The document discusses different types of anemias including their causes, mechanisms, and characteristics. It covers iron deficiency anemia, the most common type caused by lack of iron intake or increased loss. It also discusses megaloblastic anemias caused by vitamin B12 or folate deficiencies which result in large immature red blood cells. Thalassemia syndromes are genetic disorders that cause decreased hemoglobin production. The document also examines normocytic anemias and anemias associated with chronic diseases and infections.

1. TYPES OF ANAEMIAS
PRESENTED BY
MISS TASMIA ZEB

2. ANEMIAS CAUSES
The main causes (often interacting) of anaemia in tropical countries are:
● Malnutrition, associated particularly with:
• Iron deficiency anaemia. Iron deficiency is the commonest form of
anaemia and a major health problem in tropical countries.
• Folate deficiency (less commonly, vitamin B12 deficiency)
• Protein deficiency

3. TO BE CONTIN................
• Parasitic, bacterial, and viral infections, particularly:
• Falciparum malaria, hyperreactive malaria, splenomegaly Malaria is
the commonest cause of death from anaemia in young children in
tropical countries.
• Hookworm infection Tuberculosis and other chronic infections
• HIV disease/AIDS and treatment with antiretroviral drugs such as
zidovudine .
• Visceral leishmaniasis
• African trypanosomiasis
• Less commonly, parvovirus B19 infection and viral haemorrhagic
fever diseases.

4. CONTI......................
 Inherited haemoglobinopathies, including: –
• Sickle cell disease.
• Thalassaemia syndromes.
Glucose 6 phosphate dehydrogenase (G6PD) deficiency.
Obstetrical complications causing abnormal blood loss.

5. MECHANISIM OF ANAEMIA
BLOOD LOSS
● Acute bleeding, e.g. from wounds, surgical, ectopic pregnancy, placenta praevia
● Chronic blood loss, e.g. hookworm infection, schistosomiasis, gastrointestinal bleeding,
menorrhagia
DECREASED RED CELL PRODUCTION
● Lack of essential nutrients, e.g. deficiencies of iron, folate, vitamin B12, protein
● Depressed bone marrow activity, e.g. anaemias associated with chronic disease such as
tuberculosis, HIV disease, chronic nephritis, chronic hepatitis, connective tissue disorders,
malignant disease, leukaemias
● Due to drugs, chemicals, ionizing radiation, some viruses
● Thalassaemia syndromes

6. • INCREASED RED CELL DESTRUCTION (HAEMOLYSIS)
● Inherited haemolytic anaemias
 Haemoglobinopathies, e.g. sickle cell diseases, thalassaemia
syndromes.
 Red cell enzyme deficiencies, e.g. G6PD deficiency, pyruvate kinase
deficiency.
 Red cell membrane defects e.g. hereditary spherocytosis

7. ● Non-immune acquired haemolytic anaemias:
Infections, e.g. malaria, African trypanosomiasis, meningococcal septicaemia, C. perfringens infection, bartonellosis
– Pre-eclampsia and HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count)
– Conditions which cause disseminated intravascular coagulation (DIC) – Haemolytic uraemic syndrome
– Hypersplenism and splenomegaly, e.g. visceral leishmaniasis, hyper-reactive malaria, splenomegaly, myelofibrosis
– Burns
– Venomous snake and spider bites
– Chemicals, oxidant drugs, local herbal remedies
– Paroxysmal nocturnal haemoglobi

8. ● Immune acquired haemolytic anaemias (DAT positive):
• Haemolytic disease of the newborn
• Haemolytic blood transfusion reaction
• Warm reactive autoantibody, e.g. drug-induced chronic lymphatic
leukaemia, lymphoma, systemic lupus erythematosus
• Cold reactive autoantibody, e.g. M. pneumonia infection, lymphoma –
Paroxysmal cold haemoglobinuria

9. IRON DEFICIENCY ANAEMIA
• Iron deficiency anaemia
Iron is needed to produce the haem component of haemoglobin and a
small amount is needed to produce muscle myoglobin and
cytochromes (respiratory enzymes). Insufficient iron for haemoglobin
production leads to iron deficiency anaemia.

