Nyambura Kariuki

Initial diagnostic approach

What is the severity of the anaemia?
What is the cause of the anaemia?

Detailed history and physical examination

Minimum of essential laboratory tests
CLASSIFICATION
Aetiological classification
OF ANAEMIA
A. Anaemia due to impaired red cell production
B. Disorders of erythroid maturation and ineffective
erythropoeisis
C. Haemolytic Anaemia
D. Anaemia due to blood loss

Morphological classification
A.Microcytic Anaemia
B. Macrocytic Anaemia
C. Normocytic Anaemia
Aetiological classification of anaemia
A. Anaemia due to impaired red cell production

1. Marrow failure
a) Aplastic anaemia: Congenital or Acquired
b) Pure red cell aplasia: Congenital or Acquired
c) Marrow replacement (Myelophthisic anaemia)
- Malignancies e.g leukaemia, lymphoma, metastatic carcinoma
and solid tumours
- Infections
- Storage disorders
- Myelofibrosis
- Osteopetrosis
d) Pancreatic insufficiency – marrow hypoplasia syndrome
 Aetiological classification of anaemia
A. Anaemia due to impaired red cell production

2. Impaired erythropoietin production

a) Chronic renal disease
b)Hypothyroidism, hypopituitarism
c) Chronic inflammation
d)Protein malnutrition
e) Haemoglobin mutants with decreased affinity for oxygen
 Aetiological classification of anaemia
B. Disorders of erythroid maturation and ineffective
erythropoeisis

1. Abnormalities of cytoplasmic maturation

a) Iron deficiency
b)Sideroblastic anaemia
c) Thalassaemic syndromes
d)Lead poisoning
 Aetiological classification of anaemia
B. Disorders of erythroid maturation and ineffective erythropoeisis

2. Abnormalities of nuclear maturation

a) Folic acid deficiency
b) Vitamin B12 deficiency
c) Thiamine-responsive megaloblastic anaemia
d) Folate metabolism hereditary abnormalities
e) Orotic aciduria
3. Congenital dyserythropoietic anaemia

4. Erythropoeitic protoporphyria
 Aetiological classification of anaemia
C. Haemolytic Anaemia
Abnormality intrinsic to red cells
1. Defects in red cell membrane
Hereditary spherocytosis
Hereditary elliptocytosis
2. Defects in haemoglobin
Quantitative: Thalassaemias
Qualitative: Sickle Cell Disease;
Haemoglobin D, E, or C disease
3. Defects in enzymes
Glucose-6-phosphate dehydrogenase deficiency
Pyruvate kinase deficiency
 Aetiological classification of anaemia
C. Haemolytic anaemia
Abnormality extrinsic to red cells
1. Immune haemolytic anaemias
Autoimmunue
Alloimmune
Drug-induced
2. Mechanical haemolytic anaemia
Microangiopathic
Cardiac
March haemoglobinuria
3. Direct action of physical, chemical, or infectious agents
4. Hypersplenism
D. Anaemia due to blood loss
Important causes of anaemia in Africa
Nutritional deficiency: Iron, folate, less commonly
vitamin B12
Infections: Tuberculosis, malaria, kala-azar, HIV
infection/AIDS, hookworm
Inherited anaemias: Sickle cell disorders,
thalassaemias, glucose-6-phosphate dehydrogenase
deficiency
Blood loss: Obstetrical problems
Microcytic anaemia
Iron deficiency
Anaemia of chronic disease
Sideroblastic anaemia
Lead poisoning
Thalassaemia α and β
Macrocytic anaemia
Megaloblastic: vitamin B12 or folate deficiency

Non-megaloblastic: alcohol, liver disease,

myelodysplasia, aplastic anaemia, myxoedema,
myeloma, reticulocytosis, neonatal, cytotoxic drugs,
smoking, pregnancy
Normocytic normochromic anaemia
Many haemolytic anaemia
Anaemia of chronic disease (some cases)
After acute blood loss
Renal disease
Mixed deficiencies
Bone marrow failure e.g. Post-chemotherapy,
infiltration by carcinoma
Initial diagnostic approach
What is the severity of the anaemia?
What is the cause of the anaemia?

Detailed history and physical examination

Minimum of essential laboratory tests
 Inital Tests
FBC + PBF + Reticulocyte Count
Haemoglobin, Haematocrit concentration, Red cell
indices, Reticulocyte count, White cell count &
differential , Platelet count, Peripheral blood smear ,
Coomb’s test
Stool for ova, cyst, occult blood
Bone marrow aspirate - morphology, iron stores
Hb electrophoresis,
 Serum ferritin concentration, TIBC, serum vitamin
B12 , RBC folate
Causes of reticulocytosis
•Acute blood loss
•Haemolytic anaemia
•Response to therapy in nutritional anaemias

Causes of reticulocytopaenia
•Iron deficiency anaemia
•Anaemia of chronic disease
•Aplastic anaemia
•Anaemia due to marrow infiltration
Haemolytic Anaemia
1. Increased RBC breakdown
Serum bilirubin raised, unconjugated, bound to
albumin
Urine urobilinogen increased
Faecal stercobilinogen increased
Serum haptoglobins absent – become saturated with
hb & complex removed by RE cells
 Haemolytic Anaemia
2. Features of increased red cell production
Reticulocytosis
Bone marrow erythroid hyperplasia
 Haemolytic Anaemia
3. Damaged cells
 Morphology – microspherocytes, elliptocytes,
fragments
 Osmotic fragility, autohaemolysis
 RBC survival shortened - 51Cr labelling studies sites of
destruction
Intravascular haemolysis
Haemoglobinaemia & Haemoglobinuria

Haemosidenuria( iron storage protein in the spun

deposit of urine)

Methaemalbuminaemia ( detected spectrometrically

by Schumm’s test)
Warm autoimmune haemolytic anaemia
Typical of an extravascular haemolytic anaemia
Spherocytosis
DAT positive due to IgG, IgG & complement or IgA
on the cells
Autoantibodies on cell surface & in serum best
detected at 37oC
Cold autoimmune haemolytic anaemia
Autoantibody attaches to RBC mainly in peripheral circulation
where blood temperature is cooled

Usually IgM antibody – binds to RBC be at 4oC

IgM efficient at binding complement

Complement alone usually detected on RBC, antibody having

eluted off RBCin warmer parts of circulation

Extravascular & intravascular haemolysis

Paroxysmal nocturnal haemoglobinuria
Deficient synthesis of anchor( GPI) glycosylphosphatidylinositol

GPI attaches several surface proteins to the cell membrane

RBC rendered sensitive to lysis by complement resulting in

Chronic intravascular haemolysis
Recurrent thromboses of large veins
Bone marrow aplasia

Flow cytometry shows loss of expression of GPI-linked proteins

Hypochromic Anaemia
Transferrin receptor is shed from cells into
plasma

Serum Transferrin receptor is increased in

IDA
Increased erythropoeisis
Hypochromic anaemia
RBC indices & blood film
Bone marrow iron stores
Total Iron Binding Capacity
Serum transferrin receptor
Serum ferritin
Erythroblast iron
Haemoglobin electrophoresis
Vitamin B12 deficiency
Serum Methylmalonic acid
Serum Homocysteine

More sensitive than Vitamin B12 assay in detection of

Vitamin B12 deficiency