ANAEMIA

BY:- Saifuddin Lala

M.B.A(Pharma)

DEFINATION[1]

Anaemia is define as reduction of the erythrocyte

mass in the blood. In anaemia either the no. of

erythrocyte are reduced or erythrocyte are deficient in

the oxygen binding pigment haemoglobin.

INTRODUCTION[1] [2]

At the sea level, the average normal men has a 5.4

* 106 erythrocytes/mm3 & these erythrocytes

contain 16 g of haemoglobin/dl of blood.

The volume occupied by the erythrocyte is 47% of

the blood & is called as haematocreat. The

haemoglobin level, below which the anaemia is

likely to manifest are given below.

NORMAL HAEMOGLOBIN VALUE

AGE AND SEX HAEMOGLOBIN LEVELE g/dl

1) 6 MONTHS-6YEARS 11

2) 6 YEARS-14 YEARS 12

3) MEN 13

4) WOMEN 12

5) PREGNANT WOMAN 11

HAEMOGLOBIN

GENERAL SYMPTOMS OF ANAEMIA

CONT...

There are approx 100 different types of anaemia few of

them are classified as follow.

MYCROCYTIC ANAEMIS

Iron deficiency anaemia.

Anaemia of chronic disease.

Sideroblastic anaemia.

MEGALOBLASTIC ANAEMIAS

Float deficiency anaemia.

Vit.B-12 deficiency anaemia.

CONT...

HAEMOLYTIC ANAEMIAS

Auto immune haemolytic anaemia.

Sickle cell anaemia.

Thalassaemia.

Anaemia due to glucose-6-phosphat

dehydroginase deficiency.

Paroxysmal nocturnal haemoglobinuria.

IRON DEFICIENCY ANAEMIA[3][4]

Iron is critical for the growth of all cells. It is therefore not

surprising that iron-deficiency anemia independently

increases morbidity and mortality.

1] IRON PROFILE IN BODY:-

Most adults have 45 mg/kg elemental iron in their

bodies. Females generally have lower levels than

males.

Within that pool of total body iron, approximately two

thirds is contained in heme and one third in the storage

forms of ferritin or hemosiderin.

CONT…

To maintain adequate supplies of iron for heme

synthesis, 20 mg of iron is recycled daily, from

senescent red cells that are removed from the

circulation to new cells in the bone marrow.

Approximately 1 to 2 mg per day of additional dietary

iron is needed to balance losses in urine, sweat, and

stool.

MANAGEMENT[5]

MANAGEMENT[5]

Human erythropoietin can also be administrated.

Transfusion should be prescribed ONLY for conditions

for which there is NO OTHER TREATMENT.

Transfusion should not be prescribed when patient have

congestive cardiac failure, chronic kidney disease, or

liver dysfunction.

So in such kind of patients, we can administrated

packed RBC.

ANAEMIA OF CHRONIC DISEASE[1]

A mild anaemia is often associated with chronic

diseases. E.g. chronic infection, renal failure &

rheumatoid arthritis etc.

The cause of anaemia is not well understood but

adaptive physiological response to the inflammation

may be responsible.

MEGALOBLASTIC ANAEMIA

Megaloblastic anemia is a blood disorder in which there

is anaemia with larger than normal red blood cells[7].

SIGN AND SYMPTOM[6]

The anemia symptoms of both folic acid deficiency and

vitamin B12 deficiency are the same. In both there are

often gastrointestinal tract symptoms e.g. anorexia and

diarrhea occur because the epithelial cells lining the

intestines also have a rapid turnover.

SIGN AND SYMPTOM[6]

Frequently the patient does not seek medical help

until some of the following conditions occur:

weakness, palpitations, angina, and symptoms of

congenital heart failure. Folic acid deficiency results

in anemia and intestinal manifestations but not

neurological symptoms.

CAUSES OF VITAMIN B AND FOLET

DEFICIENCIES[8]

PATHOPHYSIOLOGY

LABORATORY INVESTIGATION

FURTHER INVESTIGATION

Additional tests to establish the cause of low b12

concentration

Parietal cell and intrinsic factor antibodies: a positive

result for intrinsic factor antibodies is diagnostic of

pernicious anaemia as this is a more specific assay.