10. Causes of iron deficiency
Causes of iron deficiency
● Intake of iron is insufficient or the iron in the diet is in a form which is not
easily absorbed, e.g. non-haem iron of plant origin (in contrast, haem iron in
meat is easily absorbed). Also, diets in tropical countries are often high in
substances which inhibit the absorption of non-haem iron e.g. phytic acid in
grain fibres. Ascorbic acid in the diet helps to absorb non-haem iron.
● Increased loss of iron due to chronic blood loss as occurs in severe hookworm
infection, schistosomiasis, trichuriasis, gastrointestinal bleeding, menorrhagia.
● Malabsorption of iron as in intestinal malabsorptive disease, e.g. acute post-
infective malabsorption (PIM).
● Increased demand for iron as occurs in the early years of life and during
pregnancy.
Note: Iron deficiency causes a microcytic hypochromic anaemia

11. DIAGNOSIS
Following investigations are to be performed for diagnosing a case of
anaemia:
• Estimation of Haemoglobin (Hb).
• Estimation of Total Red Blood Cell Count (TRBC).
• Estimation of Haematocrit (Hct) or Packed Cell Volume (PCV).
• Calculation of absolute values.
• Examination of peripheral blood film.
• Reticulocyte count
• After determining the morphological type of anaemia, the patient is
further investigated to determine the cause of it

12. Other tests to investigate microcytic hypochromic
anaemia
• Other tests to investigate microcytic hypochromic anaemia
●Serum ferritin1
●Serum iron
●TIB
●Bone marrow iron
●Haemoglobin electrophoresis

13. THALASSAEMIA SYNDROMES
• THALASSAEMIA SYNDROMES
• Thalassaemia syndromes are inherited disorders caused by a reduction in the
rate of synthesis of alpha or beta haemoglobin chains.
• Alpha thalassaemias are caused by defective synthesis of chains. Beta
thalassaemias are caused by defective synthesis of chains.
• Significant imbalance in the synthesis of alpha and beta chains leads to:
Inadequate haemoglobin production. The MCV and MCH are low and the red
cells appear microcytic and hypochromic.
• Accumulation of free uncombined globin chains in normoblasts and red cells,
causing the destruction of red cell precursors in the bone marrow (ineffective
erythropoiesis) and red cell destruction by the spleen.

14. contin...........
• The clinical severity of alpha and beta thalassaemia syndromes
depends on the thalassaemia genes inherited, and in some
syndromes, the interaction of thalassaemia genes with abnormal
haemoglobin genes, e.g. HbS, HbE, HbC. The terms thalassaemia
major, intermedia, and minor are used to describe the severity of
disease.

15. MACROCYTIC ANAEMIA
• MACROCYTIC ANAEMIA Caused by:
Megaloblastic changes:
• Folate deficiency
• Vitamin B12 deficiency
Non-megaloblastic changes:
• Liver disease
• Alcoholism
• Haemolytic anaemia (associated with raised reticulocyte count)

16. Folate deficiency and vitamin B12 deficiency
Folate deficiency and vitamin B12 deficiency
Folate (folic acid) and vitamin B12 (cobalamins) are essential for DNA
(deoxyribonucleic acid) synthesis and are therefore needed by all
dividing cells in the body, particularly haematopoietic cells in the
bone marrow. Deficiencies lead to nuclear maturation being blocked
which prevents growing cells from dividing normally (cytoplasmic
maturation is not blocked). Many precursor cells die in the bone
marrow.
Vitamin B12 is also needed to prevent degenerative changes in the
nervous system.

17. Causes of folate deficiency:
Causes of folate deficiency
● Low intake of folate in the diet (often seasonal) or more commonly, folate is inadequate
because it is destroyed when food is overheated e.g. prolonged boiling of folate rich foods
such as green vegetables, sweet potatoes, yams, plantain, peppers, meat, fish.
● Intestinal malabsorptive disease, e.g. PIM and malabsorption associated with Giardia
lamblia and Strongyloides infections. Folate absorption is also depressed in diseases such
as tuberculosis and severe pneumonia.
● High demands for folate in infancy (particularly premature infants) and childhood, during
pregnancy, and in diseases such as sickle cell disease, malaria and other haemolytic
anaemias. Also in malignant disease.
● Drugs which interfere with folate utilization, e.g. pyrimethamine, trimethoprim and
antifolate cytotoxic drugs.

