ANAEMIA DEFINITION

Anaemia is defined as the deficiency of Hb

concentration in the blood resulting in its
decreased oxygen carrying capacity.

WHO defines anaemia as Hb level :

In males- <13g/dl
In females- <12g/dl
 NORMAL VALUES OF HB
• Newborns: 17 to 22 gm/dl
• Babies 1 week of age: 15 to 20 gm/dl
• Babies 1 month of age: 11 to 15 gm/dl
• Children: 11 to 13 gm/dl
• Adult men: 14 to 18 gm/dl
• Adult women: 12 to 16 gm/dl
• Men after middle age: 12.4 to 14.9 gm/dl
• Women after middle age: 11.7 to 13.8 gm/dl
 Epidemiology
• Most common condition in the world.

• Worldwide, over 50% pregnant women and over 40%

of infants are anaemic.

• In Britain, 14% of women aged 55-64 and 3% of men

aged 35-64 yrs are found to be anaemic.

• Common in cancer patients receiving chemotherapy

and patients with chronic kidney disease (CKD).
 ETIOLOGY
• Blood loss

• Decreased production of RBC’s

• Increased destruction of RBC’s

 Classification
MACROCYTIC ANAEMIAS
1. MEGALOBLASTIC ANEMIAS
a) VITAMIN B12 DEFICIENCY ANAEMIAS
b) FOLIC ACID DEFICIENCY ANAEMIAS
MICROCYTIC ANAEMIAS
1. IRON DEFICIENCY ANAEMIAS
2. SICKLE CELL ANAEMIAS
3. SIDEROBLASTIC ANAEMIAS
4. THALASSEMIA
5. GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY ANAEMIA.
NORMOCYTIC ANAEMIAS

1. RECENT BLOOD LOSS

2. HEMOLYSIS
3. BONE MARROW FAILURE
4. RENAL FAILURE
5. ANEMIA OF CHRONIC DISEASE
6. ENDOCRINE DISORDERS
7. MYELOPLASTIC ANAEMIAS
 IRON DEFICIENCY ANAEMIA
Iron deficiency anaemia is the defect in haemoglobin
synthesis. Red blood cells are small and contain decreased
amount of haemoglobin.

EPIDEMIOLOGY
• most common nutritional deficiency and present up to 20%
of world population.

• Diet deficient in iron, parasite infestation and multiple

pregnancies contributes to its high prevalence in
underdeveloped countries
 Aetiology
• Blood loss.
• Inadequate iron absorption.
• In women of child bearing age this occurs frequently.
• In 50% of adults, this occurs due to gastrointestinal
bleeding.
• Increased physiological demand.
 PATHOPHYSIOLOGY
• Body iron requirement exceeds iron intake, causing
progressive depletion of bone marrow iron stores.
• Deficiency is severe enough to impair red blood cell
biosynthesis, leading to anaemia.
 Clinical manifestations
• Extreme fatigue • Painful glossitis
• Koilonychias • Fast heartbeat
• Pale skin • Pica
• Weakness • Poor appetite
• Shortness of breath • Restless leg’s
• Chest pain syndrome
• Frequent infections • Dysphagia
• Atrophic gastritis. • Angular stomatitis
 DIAGNOSIS
`
• Complete blood count
• Poikilocytosis.
• Low serum ferritin level (<15μg/L)
• MCV 60-90fL
• TIBC >400μg/ dL
• Serum iron <30μg/dL
TREATMENT
 PHARMACOLOGICAL THERAPY
ORAL IRON THERAPY
•Ferrous sulphate 200mg 3 times a day for upto 6
months.
•Ferrous gluconate 300-1200mg
•Ferrous fumarate 200-600mg
PARENTERAL IRON THERAPY
•Iron dextran, 50 mg of iron/ mL, given by IV or IM route
•Sodium ferric gluconate is supplied in 5mg ampoules
containing 62.5 mg of elemental iron.
•Iron sucrose is available in 5-mL single-dose vials. Each
vial contains 100 mg of iron sucrose.
• Iron sorbitol as IM injection with maximum individual
dose of 100mg.
 NON-PHARMACOLOGICAL THERAPY

• IRON RICH DIET

 meats like beef, pork, lamb, liver
 poultry
 fish- shellfish, oysters
 green leafy vegetables
 legumes- dry beans
 TRANSFUSIONS
•Based on the evaluation of risks and benefits.

