Haematology: Approach to Anaemia 

1. DISORDERS CAUSING ANAEMIA

1.1 Principle of Diagnosis
1.1.1 Recognise specific/nonspecific manifestations
1.1.2 Clinical evaluation of severity
1.1.3 Clinical inference of likely cause(s)
1.2 Principles of Management
1.2.1 Confirmation of underlying aetiology
1.2.2 Significance of PBF changes
1.2.3 Indications of urgent/chronic transfusion requirement
1.2.4 Principles of managing reversible causes

Definition of anaemia
 Anaemia = reduction in the oxygen-transporting capacity of blood, usually because of a
reduction of the total circulating RBC mass

Classification of anaemia by pathogenesis

Anaemia

Blood loss Increased destruction Decreased

(haemolytic anaemias) production

- Acute
- Chronic Intrinsic Extrinsic 1. Aplastic anaemia
(classified abnormalities causes 2. Bone marrow
under iron suppression
deficiency) 3. Myelophthisis
4. Defective DNA
synthesis
Hereditary Acquired - folate def
1. Antibody mediated
- Vit B12 def
- transfusion
5. Defective Hb
- Rh dz of newborn
synthesis
1. Membrane defects Memb defect - drug induced
- iron deficiency
- spherocytosis - paroxysmal - SLE
- globin deficiency
- elliptocytosis nocturnal - idiopathic
(thalassemia)
2. Enzyme defects Hburia 2. Mechanical trauma
- pyruvate kinase - artificial valves
- G6PD deficiency - complement
- glutathione synthase - microangiopathic
3. Hb synthesis defects hemolytic anaemia
- globin deficiency 3. Infections
(thalassemia) - malaria
- globin structural
abnormality
(sickle cell)
Pathogenesis concepts in anaemia
 Anaemia results in decreased tissue oxygen tension
 This triggers increased erythropoietin production
- Exception is anaemia of chronic renal failure, in which the cells that produce erythropoietin
are lost
 Results in compensatory hyperplasia of erythroid precursors in the bone marrow and appearance of
extramedullary hematopoiesis in secondary hematopoietic organs (spleen, liver)
 Increased numbers of newly formed RBCs (reticulocytes) are released into the circulation
- Exception is aplastic anaemia, which is characterised by reticulocytopenia

Classification of anaemia by red cell morphology (more useful clinically)

Anaemia

Peripheral blood film

Microcytic Macrocytic
MCV < 80 fl Normocytic MCV > 95 fl
Normal MCV
1. Iron deficiency
- reduced intake Megaloblastic Non-
1. Uremia megaloblastic
- decreased 2. Connective tissue dz
absorption 3. Aplastic anaemia
- increased - drugs 1. B12 deficiency 1. Alcohol
demand eg. preg 4. Marrow infiltration - Pernicious 2. Hypothyroid
- chronic blood 5. Myelofibrosis - Post gastrectomy 3. Liver disease
loss 6. Haemolytic anaemia
2. Thalassemia - Vegans
7. Anaemia of chronic dz - Malabsorption
3. Sideroblastic 8. Acute blood loss
4. Anaemia of 2. Folate
chronic disease deficiency
- Poor intake
- Pregnancy
- FBC - Malignancy, chr
- FBC - Reticulocyte count inflammation
- PT PTT, INR - UECr - Drugs: valproate
- Serum iron, serum - Hemolytic screen
ferritin, total iron - BMAT
binding capacity - FBC
- Fecal OB - Reticulocyte count
- OGD/colonoscopy - Serum Vit B12 and
- Hb electrophoresis serum and red cell
in susceptible folate levels
ethnic groups - Thyroid function tests
- BMAT - Liver function tests
- Antibodies against
gastric parietal cells or
intrinsic factor
- OGD
 Subjective RBC indices (seen on peripheral blood film)
- RBC size and shape
- RBC colour
 Objective RBC indices (measured and reported in full blood count)
- Mean cell volume (MCV): average volume of a RBC (femtolitres)
- Mean cell haemoglobin (MCH): average mass of haemoglobin per RBC (picograms)
- Mean cell haemoglobin concentration (MCHC): average conc of Hb in a given vol of packed
cells (g/dL)
- Red cell distribution width (RDW): co-efficient of variation in RBC volume