18. Causes of vitamin B12 deficiency Deficiency
Causes of vitamin B12 deficiency
Deficiency Due to low intake is rare. Vitamin B12 is synthesized by bacteria and is therefore
available in foods of animal origin. The body’s daily requirement for vitamin B12 is low.
Intrinsic factor (IF), a protein secreted by parietal cells in the stomach, is essential for the
absorption of vitamin B12. The main causes of vitamin B12 deficiency are:
● Lack of IF due to gastric disease such as autoimmune gastritis (pernicious anaemia)
which damages parietal cells and prevents IF secretion.
● Intestinal malabsorption due to PIM, chronic Giardia lamblia infection and severe
enteritis.
● Rare causes include cyanide poisoning from the incorrect preparation of cassava, and
infection with the fish tapeworm Diphyllobothrium latum (competes with host for vitamin
B12).

19. Note:
Folate and vitamin B12 deficiencies cause megaloblastic
changes in the bone marrow with a macrocytic anaemia and
in the advanced stage, pancytopenia (low numbers of red
cells, granulocytes, and platelets)
megaloblastic anemias are the result of medications or
inherited defects in the transport/metabolism of vitamin B12
or folic acid. Pernicious anemia is a type of megaloblastic
anemia in which the body isn't able to absorb vitamin B12
due to a lack of intrinsic factor in stomach secretions.

20. NORMOCHROMIC ANAEMIA
NORMOCHROMIC ANAEMIA
In a normocytic normochromic anaemia the red cells appear
normocytic and normochromic in a stained blood film and the MCHC;
MCV and MCH are normal.
 A normocytic normochromic anaemia may be found in:
• Acute blood loss
• Anaemia of chronic disease
• Aplastic anaemia

21. Anaemia of chronic disease
Anaemia of chronic disease Infections, malignancies, and chronic
inflammatory conditions , can cause normocytic normochromic or
microcytic hypochromic anaemia. Examination of a blood film for RBC
and leukocyte abnormalities is helpful, particularly in identifying
anaemia due to infection. Other tests to perform will depend on the
clinical findings.

22. Anaemias of infections and chronic disease
Anaemias of infections and chronic disease
• The following diseases are associated with anaemia:
 Infectious diseases
• Tuberculosis
• Pneumonia
• Pulmonary abscess
• Bacterial endocarditis
• Pelvic inflammatory disease
• Osteomyelitis HIV disease
 Non-infectious diseases
• Malignant disease
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Other connective tissue disorder

23. Aplastic anaemia:
Aplastic anaemia
• In aplastic anaemia there is a reduction in the number of red cells,
neutrophils, and platelets in the peripheral blood (pancytopenia), low
reticulocyte count, and decrease in blood-forming tissue in the bone marrow.
• Causes of acquired aplastic anaemia include drugs (e.g. chloramphenicol,
nonsteroidal anti-inflammatory drugs, cytotoxic drugs),
• viral infection (e.g. hepatitis viruses, Epstein-Barr virus) and ionizing radiation.
• Note: Other causes of pancytopenia include HIV disease, visceral
leishmaniasis, leukaemia, multiple myeloma, myelofibrosis, megaloblastic
anaemia, myelodysplastic disorders, parvovirus, and splenomegaly.

24. Haemolytic anaemias:
Haemolytic anaemias
Haemolytic anaemias are characterized by a falling haemoglobin,
jaundice, dark urine, increasing reticulocytosis (when there is effective
erythropoiesis) and usually splenomegaly.
In tropical countries haemolytic anaemias due to both:
 intrinsic causes (hereditary disorders)
extrinsic causes (acquired disorders)
both are important causes of ill health and premature death,
particularly those due to serious thalassaemia syndromes, diseases due
to abnormal haemoglobins, and haemolysis associated with malaria,
other parasitic infections, and bacterial infections.