•Requires extreme caution with existing cardiovascular

compromise.
SIDE EFFECTS
•Nausea, constipation, stomach upset, and vomiting
•Stool darkening.
•Itching, heart palpitations, and dizziness
•Iron dextran, can cause serious life-threatening allergic
reactions in some people.
 Megaloblastic anaemia
•Megaloblastic anaemia is characterised by impairment of
DNA synthesis, leading to abnormally large erythroid
precursors and red cells.

•Abnormality in the maturation of hematopoietic cells in

the bone marrow.

•Two major causes are folate and vitamin B12 deficiency.

1. Folate deficiency

Epidemiology
• Most common in US.

Aetiology
• Dietary deficiency
• Increased folate utilization
• Pregnancy
• Inflammatory conditions
• Some medicines like methotrexate, triamterene,
phenytoin, barbiturates.
 Pathophysiology
• Inhibition of DNA synthesis in maturing cells.

• Defective DNA synthesis mainly affects cells such

as gastrointestinal cells and precursors of red blood
cells in bone marrow

• Folate co-enzyme is oxidized to dihydrofolate form,

which is inactive.

• This anaemia is typically caused by a poor diet, in

which adequate amounts of folic acid are lacking

• Folate deficiency often occurs during pregnancy.

 Folate metabolism
Dietary folate
gut
Folate monoglutamate

Methyl tetrahydrofolate monoglutamate

Tetrahydrofolate monoglutamate
bone
Tetrahydrofolate polyglutamate marrow

Folate co-enzymes dihydrofolate enzymes

 Clinical manifestations
•Pallor •Diarrhoea
•Progressive fatigue •Glossitis
•Anorexia •Palpitations
•Irritability •Mild jaundice

Diagnosis
•Full blood count carried out.
•Serum folate level <3 ng/ml
•RBC folate level <150 ng/ml
•Elevated homocysteine level.
•Anisocytosis and poikilocytosis are common
•Some neutrophils – hyper segmented
•Thrombocytopenia
 Treatment
•Replacement therapy
•5-15mg of folic acid daily dose for 4 months
• Vitamin and mineral supplements
•Eating foods high in folic acid such as wheat germ, beef
liver, red beans, oat meal.
Side effects
•Hives
•Nausea, loss of appetite
•Bitter or unpleasant taste in your mouth
•Sleep problems
•Depression
•Feeling excited or irritable
2. Vitamin B-12 deficiency anemia
Epidemiology
•Strict vegetarians and in elderly people.
•Patients with gastrectomy and 6% of those having partial
gastrectomy.
•Most common in people of northern European descent.

Aetiology
•Inadequate intake of food like meat, milk and eggs
•Malabsorption
•Intestinal pathologies
•Immunologically related diseases
•Partial gastrectomy.
Pathophysiology
 Clinical manifestations
• Progressive neuropathy
• Altered bowel habit
• muscle weakness
• Weakened bones and hip fracture
• Mild jaundice
• glossitis
• Dyspnoea
 Diagnosis
• Complete blood count.
• Low serum vitamin B-12 level < 100 pg/ml
• Low haematocrit 10% - 15%
• No. Of RBC’s, platelets decreased
• Mean corpuscular volume greater than 100fL
• Reticulocyte count decreased
• Homocysteine and methylmalonic acid levels increased.
• Intrinsic factor antibodies and parietal cells antibody.
• Bone marrow aspiration
• Anisocytosis and poikilocytosis
 Treatment
• Lifelong Replacement therapy
• Hydroxycobalamin as IM injection 1mg for 3 times a week
for 2 weeks.
• vit B 12 Oral doses may be initiated at 1 to 2 mg daily for 1
to 2 weeks, followed by 1-mg daily.
• Potassium supplements.

