Approach to Anaemia

Sameh S El-Atawy
2009
P ro po rtio n (% ) o f popula tio n c o vered by a na em ia preva lenc e
s urveys (na tio na l o r s ub-na tio na l) betw een 1993 a nd 2005
– Source: WHO VMNIS

P o pula tio n g ro up P reva lenc e P o pula tio n

N um ber
P erc ent 95% C I 95% C I
(m illio ns )
Preschool-age children 47.4 45.7-49.1 293 283-303
School-age children 25.4 19.9-30.9 305 238-371
Pregnant women 41.8 39.9-43.8 56 54-59
Non-pregnant women 30.2 28.7-31.6 468 446-491
Men 12.7 8.6-16.9 260 175-345
Elderly 23.9 18.3-29.4 164 126-202

T o ta l po pula tio n 24.8 22.9-26.7 1620 1500-1740

E s tim a ted preva lenc e (% ) o f a na em ia (1990-1995) by W H O
R eg io n ba s ed o n H a em o g lo bin c o nc entra tio n
– Source: WHO VMNIS

P o pula tio n
W H O R eg io n P o pula tio n a ffec ted by a na em ia
(m illio ns )
Number
Prevalence %
(millions)
Africa 535 244 46
The Americas 751 141 19
South East Asia 1364 779 57
Europe 860 84 10
Eastern
408 184 45
Mediterranean
Western Pacific 1574 598 38
T o ta l 5491 2030 37
N um ber o f c o untries c a teg orized by public hea lth s ig nific a nc e
o f a na em ia
– Source: WHO VMNIS

P reg na nt
P res c ho o l-a g e N o n-preg na nt
P ublic hea lth w o m en
c hildren w o m en
pro blem Number of Number of
Number of
countries countries
countries
None 2 0  1
Mild 40 33 59
Moderate 81 91 78
Severe 69 68 54
 Definition
A haemoglobin concentration lower than
normal for the age and sex of the person.
Lower limits of normal (at sea level):
● Adult male 13,5g/dl
● Adult female 11,5 g/dl
● Newborn to 3 months 15g/dl
● Three months to puberty 11g/dl
 Definition
Comparison with the results of previous full blood count is
important. As a rule of thumb, a drop of 10% or more in the
haemoglobin indicates that something is wrong and needs
investigation.
 Classification
Morphologic Classification:
● Hypochromic microcytic anaemia
● Macrocytic Anaemia
● Normochromic normocytic anaemia
 Classification
● Hypochromic microcytic anaemia
– Iron deficiency
– Anaemia of chronic disease
– Thalassaemia
– Sideroblastic anaemia
– Lead poisoning
 Classification
● Macrocytic Anaemia
– Megaloblastic anaemia (B12 or folate
deficiency)
– Liver disease
– Alcohol
– Hypothyroidism
 Classification
● Normochromic normocytic anaemia
– Acute blood loss
– Renal failure
– Anaemia of chronic disease
 Aetiology
● Increased Red Cell Loss
– Blood loss
– Haemolysis
● Intracorpuscular
– Membrane disorder (incl PNH)
– Enzymopathy
– Haemoglobinopathy
● Extracorpuscular
– Immune
– Mechanical
– Infections
 Aetiology
● Decreased Red Cell Production
– Abnormalities of the stem cells
● Aplastic Anaemia
– Defective DNA Synthesis
● Megaloblastic anaemia
– Defective Haemoglobin Synthesis
● Iron deficiency
● Thalassaemia
 Aetiology
● Decreased Red Cell Production
– Displacement of normal haemopoietic
progenitors
● Haematologic malignancies
● Metastatic tumours
● Fibrosis
– Decreased erythropoietin
● Renal failure
 Aetiology
● Decreased Red Cell Production
– Multi-factorial
● Anaemia of chronic disease
● HIV infection.
 Aetiology in the Tropics
● Malnutrition is extremely prevalent and is
the commonest etiology.
● Parasitic diseases can cause:
– Direct RBC destruction (eg. Malaria)
– RBC loss - Hypersplenism (eg. Kala Azar)
– Loss of whole blood (eg. Ankylostoma)
– Malabsorption (eg. Diphyllobothrium spp.)
– Anaemia of chronic disease
 Aetiology in the Tropics
● HIV infection, CRF, and Hepatitis are more
common as causes of anemia in the
tropics.
● Tropical Sprue is a regional etiology.
● Thalassemia is commoner in the middle
east than elsewhere.
● Sickle-cell anemia is commoner in western
Africa (due to evolutionary selection in
malaria-endemic areas).
 Findings
● Symptoms related to the anaemia:
– Pallor
– Exercise intolerance and easy fatigue,
weakness and lethargy
– Shortness of breath
– Syncope
– Palpitations and headaches.
– Older patients may have cardiac failure,
intermittent claudication or confusion.
 Findings
● Symptoms which may suggest an
underlying cause
– Jaundice
– Blood loss or bleeding tendency
– Chronic disease
– Pregnancy
– Family history
 Findings
● Pallor
● Splenomegaly (haemolysis)
● Jaundice (haemolysis, liver disease, megaloblastic
anaemia)
● Koilonychia (iron deficiency)
● Beefy red tongue (megaloblastic anaemia)
● Painless glossitis, angular cheilosis (iron deficiency)
● Neuropathy (vit B12 deficiency)
● Purpura (accompanying thrombocytopenia)
 Findings
● Full blood count
– Confirms anaemia and shows any accompanying
leukopenia or thrombocytopenia if present, as
well as indicating microcytosis or normocytosis
or macrocytosis
● Reticulocyte count
– An increased reticulocyte count indicates a
marrow response to the anaemia and is
suggestive of either haemorrhage or
haemolysis.
– A low reticulocyte count indicates a production
problem in the bone marrow.
 Findings
● Biochemical Screen for Haemolysis
– (If clinically suspected it is appropriate to screen
for haemolysis as a baseline)
– LDH is increased
– Serum Haptoglobin is decreased
– Serum bilirubin (unconjugated) and urine
urobilinogen are increased
● Examination of the peripheral blood smear
– Morphology of the red cells may give clues as to
the cause of the anaemia.
 Findings
– Pencil cells and occasional target cells
suggets iron deficiency.
– A raised Red Cell Count is suggestive of
Thalassaemia Trait.
– Marked increase in target cells, occasional
fragments and basophilic stippling are
features of Thalassaemia intermedia and
Thalassaemia major
– Basophilic stippling is a feature of Lead
poisoning.
 Findings
– Polychromasia indicates a reticulocytosis.
– Oval macrocytes, red cell fragments and
hypersegmented neutrophils are features
of megaloblastic anaemia. Leukopenia
and thrombocytopenia may also be
present.
– Round macrocytes are found in the non-
megaloblastic macrocytic anaemias.
 Findings
– Dysplasia of red cells, white cell or
platelets may suggest myelodysplastic
syndromes.
– In aplastic anaemia, the red cells may be
macrocytic. In this setting a
pancytopenia is present but features of
megaloblastosis and dysplasia are
absent.
Microcytic Hypochromic A.
Serum Ferritin

