Anaemia can be defined as a reduction from normal of the quantity of haemoglobin in the blood. It is not one disease, but a condition that results from a number of different pathologies. The World Health Organisation defines anaemia in adults as haemoglobin levels less than 13g/dL for males and less than 12g/dL for females. The low haemoglobin level results in a corresponding decrease in the oxygen-carrying capacity of the blood. Anaemia is possibly one of the most common conditions in the world and results in significant morbidity and mortality, particularly in the developing world.

1. PRESENTED BY-
MD ALTAMASH AHMAD
PHARM D 4TH YEAR
ROLL - 1850951001
ANANDITA GULATI
PHARM D 4TH YEAR
ROLL - 1850951002

2. INTRODUCTION
• Anaemia can be defined as a reduction from normal of the quantity of haemoglobin
in the blood.
• It is not one disease, but a condition that results from a number of different
pathologies.
• The World Health Organisation defines anaemia in adults as haemoglobin levels less
than 13g/dL for males and less than 12g/dL for females.
• The low haemoglobin level results in a corresponding decrease in the oxygen-
carrying capacity of the blood.
• Anaemia is possibly one of the most common conditions in the world and results in
significant morbidity and mortality, particularly in the developing world.

3. ETIOLOGY (CAUSES)
The low haemoglobin level that defines anaemia results from two different
mechanisms:
1. Increased haemoglobin loss due to either:
– haemorrhage (red cell loss) or
– haemolysis (red cell destruction).
E.g. – Menstrual bleeding, excessive accidental bleeding, internal bleeding, etc.
2. Reduced haemoglobin synthesis due to either:
– lack of nutrient or
– bone marrow failure
E.g. - Iron deficiency, folate deficiency, vitamin B12 deficiency, etc.

4. TYPES:
1. Microcytic anemias-
• Iron deficiency anemia
• Anemia of chronic disease
• Sideroblastic anemia
2. Megaloblastic anemias-
• Folate deficiency
• Vitamin B12 deficiency
3. Hemolytic anemias-
• Autoimmune hemolytic anemia
• Sickle cell disease
• Thalassemia
• Glucose-6-phosphate deficiency
• Dehydrogenase deficiency

5. ERYTHROPOIESIS
• It is thought that white cells, red cells and platelets
are all derived from a common cell known as the
pluripotent stem cell found in the bone marrow.
• As these cells mature, they become committed to
a specific cell line.
• The red cells mature through the various stages,
during which time they synthesise haemoglobin.
• Reticulocytes are found in the peripheral
circulation for 24h before maturing into
erythrocytes.
• Reticulocytes are released into the peripheral
circulation prematurely during times of increased
erythropoiesis.

6. SIGNS AND SYMPTOMS:
• Tiredness or fatigue
• Pallor
• Fainting
• Exertional dyspnoea
• Tachycardia
• Palpitations
• Worsening angina
• Worsening cardiac failure
• Exacerbation of intermittent claudication (leg
cramps)

7. 1. IRON DEFICIENCY ANEMIA
• Iron deficiency anaemia is caused by deficiency of the element iron in body.
• Bone marrow needs iron to make hemoglobin. Without adequate iron, the body can’t
produce enough hemoglobin for red blood cells.
• Iron deficiency anaemia is the commonest form of anaemia worldwide and may be
present in up to 2 billion of the world's population.
• Inadequate dietary iron, impaired iron absorption, bleeding, or loss of body iron in the
urine are some of the cause of iron deficiency anaemia.
• Anaemia may result from a mismatch between the body's iron requirements and iron
absorption as iron bound to haem (found in red meat) is better absorbed than iron
found in green vegetables.
• The presence of phosphates and phytates in some vegetables leads to the formation of
unabsorbable iron complexes, whilst ascorbic acid increases the absorption of iron.

