This document summarizes different types of anemia. It describes clinical features, signs, and classifications based on mean corpuscular volume. Specific types discussed in detail include iron deficiency anemia, anemia of chronic disease, sideroblastic anemia, thalassemia, sickle cell anemia, and megaloblastic anemia caused by vitamin B12 or folate deficiency. Investigations, underlying causes, and treatment approaches are provided for each major type of anemia.

1. Anemia

3. Anemia
● Clinical features-
○ Fatigue
○ Breathlessness,
○ Angina,
○ Intermittent claudication
○ Palpitations
● Signs-
○ Pallor
○ Tachycardia,
○ Systolic flow murmur,
○ Heart failure

5. Anemia
1. Hypochromic microcytic cells with low MCV
2. Normochromic normocytic cells with a normal MCV
3. Macrocytic cells with high MCV

7. Microcytic - MCV<80 fl
● Iron deficiency
● Thalassaemia
● Anaemia of chronic disease
● Sideroblastc anaemia

8. Macrocytic- MCV>96 fl
● Megaloblastic
○ Vitamin B12 deficiency
○ Folate deficiency
● Normoblastic
○ Alcohol
○ Increased reticulocytes
○ Haemolysis
○ Haemorrhage
○ Liver disease
○ Hypothyroidism
○ Drugs- Azathioprine

9. Normocytic cells- normal MCV
● Acute blood loss
● Anaemia of chronic disease
● Renal failure
● Autoimmune- rheumatoid disease
● Marrow infiltration- fibrosis
● Endocrine diseases
● Haemolytic anaemia

10. Microcytic Anaemia
Iron deficiency anemia
● Factors favouring Fe absorption
○ Haem iron
○ Fe2+ iron (ferrous iron)
○ Acids – HCl
○ Vitamin C
○ Solubilising agents- sugar, amino acids
○ Iron deficiency
○ Ineffective erythropoiesis
○ Pregnancy
○ Hereditary haemochromatosis
○ Increased expression of DMI & ferroportin

11. Iron deficiency anemia
● Factors reducing iron absorption
○ Inorganic Fe
○ Fe3+ (ferric iron)
○ Alkalis
○ Precipitating factors- phytate, phosphate
○ Reduced erythropoiesis
○ Infection
○ Tea
○ Increased hepcidin
○ Reduced DMTI, ferroportin

12. ● Features
○ Features of anaemia
○ Painless glossitis
○ Angular stomatitis
○ Brittle ridged spoon nails- koilonychias
○ Brittle hair
○ Dysphagia- Plummer-Vinson syndrome
○ Pica
○ Children- irritability, poor cognitive function, psychomotor disorder
Iron deficiency anemia

14. ● Causes Of iron deficiency
○ Increased loss- chronic blood loss, acute blood loss, therapeutic
phlebotomy
○ Reduced intake
○ Increased demand- infants, adolescents, pregnancy, lactation,
erythropoietin treatment
Iron deficiency anemia

16. ● Investigations
○ FBC- MCV<80 fl, hypochromic-<27 pg
○ Blood picture-
■ poikilocytosis(Increased cell shape)
■ anistocytosis(Increase cell size)
■ Target cells
○ Serum iron- low
○ Total iron binding capacity (TIBC)- high
○ Transferrin saturation- low- <19%
Iron deficiency anemia

17. Blood
picture in
iron
deficiency
anemia

19. ● Investigations
○ Serum ferritin- low- reflect s amount of stored iron (Serum ferritin- acute
phase reactant- level increases in presence of inflammation or malignant
disease)
○ Soluble transferrin receptors (Increase in iron deficiency; normal in
anaemia of chronic disease)
○ Bone marrow- erythroid hyperplasia &ridged normoblasts
○ Iron in bone marrow- absent
○ Iron in erythroblasts- absent
Iron deficiency anemia

20. ● Treatment of the course
● Iron to correct anaemia and replace iron stores
● Response monitored by reticulocyte count- 1g/dl/week increment
● Oral iron- most cases
○ Best- FeSO4 200 mg tds (60 mg elemental iron)
○ Side effects- Nausea, diarrhea, constipation
○ Take tablet with food
○ Reduce dose by using a preparation with less iron (Fe gluconate- 300mg
bd- only 70 mg elemental iron)
Iron deficiency anemia