Clinical features of anaemia

 History
- Ethnic origin: impt in thalassemia
- When was the last normal blood test
- How was anaemia diagnosed
- Symptoms of anaemia: fatigue, fainting, breathlessness, angina, intermittent claudication,
palpitations, visual disturbances cos of retinal hemorrhages
- Severity: effort tolerance, required bld transfusions
Questions related to etiology
- Weight loss: malignancy, chronic disease
- Diet: deficiencies, alcohol
- GIT blood loss eg. PR bleed, maelena, haemetemesis, change in stool habit/tenesmus, epigastric
pain relieved by food
- Menstrual blood loss: duration, length of periods, any clots, number of pads used
- Drug history eg. NSAIDs, bone marrow suppressive drugs, exposure to benzene
- Surgical history: gastrectomy, artificial heart valves
- Family history: inherited conditions
- Travel history: malaria-endemic countries

Physical Examination
General condition
- pallor
- jaundice  haemolytic anaemias
- breathless
- nutritional status
- receiving any transfusions  indicates severity
- low bp, sweaty  hypovolemic shock
Hands
- koilonychia, brittle nails  iron deficiency
- clubbing  infective endocarditis
- tachycardia
Eye
- Conjunctival pallor
- Jaundice  Haemolytic or pernicious anaemia (due to ineffective erythropoiesis)
Mouth
- Glossitis  vit B12 deficiency
- Angular stomatitis  severe malnutrition, iron deficiency
- Ulcers: neutropenia
Others
- Chipmunk facies, frontal bossing  thalassemia
- LN: neck, axilla, inguinal  metastases, lymphoproliferative disorders, hemato malignancy
- Skin: bruising  bone marrow depression, leukemia, aplastic anaemia
- Chest scars  artificial heart valves
- CVS: tachycardia, bounding pulse, systolic flow murmur at the apex
 - Abdomen: splenomegaly (infection, haemolytic anaemia), any other masses (malignancy)
- PR: hemorrhoids, tumour
- Bone deformities: thalassemia major
- Legs ulcers: seen in sickle cell anaemia

Investigations for MCHC or NCNC anaemia

 FBC: - Hb <14g/dL in males, <12g/dl in females
- MCV, MCH
- WBC and plt: if decreased, anaemia is part of a more general haematological problem eg.
leukaemia, aplastic anaemia
 Reticulocyte count: elevated in acute blood loss, hemolysis [normal count is 0.5-2.5%]
decreased in iron deficiency
 PBF: - spherocytes
- teardrop cells: myelofibrosis
- target cells: post splenectomy, thalassemia, iron deficiency
- pencil cells: iron deficiency
- sickle cells: sickle cell anaemia
- helmet cells: post splenectomy, traumatic haemolytic anaemia
 Iron studies: - low serum iron, low serum ferritin, high TIBC: iron deficiency
- low serum iron, high serum ferritin, low TIBC: anaemia of chronic disease
* ferritin is an acute phase reactant, raised in inflammation

Interpreting Plasma Iron Studies

Iron TIBC Ferritin
Fe deficiency   
Anaemia of Chronic dz   
Chronic haemolysis   
Haemchromatosis  /N 
Pregnancy   N
Sideroblastic anaemia  N 

 Hemolytic screen: - reticulocyte count

- haptoglobin: decreased in hemolysis [haptoglobins bind to free Hb and are
removed by the spleen]
- LDH
- Coomb’s test: immune hemolysis
- Bilirubin
 UECr
 PT/PTT
 Hb electrophoresis
 Stool occult blood
 OGD/Colonoscopy: look for source of bleeding, malignancy
 BMAT
a) Aspiration: cells aspirated through a needle, spread on a slide, takes 1-2 hours
- details of individual cells visible
- myeloid:erythroid ratio can be calculated
- presence of cells of secondary malignancies
- other tests include iron staining, cytogenetics, microbiological culture
b) Trephine: requires fixation in formalin, includes solid core of bone and marrow, 1-7 days
- cannot see individual cell detail
- cellularity of the marrow, overall architecture, fibrosis
- other tests: immunological staining
- can be done when aspiration gives a ‘dry tap’
Investigations for macrocytic anaemia
 FBC: - Hb <14g/dL in males, <12g/dl in females
- MCV, MCH
 Reticulocyte count: decreased in B12, folate deficiency
 PBF: - oval macrocytes in megaloblastic anaemia
- hypersegmented neutrophils (>6 lobes) in megaloblastic anaemia
 Serum Vit B12, serum and red cell folate levels
 Thyroid function tests
 Liver function tests
 Antibodies against gastric parietal cells or intrinsic factor
 OGD
 BMAT

Indications for blood transfusion

- Acute blood loss > 20% of total blood volume, regardless of Hct (Normal bld vol = 70ml/kg in
adults)
- No blood loss, but Hct <30% and risk of ischemia (history of IHD or stroke)
or signs/symptoms of acute anaemia - syncope
- tachycardia
- angina/dyspnea
- SpO2 < 90%
- change in mental status
- Hb <7g/dL