25. Extravascular haemolysis:
In most haemolytic anaemias, haemolysis is extravascular, i.e. red cells are
destroyed by macrophages in the spleen, liver, and bone marrow. Providing liver
function is normal there is an increase in serum unconjugated bilirubin and
urine urobilinogen (urine bilirubin is negative).
Intravascular haemolysis: This is when red cells are destroyed in blood vessels
and haemoglobin is released into the circulation e.g. haemolysis following
incompatible blood transfusion, malaria haemoglobinuria, paroxysmal
nocturnal haemoglobinuria (rare complement-mediated haemolysis), or when
there is red cell membrane damage due to antibody and complement, toxic
chemicals or drugs. Laboratory findings in intravascular haemolysis include
reduced or absent serum haptoglobins, haemoglobinaemia (free haemoglobin
in the plasma), presence of methaemalbumin in plasma, and haemoglobin and
haemosiderin in urine

26. • Investigation of haemolytic anaemia,
the serum/plasma appears yellow due to increased bilirubin. A clinical
history and examination of a blood film can help to establish the
possible cause of a haemolytic anaemia and indicate the need for
further tests to confirm the diagnosis and assist in treatment and
genetic counselling (when a hereditary condition is suspected).
Laboratory staff should be aware of the local distribution of hereditary
disorders, e.g. haemoglobinopathies and the common causes of
acquired haemolytic anaemias.

27. ● Blood film findings:
• Red cells are usually normochromic. Microcytic hypochromic cells are found in thalassaemia and when there is
accompanying iron deficiency anaemia.
• Polychromasia (indicating reticulocytosis) is present in most haemolytic anaemias when there is an effective
erythropoietic response.
• In malaria, reticulocytes are only slightly increased in the early stages of infection. Anaemia in malaria is
multifactorial. It includes bone marrow suppression in addition to haemolysis.
• Sickle cells which are typically seen in sickle cell anaemia, HbSC disease, HbS thalassaemia .
• Malaria parasites in red cells, often with malaria pigment in leukocytes.
• Trypanosomes in blood film .Acute African trypanosomiasis is a cause of rapidly progressive haemolytic anaemia.
• Spherocytes which may be seen in C. perfringens septicaemia, serious burns, bartonellosis, in G6PD deficiency
(during haemolytic crisis), acquired immune haemolytic anaemia due to warm reactive autoantibody, ABO
haemolytic disease of the newborn, in haemolytic uraemic syndrome (rare) and typically in hereditary
spherocytosis (inherited red cell membrane disorder).
• Nucleated red cells, which can be seen in sickle cell disease,
• thalassaemia major and intermedia disease ,C. perfringens septicaemia, haemolytic disease of the newborn, and
autoimmune haemolytic anaemias (due to warm reacting antibody).
• Red cell fragments (schistocytes) which are seen when red cells are damaged, e.g. in burns, disseminated
intravascular coagulation, pre-eclampsia, and in microangiopathic

28. conti..............
• anaemia associated with Gram negative septicaemia and less commonly,
artificial heart valves.
• ‘Bite’ and ghost cells which can be seen during a haemolytic crisis caused by
G6PD deficiency (Heinz bodies may also be seen in a reticulocyte preparation,
• Target cells which are seen particularly in thalassaemia syndromes , sickle cell
disease, HbC disease, liver disease.
• Basophilic stippling, which is most frequently seen in thalassaemia
syndromes .
• Marked red cell agglutination (clumping due to antibody-coating) of red cells
which is seen in immune haemolytic anaemia due to cold reacting
autoantibody (unless blood sample is kept at 37C).
• Bartonella organisms in red cells, causing Oroya fever .

29. Other tests to investigate haemolytic anaemia
• Reticulocyte count, see To assess erythropoietic
●Sickle cell slide test or If sickle cell disease is solubility test,
●Haemoglobin To demonstrate HbS, electrophoresis, HbC or other abnormal To detect raised HbA2 and HbF if
thalassaemia syndrome is suspected .
●G6PD screening test,
●Direct antiglobulin test If immune haemolytic (DAT) using broad anaemia is suspected. spectrum serum, see Positive
DAT is found
• Warm reacting autoantibody (IgG, complement)
• Cold reacting autoantibody (IgM)
• Drug induced autoantibody, e.g. methyl dopa, penicillin, cephalothin quinidine, chloramphenicol
• Haemolytic disease of the newborn
• Incompatible haemolytic blood transfusion reaction

30. contin.............
●Test to detect RBC membrane defects: If red cell membrane
disorderis suspected, e.g. hereditary spherocytosis, paroxysmal
nocturnal haemoglobinuria.
– Autohaemolysis test
– Osmotic fragility
– Glycerol lysis test
– Ham’s test