21. ● Oral Fe should be given for long enough to correct Hb level & replenish iron
stores( may take 6 months)
● Parenteral iron- for those
○ who are intolerant to oral iron preparation
○ Severe malabsorption
○ Chronic disease
○ Replaces iron stores faster than oral iron-
○ haematological response-not quicker
○ IM injection of Fe sorbitol or IV infusion of Fe dextran
Iron deficiency anemia

22. Anaemia of chronic disease
● Tuberculosis
● Chronic inflammatory diseases- Crohn’s disease, SLE, malignancy,
Polymyalgia rheumatica
1. Reduced release of iron from bone marrow to developing erythroblasts
2. Inadequate erythropoietin response to anaemia
3. Decreased red cell survival

24. ● Investigations
○ Increased hepcidin
○ Serum iron- low
○ TIBC- low
○ Serum ferritin- normal or raised inflammatory process
○ Serum soluble transferrin receptor level- normal
○ Stainable iron present in bone marrow
○ Iron is not seen in developing erythroblasts
Anaemia of chronic disease

25. ● Treatment
○ Patient does not respond to iron therapy
○ Treat the underlying disease
○ Recombinant EPO used in anaemia of renal dx and pccasionally
inflammatory disease
Anaemia of chronic disease

26. Sideroblastic anaemia
● Inherited or acquired disorders characterized by refractory anaemia
● Hypochromic cells in peripheral blood
● Excess Fe & ring sideroblasts in bone marrow
● Presence of sideroblasts- diagnostic feature of sideroblastic anaemia
● Blood film- often dimorphic- ineffective synthesis- responsible for microcytic
hypochromic cells
● Disorder in haem synthesis- enzyme problems-Eg ALA synthase

27. ● Inherited
○ X-linked- transmitted by females
● Acquired
○ Myelodysplasia
○ Myeloproliferative disorder
○ Myeloid leukaemia
○ Drugs- isoniazid
○ Alcohol
○ Lead toxicity
○ Other disease- rheumatoid arthritis, Carcinoma, megaloblastic &
haemolytic anaemia
Sideroblastic anaemia

28. ● Investigations
○ MCV- low in inherited type but often increased in acquired type
○ Serum iron- increased
○ TIBC- normal
○ Serum ferritin- increased
○ Soluble transferrin receptors- normal or raised
○ Iron in bone marrow- present
○ Iron in erythroblasts -, ring forms
Sideroblastic anaemia

29. Ring sideroblasts

31. ● Treatment
○ Withdraw drugs and alcohol
○ Some cases respond to pyridoxine treatment
○ Treat with folic acid- to treat accompanying folate deficiency
Sideroblastic anaemia

32. Haemoglobin abnormalities
● Normal-
○ Hb A- α2β2—97%
○ Hb A2- α2β2- 2% of adult Hb
○ Hb F- α2γ2- normal Hb in fetus from 3rd to 9th months
○ Increase in β thalassaemia
○ Comprises <1% of Hb in adults

33. ● Abnormal chains-
○ H-β4- found in α thalassaemia- Biologically useless
○ Barts- γ4- comprises 100% of Hb in homozygous α thalassaemia-
Biologically useless
● Abnormal chain production-
○ S- α2β2S- substitution of valine for glutamic acid in position 6 of β chain.
○ C- α2β2C- substitution of lysine for glutamic acid in position 6 of β chain.
Haemoglobin abnormalities

34. Thalassaemia
● Autosomal recessive
● Normal balanced production of α and β chains
● α:β= 1:1
● Defective synthesis
● Imbalanced globin production- Precipitation of globin chains within red cells-
Resulting in ineffective erythropoiesis

35. ● No or reduced β chains
● Excess of α chains
● Precipitates in erythroblasts and red cells
● Raised HbA2, raised HbF, small amount of HbA
● β thalassaemia- point mutations
● α thalassaemia- gene deletions
β thalassaemia