The Schilling test for B12 absorption is no longer

available. Upper gastrointestinal endoscopy, when

upper gastrointestinal symptoms or co-existing iron

deficiency are present, chiefly to exclude gastric

carcinoma, which occurs in 5% of patients with

pernicious anaemia.

FURTHER INVESTIGATION

Additional tests to establish the cause of folate

deficiency

In the absence of dietary deficiency (common in the

elderly), a malabsorption syndrome (e.g. coeliac

disease) should be excluded, particularly in patients with

mixed iron and folate deficiency.

Coeliac screening estimation by detection of endomysial

antibodies (EMA-IgA), anti-tissue transglutaminase (tTG

IgA/IgG) and anti-gliadin (AGA IgA, AGA IgG)

antibodies.

If the diagnosis is still in doubt, jejunal biopsy is the gold

standard test.

FURTHER INVESTIGATION

Bone marrow examination

It is rarely necessary in B12/folate deficiency, but should

be done if assay values are inconclusive, particularly if

the patient is pancytopenic, to exclude aplasia,

myelodysplasia or neoplasia.

However, it is mandatory in other macrocytic conditions,

especially to demonstrate the characteristic

dyshaemtopoiesis of a myelodysplastic disorder.

MANAGEMENT:-

B12 DEFICIENCY

Loading doses of hydroxocobalamin 1mg are

administered I.M 3 times per week to a total of 6 doses

in the first 2 weeks. Thereafter, it is given 3-monthly for

life in cases of B12 malabsorption.

However, in dietary deficiency, maintenance oral

supplementation with cyanocobalamin may be given

once tissues stores have been replenished.

Blood transfusion should be avoided even in severe

anaemia, unless symptoms or cardiovascular risks

dictate otherwise.

MANAGEMENT:-

Neurological complications may develop even in the absence

of anaemia, therefore it is essential to initiate treatment as

soon as the diagnosis is made. Folic acid must not be

initiated before B12 as this can precipitate or aggravate

neurological complications.

FOLATE DEFICIENCY

Folic acid is given at a dose of 5 mg daily orally for about 4

months to replenish tissue stores. Dietetic advice should be

given if dietary deficiency is the cause. Prophylactic folate

supplements, 400 μg daily, are recommended for pregnant

women to reduce fetal neural tube defects.

HAEMOLYTIC ANAEMIA

Haemolytic anaemia results from the early

destruction of an erythrocyte, from a variety of

causes, either inherited, or acquired. The

mechanism may be via intravascular or

extravascular damage.

1] SICKLE CELL DISEASE

Sickle cell disease (SCD) results from the recessive

inheritance of a mutant β globin gene in which

valine is substituted for glutamic acid at position 6

of the β -globin chain, resulting in the formation of

sickle haemoglobin (HbS).

CONT’D

SCD comprises a group of conditions in which HbS is

present either in the homozygous form, HbSS, or in

association with other variant haemoglobins; HbC, HbE

HbDPunjab, HbOArab, β-thalassaemia plus (β +) or β –

thalassaemia zero (β0) leading to HbSC, HbSE and so

on.

PATHOPHYSIOLOGY:

Normal adult haemoglobin (HbA) is soluble whereas

HbS is hydrophobic and has the singular property of

polymerizing to form rigid bundles when deoxygenated.

CONT’D

These bundles twist the shape of the red cell and damage its

membrane leading to irreversibly sickled cells, which are targets for

phagocytosis.

Sickle cells have lifespan of 16-20 days. Vasoocclusion by cells is

not only case of sickle cells blocked microvasculature, but SCD is a

chronic inflammatory condition with elevated conc. of inflammatory

mediators and free radicals.

There is red cell dehydration and abnormal interaction with vascular

endothelium & NO depletion, all contributing to vasoocclusion, the

hallmark of sickle cell disease.

VASO-OCCLUSION

DIAGNOSIS AND LABORATORY FEATURES

Full blood count (FBC) will make known anaemia with a high

reticulocyte count and blood film may show sickle cells. Serum

bilirubin may be elevated as may serum lactate

dehydrogenase.

The sickle solubility test quickly confirms the presence of

sickle haemoglobin but is unable to differentiate unaffected

carrier status from the disease.