8. Causes-
1. Inadequate iron absorption
• Dietary deficiency
• Malabsorption
2. Increased physiological demand
Eg- pregnancy
3. Loss through bleeding/hemorrhage
Eg- menstrual bleeding, accident
Clinical manifestations-
1. Pale skin and mucus membranes
2. Painless glossitis
3. Angular stomatitis
4. Koilonychias (spoon-shaped nails)
5. Dysphagia (due to esophageal
web)
6. Pica (unusual cravings of ice, soil,
clay, paper)
7. Atrophic gastritis

9. • Prophylaxis of iron deficiency anaemia is given as
oral iron in the form of iron sulphate or fumarate
with folic acid in case of pregnant women having
poor iron diet, menorrhagia, after partial
gastrectomy, and in some low birth weight infants,
for example, premature twins.
• Oral iron in the ferrous form is cheap, safe and
effective in most patients and treatment can run up
to 6 month depending upon patient’s condition.
• The standard treatment is ferrous sulphate 200mg
two to three times a day. It typically takes between 1
and 2 weeks for the haemoglobin level to rise 1 g/dL.
TREATMENT:

10. 2. ANAEMIA OF CHRONIC DISEASE
• This is the second most common form of anaemia (after iron deficiency). It is
associated with a wide variety of inflammatory diseases including arthritis,
malignancies, inflammatory bowel disease, HIV and other infections.
• It is also called as anemia of inflammation
• In chronic kidney disease and chronic heart failure, the reduced renal blood flow
leads to a decreased production of erythropoietin.
• Due to this there is impaired response to erythropoietin and the inflammatory
cytokines which leads to a reduction in the availability of circulating iron.
• In malignancies, in addition to the anaemia of inflammation, the cytotoxic
treatments such as platinum-based therapies also decrease erythrocyte production
through their anti-proliferative effects on the bone marrow.

11. Pathophysiology-
• During infections, inflammation and cancer, the inflammatory cytokines, in articular
interleukin-6 released from macrophages, lead to an increased production of
hepcidin.
• Hepcidin, a peptide produced by hepatocytes, plays a key role in iron availability.
hepcidin causes-
• increased uptake of iron by hepatocytes
• reduced iron absorption
• reduced release of iron from macrophages.
Clinical manifestations-
Patients have the general symptoms of anaemia in addition to their symptoms of
the chronic inflammatory condition. The anaemia frequently leads to a reduced
quality of life for these patients.

13. TREATMENT-
• Oral iron therapy is not usually indicated despite the apparent reduced iron availability since
these patients have a functional iron deficiency rather than an actual iron deficiency; also,
the raised hepcidin levels reduce the oral absorption of iron.
• A number of patients with chronic renal failure appear to have a functional iron deficiency
that responds to intravenous iron in combination with erythropoietin analogues
• Patients with anaemia-associated inflammatory bowel disease or with rheumatoid arthritis
also respond to intravenous iron but,
• the use of intravenous iron in chronic inflammatory conditions is not generally
recommended because of an increased risk of infections and also possible increased risk of
acute cardiovascular events.
• Some patients with chronic disorders respond to erythropoietin analogues.
• Tocilizumab, the interleukin-6 antagonist monoclonal antibody licensed for use in
rheumatoid arthritis, has been shown to improve haemoglobin levels.

14. 3. SIDEROBLASTIC ANAEMIA
• Sideroblastic anaemias are a group of conditions that are diagnosed by finding ring sideroblasts in the bone
marrow.
• Sideroblasts are nucleated erythroblasts (precursors to mature red blood cells) with granules of iron
accumulated in the mitochondria surrounding the nucleus and is normally found in the bone marrow.
• There are hereditary, acquired or idiopathic. They also get activated by exposure to certain toxins or drugs.
• The hereditary forms are due to mutations in ALAS2 , ABCB7, GLRX5 and PSU1 genes but are rare
• the acquired forms are relatively common with as many as 30% of alcoholics admitted to hospital having
sideroblastic anaemia
• In this there is impaired haem synthesis, where the body has adequate iron stores but is unable to incorporate it
into haemoglobin
• Doses of chloramphenicol over 2 g a day invariably lead to sideroblasts. This is thought to be due to the
inhibition of mitochondrial protein synthesis.

15. Clinical manifestations-
• The hereditary forms typically develop in infancy or childhood. The anaemia can be
or mild (haemoglobin typically 4–10 g/dL).
• There may be splenomegaly, which can lead to mild thrombocytopenia.
• The idiopathic acquired forms tend to develop insidiously usually in middle age or later
is asymptomatic.
Treatment-
• In patients with the hereditary forms, large doses of pyridoxine (typically 100–200mg daily
or even up to 400mg) may reduce the severity of the anaemia.
• Patients with an acquired form occasionally respond to high dose pyridoxine, and a 2- to
month trial may be helpful in symptomatic patients.