36. ● Clinical features-
○ Thalassaemia minor (trait)- symptomless heterogenous carrier/ anaemia-
mild/absent
○ Thalassaemia intermedia- moderate anaemia(Hb:7-10g/dl)- rarely
requiring transfusions; not regularly
○ Thalassaemia major- severe anaemia requiring regular transfusions
■ Present in 1st year- failure to thrive & recurrent bacterial infections.
■ Severe anaemia in 3-6 months when switching from γ to β
■ Extramedullary haemopoiesis- hepatosplenomegaly and bone
expansion
β thalassaemia

37. Thalassaemic
face

39. ● Investigations
○ Skull X-ray- hair on end appearance
○ microcytic anemia
○ Target cells on the peripheral blood smear
○ detection of globin chain abnormalities demonstrated by haemoglobin
electrophoresis – old method
○ The recommended method currently is high performance liquid
chromatography (HPLC)
○ Genetic testing in selected cases
β thalassaemia

43. HPLC in beta
thalassemia
major

44. ● Treatment
○ Intermedia & Major- folic acid supplementation
○ Regular transfusions- Hb-10 g/dl
○ If more required- splenectomy
○ Iron overload- endocrine glands, liver, pancreas, myocardium
○ Iron chelation- desferrioxamine subcutaneous infusion
○ Ascorbic acid- increased urinary excretion
○ Sodium iron chelator- deferesirox, deferiprone
○ Bone marrow transplantation
β thalassaemia

45. α thalassaemia
● 4 gene deletions- α0_ _/_ _ _Hb Beits (γ4)-hydrops fetalis
● 3 gene deletions-α_/_ _Hb H(β4)- moderate anaemia, splenomegaly
● 2 gene deletions-_ _/αα_ -mild anaemia or _α/_α- Hb A- α thalasseamia trait
● 1 gene deletion- α_/αα or normal- α thalasseamia trait

46. Red cell membrane defects
Hereditary spherocytosis
● Autosomal dominant
● Unable to pass through splenic micro-circulation- shortened lifespan
● Clinical features-
○ Jaundice at birth; can be delayed
○ Anaemia, splenomegaly, ulcer on leg
○ As in any haemolytic anaemia

47. Hereditary spherocytosis
● Investigations-
○ Blood picture- spherocytes( round, lack of central pallor)
○ Osmotic fragility test-++
○ Direct antiglobulin (Coomb’s test)- (-)ve
● Treatment
○ Definitive management- splenectomy (app imm and lifelong penicillin
prophylaxis)
○ Following surgery- spherocytes present but RBC no longer destroyed
○ Folate prophylaxis

48. Hereditary spherocytosis - blood picture

50. Hereditary elliptocytosis
● Autosomal dominant

51. Metabolic disorders of RBC
G6PD deficiency
● X-linked recessive
● Female heterozygotes can also have clinical problems due to lyonisation
● Clinical features-
○ Acute drug induced haemolysis
○ Chronic haemolytic anaemia
○ Neonatal jaundice
○ Infection and acute illnesses will also precipitate
○ Gall stones

52. G6PD deficiency
● Investigations
○ Blood investigations- normal between attacks
○ During attack- blood film- irregular contracted cells
■ Bite cells
■ Blister cells
■ Heinz bodies
○ Reticulocytosis
○ G6PD assay

53. Blood picture
of G6PD
deficiency

56. ● Treatment
○ Stop offending agents
○ Treat underlying infection
○ Blood transfusion during crisis
○ Splenectomy- not usually helpful
G6PD deficiency

57. Pyruvate kinase deficiency
● Autosomal recessive
● Investigation
○ Blood picture- prickle cells
● Treatment
○ Blood transfusions
○ Splenectomy may improve clinical condition if frequent transfusions

58. Sickle cell Anaemia
● HbS- results from single base mutation- adenine to thymine or valine to
glutamic acid
● Homozygous- both genes abnormal- HbSS
● Heterozygous- sickle cell trait- HbAS
● HbF (α2γ2)- normal- so usually doesn’t until HbF decreases to adult level at 6
months
● Deoxygenated HbS - reduced RBC survival; impaired passage of cells via
microcirculation- obstruction of small vessels and tissue infarction.
● Homozygous HbSS- severe disease
● Combined heterozygous HbSS- intermediate symptoms
● Heterozygous HbAS- no symptoms

