This document provides an overview of hematopoiesis, erythropoiesis, and anemia. It discusses where blood cell formation occurs, the lifespan and production rate of red blood cells, and how hypoxia stimulates erythropoietin production. It defines anemia, lists global and country prevalence data, and compensatory mechanisms. It describes classifications of anemia including morphological and etiological, and covers causes such as blood loss, bone marrow disorders, nutritional deficiencies, and hemolytic anemias. Laboratory evaluation of anemia and peripheral blood smear findings are also summarized.

2. • Overview of Hematopoiesis.
• Overview of Erythropoiesis.
• Introduction to Anaemia.
• Classification and Pathophysiology of different
causes of Anaemia.
• Laboratory Investigation of Anaemia.
• References.

3. OVERVIEW OF HEMATOPOESIS
• In the human embryo, the yolk sac is the main site of
haematopoiesis in the first few weeks of gestation.
• About the third month the liver and spleen are the main sites
of blood cell formation and continue to do so until about the
second week after birth.
• Haematopoiesis commences in the bone marrow by 4th and
5th month and becomes fully active by 7th and 8th month so
that at birth practically all the bones contain active marrow.
• During normal childhood and adult life bone marrow is the
only source of new blood cells.

4. OVERVIEW OF ERYTHROPOIESIS
• Erythropoiesis is the
process by which
RBC/Erythrocytes are
produced
• Last about 7 days.
• Erythrocytes are
continously produced in
the red bone marrow at a
rate of about 2 million per
second in healthy adult
• Life span 100-120 days
• Production also stimulated
by ↓ O₂ in circulation.

5. EPO STIMULATION AT THE KIDNEYS
DUE TO HYPOXIA

6. Introduction to Anemia
Anemia
 (An-without,emia-blood) is a decrease in the RBC
count, hemoglobin and/or Hematocrit values
resulting in a lower ability for the blood to carry
oxygen to body tissues .
 Anemia is not a disease but a sign of some
underlying disease.

8. • Globally, anaemia affects 1.62 billion people, which
corresponds to 24.8% of the population. The
highest prevalence is in preschool-age children
(47.4%), and the lowest prevalence is in men
(12.7%). However, the population group with the
greatest number of individuals affected is non-
pregnant women (468.4 million).
• Tanzania- Prevalence of anaemia among women of
reproductive age (15 – 49) was 37.20 (2016),
children underfive 55.20.

9. COMPENSATORY MECHANISMS

10. CLASSIFICATION AND CAUSES
OF ANAEMIA
I. Morphologic Classification
1. Macrocytic anemia
2. Microcytic hypochromic anemia
3. Normochromic normocytic anemia
II.Etiologic Classification
1. Impaired RBC production
2. Excessive destruction
3. Blood loss

11. Inadequate RBC Production
1. Abnormal bone marrow
i. Aplastic anemia
ii. Myelophthisis : Myelofibrosis, Leukemia,
Cancer metastasis
2. Nutrition/Essential factors deficiency
i. Deficiency anemia : Fe, Vit. B12, Folic acid, etc
ii. Anemia in renal disease : Erythropoietin
3. Stimulation factor deficiency
i. Anemia in chronic disease
ii. Anemia in hypopituitarism
iii. Anemia in hypothyroidism

12. 1. Macrocytic Anemia
• MCV > 94
• MCHC > 31
1. Megaloblastic dyspoiesis
1. Vit. B12 deficiency : Pernicious anemia
2. Folic acid deficiency : Nutritional megaloblas-
• tic anemia, Sprue, Other malabsorption
1. Inborn errors of metabolism : Orotic aciduria,
etc.
2. Abnormal DNA synthesis : Chemotherapy,
Anticonvulsant, Oral contraceptives

13. Vitamin B12 Deficiency and Mechanism

15. Pathophysiology of megaloblastic anemia.

16. 2. Microcytic Hypochromic Anemia
• MCV < 80, MCHC< 31
1. Fe deficiency anemia : Chronic blood loss,
Inadequate diet, Malabsorption, Increased
demand, etc.
2. Abnormal globin synthesis : Thalassemia with or
without Hemoglobinopathies
3. Abnormal porphyrin and heme synthesis :
Pyridoxine responsive anemia, etc.
4. Other abnormal Fe metabolism :

18. 3.Normocytic Normochromic Anemia
82 - 92
> 30
MCV
MCHC
1. Blood loss
1. Increased plasma volume : Pregnancy, Overhydration
2. Hemolytic anemia : depend on each cause
3. Hypoplastic marrow : Aplastic anemia, RBC aplasia
4. Infiltrate BM : Leukemia, Multiple myeloma,
Myelofibrosis, etc.
5. Abnormal endocrine : Hypothyroidism, Adrenal
insufficiency, etc.
6. Kidney disease / Liver disease / Cirrhosis

19. 2. Anemia Of Blood Loss
1. Acute blood loss
i. Accident, GI bleeding
2. Chronic blood loss :
i. Hypermenorrhea
ii. Parasitic infestation
The anemia is normocytic
and normochromic
• In acute blood loss, the
immediate threat to the
patient is hypovolemia
(shock) rather than anemia.
• If the patient survives,
hemodilution begins at once
and achieves its full effect
within 2 to 3 days,
unmasking the extent of the
red cell loss.