Side effects
GI disturbances, hypersensitivity reactions, Bronchospasm.
 Sickle cell anaemia
Sickle cell anaemia (SS) is a congenital
haemolytic anaemia resulting from defective
haemoglobin molecules . It occurs by a mutation
in the β-globin chain gene that creates sickle
haemoglobin (Hb S).
Epidemiology
• Primarily in persons of African and
Mediterranean descent.
• In UK, approx. 5000 people , largely from Afro-
caribbean population, have sickle cell anaemia.
 Aetiology
• Hemoglobin S

• Valine substituted for glutamic acid as the sixth

amino acid in the β-polypeptide.

• SCT is carrier of gene and is asymptomatic.

Pathophysiology
• The membrane of red cells containing HbS is
damaged, which leads to intracellular
dehydration.

• When the patient’s blood is deoxygenated,

polymerisation of Hb S occurs, forming a
semisolid gel.

• Anaemia results from increased destruction of

red cells.
 Clinical manifestations
• Severe pain.
• Anorexia
• Chronic anaemia.
• Chest pain and difficulty in breathing.
• Strokes.
• Arthralgia.
• Severe infections.
• Jaundice, dark urine.
• Splenomegaly, hepatomegaly.
 Diagnosis
• Haemoglobin electrophoresis, showing HbS.
• Hb level 7-10g/dl
• Elevated WBC and platelet counts.
• A positive sickling test with a reducing substance
sodium metabisulfite.
 Treatment
• Hydroxyurea 10-30 mg/kg per day increases total and
foetal hemoglobin.
• Penicillin V 250 mg twice a day.
• Cytarabine, Vinblastine, erythropoietin, hydroxycarbamide.
• Morphine or meperidine is used as an analgesic.
• Oxygen administration for hypoxia.
 Anaemia of chronic disease
ACD is a common type of anaemia that occurs in
patients with infectious, inflammatory, or neoplastic
diseases that persist for more than 1 or 2 months.

Epidemiology
• About 57% of hospitalised patients have ACD.
• Second most common form.
• In US, one third of the cases of prevalence of anaemia in
adults aged 65 years are due to chronic disorders.
 Aetiology
• Decreased erythropoietin production.
• Inflammatory cytokines.
• Cytotoxic treatments.
• Chronic kidney and heart disease.
 Pathophysiology
•Hepcidin, produced by the liver is encouraged by pro
inflammatory cytokines, especially IL-6.
•Hepcidin binds to ferroportin on the membrane of iron
exporting cells, internalising the ferroportin.
•Inhibit the export of iron from these cells into the blood.
• The iron remains trapped inside the cells in the form of
ferritin.
 Clinical manifestation
• Fatigue, weakness • Chest pain,
• Headache palpitations
• Dizziness • Difficulty in sleeping
• Vertigo or concentrating
• Tinnitus • Anorexia
• Syncope • Dyspnoea
 Diagnosis
• Serum iron level is low

• Ferritin is normal or high, reflecting the fact

that iron is sequestered within cells.

• TIBC is low or normal

 Treatment
• Epoetin alfa 50 to 100 units/kg three times weekly. If
haemoglobin does not increase after 6 to 8 weeks 150
units/kg three times weekly or, in patients with AIDS, to 300
units/kg three times weekly.

• Iron supplements should only be used for patients with

established iron deficiency.

• Transfusion of packed red blood cells should be reserved

for patients who have severe symptomatic anaemia.
.
Novel erythropoiesis-stimulating protein (NESP) -
darbepoetin alfa - stimulates erythropoiesis by the same
mechanism as recombinant human erythropoietin
(rHuEPO).
ADVERSE REACTIONS
•Hypertension
• headache
•Tachycardia
•nausea, vomiting, diarrhoea
•skin rashes, fever
•myalgia
•skin reaction at the injection site.
 Haemolytic anaemia
Haemolytic anaemias are resulting from an increase in the
rate of red cell destruction.
The premature destruction of red cells in haemolytic
anaemia may occur by 2 mechanisms:

• Firstly, the red cells undergo lysis in the circulation and

release their contents into plasma (intravascular haemolysis).

• Secondly, the red cells are taken up by cells of the RE

system where they are destroyed and digested ( extra vascular
haemolysis).
 Epidemiology
• Haemolytic anaemia represents approximately
5% of all anemias.

• AIHA is slightly more likely to occur in females

than in males. G-6-PD deficiency is an X-linked
recessive disorder. Therefore, males are usually
affected, and females are carriers.