16. • Haem arginate (licensed for use in porphyria) has been shown to increase the red cell count
and decrease the number of ring sideroblasts in some patients with acquired sideroblastic
anaemia
• Iron overload-
• Inevitably, some patients fail to respond to these treatments and frequent blood
transfusions are required.
• This leads to the complications of iron overload and sensitisation and the risk of blood-
borne virus transmission.
• The chelating agent desferrioxamine is given either by intravenous or by subcutaneous
infusion. It binds free iron and iron bound to ferritin.
• Therapy should be considered when the serum ferritin level reaches 1000μcg/L.
• There are two oral agents (desferiprone and deferasirox) licensed for iron overload.

17. 4. MEGALOBLASTIC ANEMIA
• The megaloblastic anemias are macrocytic anemias (raised MCV).
• There is an abnormality in the maturation of hematopoietic cells in the bone marrow.
• In addition to abnormal red cells, the white cells and platelets may be affected.
• The two major causes are folate deficiency and vitamin B12 deficiency.
• Pernicious anemia is a specific autoimmune disease that causes malabsorption of vitamin
B12 due to a lack of intrinsic factor.

18. FOLATE DEFECIENCY-
• The folate eventually acts as a coenzyme involved in a number of reactions
including DNA and RNA synthesis.
• Defective DNA synthesis mainly affects cells with a rapid turnover, for example,
gastro-intestinal cells and red blood cells, hence the sore tongue and anemia seen
in folate deficiency.
Clinical manifestation-
• Alcoholics and the elderly are particularly prone to nutritional deficiency.
• Serious malabsorption can occur in tropical sprue and coeliac disease.
• Reduced absorption is seen in Crohn's disease and following partial gastrectomy
jejunal resection.
• There is a physiological increase in folate utilization during pregnancy.
• There may be increased in utilization in various pathological state like chronic
hemolytic anemia.

19. • Treatment-
• Folate deficiency is usually managed by replacement therapy.
• The duration of the treatment depends on the cause of the deficiency.
• Changes in dietary habits or removal of any precipitating factor should also be
considered.
• usually 5-15 mg/day of folate is given for a period of 4 months.
• the folate requirement increases in pregnancy. Prophylaxis of folate in dose of 350-
500 micrograms daily is given with iron supplements starting before conception and
during initial 12 weeks of pregnancy.

20. • Vitamin B12 Deficiency-
• There are specific receptors in the distal ileum for the intrinsic factor-vitamin B12
complex.
• The vitamin B12 enters the ileal cell and is then transported through the blood
attached to transport proteins. Since intrinsic factor is only produced by the gastric
parietal cells, a total gastrectomy always leads to vitamin B12 deficiency.
• Approximately 10–15% of patients who have had a partial gastrectomy also develop
deficiency in years.
• Vitamin B12 is a coenzyme for the removal of a methyl group from methyl
tetrahydrofolate. Lack of vitamin B12 traps the folate as methyl tetrahydrofolate and
prevents DNA synthesis.

21. • Clinical manifestation-
• In addition to the macrocytosis, anisocytosis and poikilocytosis, there is often
thrombocytopenia.
• The spleen may be slightly enlarged and there may be a slight fever.
• Mild jaundice may be present due to the increased breakdown of haemoglobin
found in the abnormal red cells.
• The onset is slow and insidious, so patients often present late or are diagnosed
during other investigations.
• The feature that separates vitamin B12 deficiency from the other megaloblastic
anaemias is progressive neuropathy. It is symmetrical and affects the legs rather
than the arms.
• Patients notice a tingling in their feet and loss of vibration sense. Occasionally,
patients have muscle weakness, difficulty in walking or experience frequent falls.