20. 3.Hemolytic anemia
1. Intracorpuscular defect
1. Membrane : Hereditary spherocytosis
Hereditary ovalocytosis, etc.
1. Enzyme deficiency : G-6PD deficiency.
2. Hemoglobin abnormality:-eg. Sickle cell
disease, Thalassemia,

21. 3.Hemolytic anemia cont…
1. Extracorpuscular defect
1. Mechanical : March hemolytic anemia
MAHA (Microangiopathic
Hemolytic Anemia)
1. Chemical/Physical eg.various drugs
2. Infection : Clostridium perfringers
3. Antibodies : Hemolytic transfusion
reaction,SLE
4. Hypersplenism

22. Hemolytic Anemia,cont..
• These are anemia which occur due to
increased/ Premature breakdown of RBC.
• Causes hereditary and acquired disorders
• Hemolysis occurs at two sites
i. Intravascular
ii. Extravascular.

23. Intravascular
- Hemolysis occurs within systemic circulation.
- Hemoglobin is released into plasma.
- Hemoglobin is lost through kidneys or catabolized
in the liver.
Extravascular
- Trapping of red cells in spleen or liver sinuses.
- Lyses of trapped red cells.
- Release of lysed hemoglobin and catabolism within
the sequestering organ.

24. G-6-PD deficiency
• FUNCTION OF G6PD
• Regenerates NADPH, allowing regeneration of
glutathione
• Protects against oxidative stress
• Lack of G6PD leads to hemolysis during
oxidative stress- infection.
• Oxidative stress leads to Heinz body
formation, extravascular hemolysis

25. Cont…

26. Drug-Induced Acute Hemolysis
•
•
•
•
•
•
•
•
•
Drugs that have been linked to G6PD:
Primaquine (an antimalarial)
Sulphonamide antibiotics
Sulphones (e.g. dapsone, used against leprosy)
Other sulphur-containing drugs:
Glibenclamide (an anti-diabetic drug)
Nitrofurantoin (an antibiotic often used for urinary tract
infections)
Vitamin K analogues
Several others
Can cause a hemolytic crisis in G6PD deficient infants

27. SIKLE CELL ANEMIA
• This is a severe hereditary form of anemia
in which a mutated form of haemoglobulin
distorts the red blood cells into a crescent
shape at low oxygen concetration.
• It is the genetic condition where by the
glutamic acid is replaced by valine in the 6
position of the 146amino acid of beta
chain of hemoglobin.

29. IMMUNE HEMOLYTIC ANEMIA
General Principles
• All require antigen-antibody reactions
• Types of reactions dependent on:
– Class of Antibody
– Number & Spacing of antigenic sites on cell
– Availability of complement
– Environmental Temperature
– Functional status of reticuloendothelial system
• Manifestations
– Intravascular hemolysis
– Extravascular hemolysis

30. Are caused by AB production by the body against its
own red cells.
Divided into 
1) warmIgG alone. Bind at> 37c
2) cold Usually IgM. Bind to red cell at <37c
Immune haemolytic anaemias

33. • SYMPTOMS
–Fatigue
–Headaches
–lightheadedness
–Breathlessness
–Angina
–Intermittent claudication
–Palpitation

34. • SIGNS
–Pallor
–Tachycardia
–Systolic murmurs
–Signs of Cardiac failure
–Papilloedema-retinal hemorrhage
(rare)

35. • Good history and physical examination
• Any history of medical problems that could
cause anemia?
– Sickle cell Disease?
– Thalassemia?
– Renal Disease?
– Hereditary Spherocytosis?

36. Laboratory Evaluation
• Initial Testing
-CBC with differential(include RBC indices)
-Reticulocyte count
-Peripheral blood smear
• Bleeding
-Serial HCT or HGB
• Iron Deficiency
-Iron studies

37. Laboratory Evaluation cont…
• Hemolysis
-Serum LDH,
-Indirect bilirubin
-haptoglobin
-coombs test and coagulation studies
• Bone Marrow Examination
• Others -directed by clinical indication
-Hemoglobin electrophoresis
-B12/folate level

39. THE RED CELL POPULATION
• The red cell population is defined by
1.Qualitative parameters
-Volume of packed cells : the hematocrit
-Hemoglobin concentration
-Red cell concentration per unit volume
2.Qualitative parameters
-Mean corpusular volume,MCV
-Mean corpusular hemoglobin,MCH
-Mean corpusular heamoglobin concentration,MCHC

40. •
Chemistry
Hyperbilirubinemia,predominantly unconjugated bilirubin
due to breakdown of heme ring by reticuloendothelial cells
in the liver.
Elevated lactate dehydrogenase(LDH): released into the
plasma from destroyed cells.
Hemoglobinemia: excess free hemoglobin level in the
blood plasma due to increases in hemolysis esp.
intravascular hemolysis: levels of 10-20 mg/dl gives
plasma amber color and 50-100 gm/dl reddish color.

41. Hemoglobinuria: red-brown color of urine
due to free hemoglobin and
methamoglobin.
Decreased Heptaglobin level: it is a alpha-2-
globin produced in the liver. It binds free
hemoglobin thus level is reduced in hemolysis.
Hemosidrinuria: it reflects extensive
hemolysis for a prolonged period of time.
When hemoglobin is filtered by nephron,
proximal tubular cells metabolize hemoglobin
and iron accumulate in the cells. Cells then
exfoliate in the urine and iron can be detected
by Prussian blue reaction.

42. Peripheral Blood Smear

43. Peripheral Blood and Bone Marrow Smear

44. • Robbins Textbook 7th and 8th Editions
• Harsh Mohan textbook of pathology
6thEdition
• B. L. Mtinangi – Anaemia Work up
• http://www.irondisorders.org
• https://emedicine.mediscape.co/article/202
333-overview