• AIHA is more likely to occur in middle-aged and

older individuals.
 Aetiology
• Inability of bone marrow to replace the red blood cells
that are being destroyed.
• When the immune system mistakenly sees own red blood
cells as foreign substances
• Exposure to certain chemicals, toxins, and drugs like
cyclosporin, levodopa, penicillin, quinidine.
• Infections
• Blood clots in small blood vessels
• Transfusion of blood from a donor that does not match.
Classification
 Pathophysiology
•Presence of auto-antibodies.

•Acquired disorders result mainly from a direct effect on the

membrane and alterations in Hgb or metabolism.

•Alterations in Hgb solubility or stability, cause cell

deformations leading to haemolysis.

•Alterations in cell metabolism by changing cell dimensions

and Hgb solubility.
 Clinical features
• paleness of the skin. • dizziness.
• fatigue. • weakness/inability to
• fever. do physical activity.
• confusion Diagnosis• Light headedness
Complete Blood Count
Reticulocyte count. high reticulocyte counts because bone
marrow is working hard to replace the destroyed red blood
cells.
Peripheral smear. Some types of haemolytic anaemia
change the normal shape of red blood cells.
Coombs' test. This test can show whether body is making
antibodies (proteins) to destroy red blood cells
 Treatment
Definitive therapy depends on the cause:
• Symptomatic treatment by blood transfusion.
• In severe immune-related haemolytic anaemia,
steroid therapy is used.
• Azathioprine or cyclosporine can be given.
• Rituximab
• Sometimes Splenectomy can be helpful
 Aplastic anaemia
Aplastic anaemia is a blood disorder in which the body's bone
marrow doesn't make enough new white blood cells, red
blood cells and platelets.
 Epidemiology
• The annual incidence of aplastic anaemia is
about two cases per million population.

• Aplastic anaemia is 2-3 times more common in

Asia than in the West.

• Acquired aplastic anaemia is most commonly

present between the ages of 15 years and 25
years.
 Causes
Acquired Causes
• Toxins, such as pesticides, arsenic, and benzene.
• Radiation and chemotherapy (treatments for cancer).
• Medicines, such as chloramphenicol.
• Infectious diseases, such as hepatitis, Epstein-Barr virus,
cytomegalovirus, parvovirus B19, and HIV.
• Autoimmune disorders, such as lupus and rheumatoid arthritis.
• Pregnancy
• Sometimes, cancer from another part of the body can spread to
the bone and cause aplastic anemia.

Inherited Causes
• Certain inherited conditions can damage the stem cells and lead
to aplastic anemia.
 Signs and symptoms
• Shortness of breath bruising
• Rapid or irregular heart • Nosebleeds and bleeding
rate gums
• Pale skin • Prolonged bleeding from
• Frequent or prolonged cuts
infections • Skin rash
• Unexplained or easy
 PATHOPHYSIOLOGY
Antigens are presented to T cells, which trigger T cells to
activate and proliferate. Increased production of interleukin-2 leads
to the polyclonal expansion of T cells. An immunological cascade
results in the production of a number of mediators and toxic effects,
leading to reduced cell cycling and cell death by apoptosis, and
ultimately resulting in bone marrow failure.
• Haemoglobin
Diagnosis
levels are moderately reduced. Normocytic,
normochromic anaemia but sometimes macrocytosis may be
present. The reticulocyte count is reduced or zero.

• Leucopenia. The absolute granulocyte count is particularly

low (below 1500/μl) with relative lymphocytosis.

• Thrombocytopenia

• Bone marrow aspiration. Patchy cellular areas in an aplastic

marrow due to replacement by fat.
Treatment
Treatment options include:

• Allogenic stem cell transplantation (SCT)

• Immunosuppressive therapy
• Supportive care (e.g. blood transfusions,
management of infections)
• Iron chelation therapy
 Drugs used
• Campath- alemtuzumab
• Neoral- cyclosporin
• Cytoxan- cyclophosphamide
• Zenapax- daclizumab
 Sideroblastic anaemias
• Sideroblastic anaemias are a heterogeneous
group of disorders with ring sideroblasts in the
bone marrow and impaired haeme biosynthesis.

