblastic reaction

Normoblast are smaller Late micronormoblast demonstrates persistent

basophilia and fraying of cytoplasmic borders indicating lack of complete hemoglobinization

Myelopoiesis – Normal Megakaryopoiesis – Normal Depleted bone marrow iron

Dr. Monika Nema

Dr. Monika Nema

BONE MARROW FEATURES OF ANEMIA OF CHRONIC DISEASE

Bone marrow aspirate demonstratingincreased iron staining in a fragment representing increased marrow iron stores. . This finding is present in a patient with anemia of chronicdisease.

Normal iron staining in histiocytes is shown for comparison

Dr. Monika Nema

CRITERIA FOR GRADING IRON STORESGrade Criteria

0 No iron granules observed

1+ Small granules in reticulum cells, seen only in oil immersion lens

2+ Few small granules seen with low power lens

3+ Numerous small granules in all marrow particles

4+ Large granules in small clumps

5+ Dense, large clumps of granules

6+ Very large granules, obscuring marrow details

Normal Marrow =1+ To 3+

Dr. Monika Nema

THALASSEMIA MINOR Red cell count is increased. MCV –decreased. MCH- decreased. MCHC- normal or slightly decreased. Reticulocytes are generally increased to

twice the normal number and have been found to correlate with hemoglobin level.

Dr. Monika Nema

Dr. Monika Nema

PERIPHERAL PICTURE OF THALASSEMIA MINOR

Target cells

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PERIPHERAL PICTURE OF THALASSEMIA MINOR

Basophilic stippling in thalassemia.

Dr. Monika Nema

THALASSEMIA MINOR V/S IRON DEFICENCY ANEMIA

Dr. Monika Nema

THALASSEMIA MINOR V/S IRON DEFICENCY ANEMIA

Findings Thalassemia minor

Iron deficiency anemia

Anisocytosis Mild or absent Early and prominent finding

Microcytosis More severe Less severe

Dr. Monika Nema

Dr. Monika Nema

MENTZER INDEX

Mentzer index=Mean cell volume

Red cell count

Value greater than 14 is found in iron deficiency anemia whereas value less than 12 is seen in thalassemia trait disorder.

Value between 12-14 is considered indeterminate.

Dr. Monika Nema

KERMAN INDEX 1 Calculated as MCV x MCH

Red cell count

>371: normal

321-370: iron def.=> trial of iron for 1 mo.

251-320: Mixed iron def. & minor thalassemia => trial of iron & folate then check CBC & Hb elect

<250 : Minor thalassemia =>check Hb elect.

Sensitivity =99% , Specificity=86%

Dr. Monika Nema

KERMAN INDEX 2 Calculated as MCV x MCH

Red cell count x MCHC

>13: Normal

10.5-13: Iron deficiency

8-10.5: Mixed iron def & minor thalassemia.

<8 : Minor thalassemia

Note : Sensitivity=99% , Specificity=93%

Dr. Monika Nema

SPECIAL TEST HbF

Electrophoresis

High performance liquid

chromatography

DNA analysis

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Hb A 2 ranges 3.5 to 7.0 % Hb F ranges 1 – 3 %

Dr. Monika Nema

BONE MARROW FEATURES OF THALASSEMIA Hypercellular Erythroid hyperplasia M:E ratio 1:5 Dyserythropoisis Myelopoisis and megakaryopoisis are

normal Bone marrow iron increased

Dr. Monika Nema

BONE MARROW FEATURES OF THALASSEMIA

Top and bottom panels show bone marrow aspirate andbiopsy, respectively, from a case of thalassemia trait.

The bone marrow has increased numbers of erythroid precursors (a low myeloid to erythroid ratio) related to the increased peripheral RBC destruction in this disease.

Dr. Monika Nema

SIDEROBLASTIC ANEMIA Peripheral smear: microcytic

hypochromic ,anisopoiklocytosis ,few cell show basophilic stippling,WBC and platelet normal.

Serum iron and percent transferrin saturation increased

Bone marrow: hypercellular,normoblastic or micronormoblastic reaction with vacuolation in cytoplasm, sideroblast , megakaryopoisis and normal myelopoisis.

Dr. Monika Nema

Sideroblastic anemia. Normocytic cells are present, along with a minor population of microcytic, hypochromicerythrocytes possessing a thin rim of cytoplasm. Occasional teardrop cells are visible.

Dr. Monika Nema

RING SIDEROBLAST

Dr. Monika Nema

In Sideroblastic anemia. Numerous ringed sideroblasts are seen in this marrow aspiratesmear stained for iron. They are normoblasts with ≥10 iron-containing granules in the cytoplasmencircling at least one-third of the nucleus.

Dr. Monika Nema

LEAD POSIONINGPeripheral blood film demonstrating coarsebasophilic stippling. Normocytic or microcytic anemia may be present.

Dr. Monika Nema

Dr. Monika Nema

Dr. Monika Nema

THANK YOU PRESENTED BY :- DR.MONIKA

NEMA