22. Treatment-
• A definite diagnosis should be made before starting the treatment.
• standard treatment is hydroxocobalamin 1mg IM three times a week for 2
weeks then 1mg every 3 months.
• When there is neurological involvement a slight higher dose is recommended
1mg alternate days until no improvement is seen followed by 1mg every 2
months.
• In pernicious anemia 1mg daily oral and sublingual doses of cyanocobalamin is
given

23. 5. HEMOLYTIC ANEMIA
• In the haemolytic anaemias, there is a reduced life span of the erythrocytes. Anaemia
occurs when the rate of destruction of the erythrocytes exceeds their rate of
production.
• Patients with acute haemolytic anaemia commonly complain of malaise, fever,
abdominal pain, dark urine and jaundice.
• They have haemoglobulinaemia, hyperbilirubinaemia, reticulocytosis and increased
urobilinogen levels in the urine.
• Patients with chronic haemolytic anaemia also usually have splenomegaly.
• Their anaemia is usually normochromic and normocytic.
• Treatment include giving supplementation of folic acid to compensate for increased
demand and blood transfusion with chelating agent like desferioxamine to decrease
iron overload

24. Autoimmune hemolytic anemia-
• This include warm autoimmune hemolytic anemia and cold autoimmune
hemolytic anemia these result in production of igG antibody and igM
antibody causing destruction of red blood cells.
Treatment-
• It includes giving corticosteroids and azathioprine, cyclophosphamide to
unresponsive patient.

25. 6. SICKLE CELL ANEMIA
• Patient with sickle cell disease have a different form of hemoglobin called
hemoglobin S.
• HAEMOGLOBIN S has valine substituted for glutamic acid as the sixth amino acid in
the beta polypeptide chain compared with normal haemoglobin.
• the membrane of red cell containing haemoglobin S is damaged leads to intracellular
dehydration. In addition when patient blood is deoxygenated polymerization of
haemoglobin S occurs forming a semisolid gel .
• These two factors leads to formation of crescent shaped cell with reduced flexibility
thus can block microcirculation.

26. Clinical symptoms-
• Patients with severe variants of the disease have chronic anaemia, arthralgia,
anorexia, fatigue and splenomegaly.
• They have crises more frequently than patients with other variants of the
disease. A crisis can be precipitated by infection and fever, dehydration,
hypoxia or acidosis. A combination of these factors is sometimes present.
• The clinical manifestation of a crisis can vary with the most common being an
infarct crisis.
• Infarction of the long bones and larger joints or an infarction of a large organ,
for example, the liver, lungs or brain, may all occur.
• Severe pain is a common feature, depending on the site of the infarction.

27. • Treatment-
• penicillin5 250mg twice a day is usual for adults or erythromycin can be given in
who couldn’t tolerate penicillin. It is is given as a prophylactic or in case of presence
infection.
• Folic acid supplementation are given. hydroxycarbamide is effective and it may
incidence of crisis but it has a potential for cytotoxicity.
• Sickle cell crises require prompt and effective treatment. Removal of the trigger
hydration and effective pain relief are the mainstays of treatment. Appropriate
antibiotic therapy should be started at the first signs of infection. Strong opioids are
required for pain relief.

28. 7. THALASSEMIA
• It is an inherited blood disorder characterized by an abnormal production of
hemoglobin. because the disorder results in less hemoglobin and may also involve
fewer red blood cells, symptoms of thalassemia are like those we would expect to see
in a person with anemia, such as fatigue, pale skin, jaundice and slowed growth in
children.
• In β thalassaemias, there is a reduced or absent production of the globin β chain. This
leads to a relative excess of α chain which when unpaired become unstable and
precipitates in the red cell precursors.
• There is ineffective erythropoiesis and those mature cells that reach the circulation have
a shortened life span.

29. • In α thalassaemias, the pathology is slightly different. The deficiency of α chains
leads to an excess of γ or β chains.
• This time erythropoiesis is less affected, but the haemoglobin produced
(haemoglobin Bart's or Haemoglobin H) is unstable when the cells are in the
circulation and precipitates as the cells grow older.
• This leads to a shortened life span with the spleen trapping many of the cells.
Clinical manifestation-
• The anaemia causes erythropoietin production to increase and results in
expansion of the bone marrow.
• In severe disease, this causes bone deformity and growth retardation.
• The spleen is actively involved in removing the abnormal mature cells from the
circulation and becomes enlarged.