59. ● Clinical features
○ Vaso-occlusive crisis- Dactolytics
○ Anaemia- Hb- 6-8 g/dl
○ Splenic sequestration
○ Bone marrow aplasia
○ Avascular necrosis of hips
○ Osteomyeltis- Salmonella
○ Respiratory- Acute chest syndrome
○ Leg ulcers
○ Neurological- stroke, fits
Sickle cell Anaemia

61. ● Investigations
○ FBC- Hb low with elevated retic count
○ Blood picture- sickling
○ Hb electrophoresis
Sickle cell Anaemia

62. Sickle cell anemia - Blood picture

63. ● Management
○ Avoid precipitating factors
○ Acute painful attacks- supportive treatment with IV fluids, adequate
analgesics
○ Prophylaxis with penicillin 500 mg daily & vaccination for pneumococcal
& H.influenzae
○ Blood transfusion- should give for heart failure, transient ischaemic
attacks, stroke, acute chest syndrome, acute splenic sequestration,
aplastic crisis
○ Splenectomy
○ Bone marrow transplantation
Sickle cell Anaemia

64. Normocytic anaemia
● Anaemia of chronic disease
● Endocrine disorders- hypopituitarism, hypothyroidism, hypadrenalism
● Haematological diseases- aplastic anaemia and some haemolytic anaemias
● Acutely following blood loss

65. Macrocytic anaemia
● Can be megaloblastic, non-megaloblastic

66. Macrocytic Megaloblastic anaemia
● Presence of bone marrow erythroblasts with delayed nuclear maturation
because of defective DNA synthesis
● Nuclear chromatin- open stippled appearance
● Causes-
○ Vitamin B12 deficiency
○ Folic acid deficiency or abnormal folate metabolism
○ Defects in DNA synthesis
○ Myelodysplasia due to dyserythropoiesis

67. ● Haematological investigations
○ Anaemia with MCV>96 fl
○ Blood picture- oval macrocytes with hypersegmented neutrophils
○ If severe- pancytopenia
Macrocytic Megaloblastic anaemia

70. Vitamin B12 Deficiency
● Vitamin B12- synthesized by certain micro-organisms
● Human- ultimately depend on animal source
● Not usually destroyed by cooking
● Absorbed together with intrinsic factor in ileum
● Intrinsic factor-secreted by gastric parietal cells along with H+ ions
● Intrinsic Factor reduced pernicious anaemia- IF antibodies, parietal cell
antibodies
● B12 deficiency- S.methyl melanoic acid and homocysteine increase
● Schilling test – to look for the cause of B12 deficiency.

71. ● Causes
○ Nutritional- vegans
○ Malabsorption-
■ Gastric causes- Pernicious anaemia, Congenital IF deficiency,
Gastrectomy
■ Intestinal causes- Stagnant loop syndrome, Tropical sprue, Ileal
resection, Crohn, lymphoma, systemic sclerosis, fish tape worm
Vitamin B12 Deficiency

72. Folate deficiency-
● Only homocysteine increases.
● Folate found in green vegetables.
● Absorbed in duodenum and jejunum
● Lost in cooking

73. ● Causes of Folic acid deficiency
1. Nutritional
2. Malabsorption- Coeliac disease, legumes in food
3. Excess utilization
○ Physiological- Pregnancy, lactation
○ Pathological- haematological – hemolysis, malignancies,
inflammatory disease
4. Excess urinary loss- CCF
5. Drugs- anticonvulsants, cytotoxics
Folate deficiency-

74. Clinical effects of vitamin B12 and Folate deficiency
● Megaloblastic macrocytic anemia
● Pancytopenia
● Mild jaundice due to excess Hb breakdown due to ineffective erythropoiesis
● Glossitis, angular stomatitis
● Melanin pigmentation
● Decreased osteoblastic activity

76. Management
● B12 deficiency
○ Hydroxy-cobalamin 1000 µg IM- over the course of 3 weeks.( 6 doses
2/week)
○ Later every 3 weeks.
○ Clinical improvement within 48 hours.
○ Reticulocytosis- 2-3 days after starting treatment.
○ Peak 5-7 days.
○ Improvement of polyneuropathy within 6-12 months, but long standing
spinal cord damage- irreversible.
● Folic acid deficiency
○ Folic acid 5 mg- blood response like B12.