The most widely used diagnostic test is HPLC, which

separates haemoglobins according to their charge. Isoelectric

focusing and mass spectrometry are used as alternatives in

some laboratories.

MANAGEMENT

Exchange blood transfusion (EBT), where venesection

is carried out simultaneously with transfusion to avoid

raising the haematocrit, as this may cause

hyperviscosity.

EBT can be carried out manually or by automated

erythro-cytopheresis but is associated with a poorer

outcome.

Hydroxycarbamide therapy is then commenced in

patients with severe disease, aiming to improve it.

This results in increased HbF% and reduced white

blood cell and platelet counts, and increases the mean

CONT’D

Use of hydroxycarbamide is associated with reduced

mortality and decreased frequency of painful crisis and acute

chest crisis.

Allogeneic stem cell transplant is the only known cure for

sickle cell disease and although over 200 transplants have

been successfully carried out with less than 5% mortality

rates worldwide.

Its use has been limited in adults by toxicity and the

availability of a suitably fully human leukocyte antigen

matched donors.

Recent successful transplants using 50% matched related

donors and less toxic regimens9,10 offer much greater hope.

THALASSAEMIA

Thalassaemia is an inherited disorder of Hb synthesis where

mutations of the globin gene lead to various degrees of

quantitative defect in globin production and an imbalance in β

globin chain synthesis, resulting in ineffective erythropoiesis

and anaemia.

α-THALASSAEMIA

There are four a-globin genes, two inherited from each

parent, loss of up to two genes does not result in a clinically

apparent syndrome (permutations are; aa/a-,a-/a-,aa/–)

however loss of three genes (a-/–) results in haemoglobin H

disease, associated with anaemia and a degree of

haemolysis.

CONT’D

These patients occasionally require transfusional

support. Loss of all four genes results in death due to

profound anaemia.

β -THALASSAEMIA:

β-thalassaemia is a recessively inherited disorder where

there is a reduction (b+) or absence (b0) of normal b-

globin chains.

It is divided into three broad clinical phenotypes.

Individuals with β-thalassaemia major are completely

dependent on blood transfusion support from the first

year of life, usually due to homozygous inheritance of

b0.

CONT’D

Thalassaemia minor (trait) patients inherit a normal b gene in

association with either b+ or b0, and are asymptomatic but may

have a mild anaemia with invariably low MCV and mean cell

haemoglobin (MCH).

The third group is a heterogeneous group of patients with

diverse phenotypes intermediate to thalassaemia major and

minor, referred as thalassaemia intermedia.

Pathophysiology

The anaemia in β-thalassaemia results from ineffective

erythropoiesis, peripheral haemolysis and the overall reduction

in haemoglobin synthesis.

PATHOPHYSIOLOGY

The reduced or absent β-globin production leads to precipitation of

excess α-globin chains in red cell precursors within the

haemopoietic tissue and results in their early destruction.

The effect of this ineffective erythropoiesis, a compensatory

erythroid hyperplasia, expansion of haemopoietic tissue within

expanded marrow spaces, extramedullary haemopoiesis &

hepatosplenomegaly in the absence of adequate transfusion.

These patients also have markedly increased iron absorption,

made worse with transfusional iron overload, and the condition

leads to early mortality if untreated.

CLINICAL INVESTIGATION & MANAGEMENT

CBC confirms a microcytic & hypochromic anaemia, and

blood film shows red cells that are nucleated and have

basophilic stippling.

HPLC will reveal an absence of HbA in thalassaemia major,

raised haemoglobin A2 in thalassaemia intermedia patients

with variable amounts of HbA and HbF, & raised haemoglobin

A2 in thalassaemia trait.

children with untreated or partially treated thalassaemia

major die in the first or second decade of life. Clinical

management is based on adequate, safe blood transfusions

& prevention of iron overload.

REFERENCES

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4] Kemna EH, Tjalsma H, Willems HL, Swinkels DW. Hepcidin: from discovery

to differential diagnosis. Haematologica. 2008;93:90-97.

5] Michael Alleyne , McDonald K. Horne , Jeffery L. Miller: Individualized

Treatment for Iron-deficiency Anemia in Adults The American Journal of

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