• There are both hereditary and acquired forms.

Epidemiology
• Hereditary forms are rare.
• Acquired forms are common including 30% of
alcoholics admitted in hospitals
 Aetiology
Hereditary form

• x chromosome linked pattern inheritance.

• 5-ALAS mutation

Acquired form

• Myelodisplastic syndrome
• Nutritional deficiencies (copper, vitamin B-6)
• Lead poisoning
• Zinc overdose
• Alcohol
• Drugs like isoniazid, chloramphenicol, cycloserine ,
pyrazinamide, pencillamine.
• Idiopathic
 Pathophysiology

Heme biosynethsis begins in the mitochondrion with the

formation of 5-aminolevulinic acid. This molecule moves to
the cytosol where a number of additional enzymatic
transformations produce coproporphyrinogin III. The latter
enters the mitochondrion where a final enzymatic conversion
produces protophorphyrin IX. Ferrochelase inserts iron into
the protophorin IX ring to produce heme.
Defects in the steps of heme biosynthesis that occur
within the mitochondrion produce sideroblastic
anemias. For instance, perturbations of the enzymatic
activity of delta-amino Levulinic acid synthase (ALAS)
produce sideroblastic anaemia
 Clinical manifestation
• Fatigue, decreased tolerance to physical activity, and dizziness
• Splenomegaly
• Thrombocytopenia

Diagnosis
• Specific test: Prussian blue stain of RBC in marrow shows
ringed sideroblasts.
• Basophilic stippling is marked and target cells are common
• The MCV is commonly decreased.
• Serum iron, percentage saturation and ferritin are increased.
The TIBC is normal to decreased.
• Hematocrit of about 20-30%
 Treatment
• initial dose of pyridoxine should be 100-200mg daily orally
with a gradual escalation to a daily dose of 500mg.

• blood transfusions to maintain an acceptable haemoglobin

level

• Iron chelation with desferrioxamine is the standard treatment

for transfusional hemeochromatosis.

• Thiamine, or folic acid; transfusion (along with antidotes if

iron overload develops from transfusion).

• bone marrow or liver transplantation.

 Thalassaemia
The thalassaemias are a diverse group of hereditary
disorders in which there is reduced synthesis of one
or more of the globin polypeptide chains.

Epidemiology
• Thalassaemias were first described in people of
Mediterranean countries.
• The condition also occurs in the Middle East, Indian
subcontinent, South-East Asia and in blacks.
 Classification
Thalassaemias are classified into
• α- and β- thalassaemias.
Each of the two main types of thalassaemias may occur
as
• heterozygous (called α- and β-thalassaemia minor or
trait), or as
• homozygous state (termed α- and β-thalassaemia
major).
 Aetiology
• α-Thalassaemia: In α-thalassaemia major, it is the inability
to synthesise adult haemoglobin, while in α-thalassaemia
trait there is reduced production of normal adult
haemoglobin.

• β-Thalassaemia: In β-thalassaemia major, it is the

premature red cell destruction. In β-thalassaemia minor,
very mild ineffective erythropoiesis, haemolysis and
shortening of red cell lifespan occurs.
 Pathophysiology
• α-thalassaemias: defective synthesis of α-globin
chains resulting in depressed production of
haemoglobins that contain α-chains i.e. HbA, HbA2
and HbF. α- thalassaemias are due to deletion of one
or more of the α-chain genes located on short arm of
chromosome16.

• Beta thalassemia: deficient or absent synthesis of

beta globin chains, leading to excess alpha chains.
Beta globin synthesis is controlled by one gene on
each chromosome 11.
 Clinical manifestation
• Bone deformity
• Growth retardation
• Splenomegaly

Diagnosis
•complete blood count shows a mild microcytic anemia
•The MCV is usually less than 75 fL with thalassemia
•Microcytic anemia with a normal RDW will almost always be
because of thalassemia.
 Treatment
• Regular blood transfusions (4-6 weekly) to maintain
haemoglobin above 8 g/dl
• Desferrioxamine S/C or IV, has been the treatment of
choice.
• Bone marrow transplantation in childhood is the only
curative therapy for beta thalassemia major
• Splenectomy is beneficial in children over 6 years of
age