77. Macrocytosis without megaloblastic changes
● Alcohol excess.
● Liver disease ( inaddition to macrocytes also have target cells and
acanthocytes)
● Reticulocytosis.
● Hypothyroidism
● Some haematological disorders.
○ Aplastic anaemia.
○ Sideroblastic anaemia.
○ Pure red cell aplasia.

78. ● Drugs- cytotoxic- azathioprine
● Spurious- agglutinated red cells measured on red cell counters.
● Cold agglutinin due to red cells (MCV- normal with warming sample 370 C.
● Hyperglycaemia- RBC swelling
Macrocytosis without megaloblastic changes

79. Haemolytic anaemia
● Increased destruction of RBC (normal T1/2- 120 days)
● Haemolysis- compensatory increase in RBC production by bone marrow-
compensated haemolytic disease without anaemia- expanding volume of
active marrow and premature release of immaturecells- reticulocytes-
polychromasia

80. Hemolysis
● Increased RBC production
a. Increased reticulocytosis/polychromasia.
b. Erythroid hyperplasia of bone marrow
● Increased breakdown
a. Anaemia
b. Increased serum bilirubin.
c. Increased LDH, Serum potassium
d. Increased urobilinogen

82. ● Extravascular haemolysis
○ Main form
○ Macrophages in reticulo-endothelial system.
○ Particularly spleen.
○ Causes-
■ Haemoglobinopathies: sickle cell, thalassaemia
■ Hereditary spherocytosis
■ Haemolytic disease of newborn
■ Warm autoimmune haemolytic anaemia
Hemolysis

83. ● Intravascular haemolysis
○ Destruction within the circulation.
○ Hb is liberated
○ Initially bound to plasma haptoglobin
○ Soon haptoglobin become saturated
○ As haptoglobin becomes saturated Hb binds to albumin forming
methaemalbumin( detected by Schumm’s test)
○ Free Hb is excreted in urine as haemogloinuria, haemosiderinuria
Hemolysis

84. ● Intravascular haemolysis.
○ Haemoglobinaemia and haemoglobinuria.
○ Haemosiderinuria (iron storage protein in spundeposit of urine).
○ Methaemalbuminaemia (detected spectrometrically- Schumm’s test).
○ Very low or absent haptoglobin.
Hemolysis

85. ● Causes
○ Mismatched blood transfusion.
○ G6PD deficiency and oxidant stress.
○ Red cell fragmentation syndrome- mechanical heart valves, DIC, TTP,
HUS
○ Cold autoimmune haemolytic anaemia.
○ Some drug and infection induced haemolytic anaemia.
○ Paroxysmal Nocturnal Haemoglobinuria (PNH)- March haemoglobinuria.
Hemolysis

86. Autoimmune haemolytic anaemia
● Divided into “warm” and “cold” types according to at what temperature the
antibodies best cause haemolysis.
● AIHA is characterized by a positive direct antiglobulin test.(Coombs’ test)

89. Warm acquired immune hemolytic anaemia(Warm
AIHA)
● Type of antibody- IgG
● Cause haemolysis best at body temperature and tends to occur in
extravascular sites Eg- spleen
● Causes- idiopathic, auto immune- SLE, lymphoma, CLL, drugs- methyldopa
● Investigations : Those of hemolytic anaemia
Spherocytes on the blood film

90. WAHA -
Blood
picture

91. ● Mx- treat cause
○ blood transfusions if necessary
○ steroids
○ immunosuppressive drugs –azathoprine, cyclophosphamide IVIg
○ splenectomy is only a final option if there is poor response to the medical
management
Warm acquired immune hemolytic anaemia(Warm
AIHA)

92. Cold acquired immune hemolytic anaemia(Cold
AIHA)
● IgM
● Causes haemolysis best at 4 degree celcius
● Haemolysis is mediated by complements and more commonly intravascular
● May have Raynaud’s and acrocyanosis
● Causes-
○ idiopathic
○ infections- mycoplasma, EBV
○ Neoplasia- lymphoma

93. ● Investigations
○ Those of hemolytic anaemia
○ less spherocytes
○ cold agglutination test
● Management
○ treat cause
○ respond less well to steroids
○ keep warm
Cold acquired immune hemolytic anaemia(Cold
AIHA)

95. Non immune haemolytic anaemia
1.Paroxysmal nocturnal haemoglobinuria
● Clinical features-
○ intravascular haemolysis
○ venous thrombosis- BuddChiari syndrome, mesenteric thrombosis,
cerebral thrombosis
○ haemoglobinuria

96. Paroxysmal nocturnal haemoglobinuria
● Clinical features
○ Haemolysis may be precipitated by infection ,therapy or surgery
○ Characteristically urine voided at night and in the morning on waking is
dark in colour
○ Severe case – all urine samples are dark
○ Urine Fe loss- Fe deficiency anaemia

97. ● Investigations
○ Intravascular haemolysis
○ Flow cytometrical analysis of RBC with Anti CD55(replaced Ham test)
○ BM-sometime hypoplasia
Paroxysmal nocturnal haemoglobinuria

98. ● Treatment
○ Supportive- blood product replacement
○ Eculizumab
○ Long term anticoagulation if recurrent thrombosis
○ BM failure – immune suppression
○ Stem cell transplantation
● PNH→ Aplastic anaemia
Acute leukaemia
Paroxysmal nocturnal haemoglobinuria

99. 2. Mechanical haemolytic anaemia
● Physical trauma→fragmented RBC
● Damaged artificial heart valves
● March haemoglobinuria
● MAHA- malignant hypertension, Eclampsia, haemolytic uraemic
syndrome,TTP,DIC,Vasculitis

101. Pancytopenia
1. Aplastic anaemia
● pancytopenia with hypocellularity (aplasia ) oh bone marrow
● Inherited or aquired
● Decrease in the no of pluripotent stem cells
● Failure in one cell line also occurs
● Evolution into myelodysplasia, AML, PNH also occurs

102. Aplastic anaemia
● Clinical features-
○ pancytopenia
○ Bleeding manifestations
○ Lymphadenopathy & hepatosplenomegaly –rare

103. ● Aetiologies
○ Congenital- Fanconi’s anaemia (AR)
○ Cytotoxic drugs
○ Chloramphenicol, trimethoprim, penicillamine, carbamazepine,
carbimazole ( causes agranulocytosis and pancytopenia), AZT, gold,
tolbutamide
○ Exposure to chemicals – benzene, toluene
○ Ionizing radiation
○ PNH
○ Infections-HIV, Hepatitis,TB, EBV, erythrovirus
Aplastic anaemia

104. ● Investigations
○ Pancytopenia with virtual absence of reticulocytes
○ Hypocellular/ Aplastic marrow
Aplastic anaemia

105. Bone marrow biopsy - Aplastic anaemia

106. ● Treatment
○ Supportive treatment-RBC, plt
○ Avoiding infections, broad spectrum antibiotics
○ Remove the cause
○ Course-remission/progression
○ Specific treatment- Anti lymphocyte globulin, Ciclosporin, Stem cell
transplantation
Aplastic anaemia

107. Pancytopenia
2.Haematological malignancies –Leukaemia, lymphoma,multiple myeloma
3.Secondary infiltration of bone marrow-Malignancies, TB
4.megaloblastic anaemia
5.Hypersplenism
6.PNH
7.Sepsis
8.SLE

108. Iron deficiency Anaemia of
chronic disease
Thalassaemia
trait (α or β)
Sideroblastic
anaemia
MCV Reduced Low normal or
normal
Very low for
degree of
anaemia
Low in inherited
type but often
raised in
acquired type
Serum iron Reduced Reduced Normal Raised
Serum TIBC Raised Reduced Normal Normal
Serum ferritin Reduced Normal or raised Normal Raised
Serum soluble
transfer receptors
Increased Normal Normal or
raised
Normal or raised
Iron in marrow Absent Present Present Present
Iron in
erythroblasts
Absent Absent or
reduced
Present Ring forms

109. Thank you