Low High

TIBC (Transferrin)
Iron Deficiency Anaemia

High Normal/Low
Microcytic Hypochromic A.
Chronic Disease

Yes Hb Electrophoresis

Anaemia of Chronic Disease

Abnormal Exclude alpha Thalassemia

Confirm Beta Thalassemia Exclude Lead Poisoning

Congenital Sideroblastic Anaemia BM Biopsy

 Macrocytic A.
Reticulocyte Count

Normal/Low High

Exclude Liver Disease Serum B12 level and

Hypothyroidism Red Cell Folate level
Alcoholism

Haemorrage Normal Low

Haemolysis
Treated Deficiency
Megaloblastic Anaemia
None
BM Biopsy
Myelodysplasia
Aplastic Anaemia Failed Treatment
Normocytic Normochromic A.
Exclude Acute Blood Loss

Examine PB Smear

Features of Haemolysis Haemolytic Anaemia

Findings of B12/Folate deficiency

Haemolysis
Leukoerythroblastic Reaction Severe Infection

No Findings

Renal Failure BM Biopsy

HIV Infection Infiltration
Chronic Disease Aplastic Anaemia
 Haemolytic A.
Coombs Test

Negative Positive

Monospecific Coombs Test

Examine PB Smear

Warm AIHA Cold AIHA Paroxysmal

Cold
Haemogolbinuria
 Haemolytic A.
Negative Coombs Test

Examine PB Smear DIC, TTP, HUS,

Vasculitis,
Malignant Hypertension
Fragments

Spherocytes Hereditary Spherocytosis

Clostridium infections
Sickle Cells
G6PD deficiency
Bite Cells Unstable Hb
No Findings
Enzyme Assays
Hams Test (PNH)
Flow Cytometry
 Haemolytic A.
Positive Coombs Test

Monospecific Coombs Test

SLE, Drugs,
Warm AIHA Delayed Transfusion Reaction,
(IgG+) Lymphoproliferative Disorder

Infectious Mononucleosis,
Cold AIHA Mycoplasma,
(IgG-) Lymphoproliferative Disorder

PNH

Donald Landsteiner Test

 Alternative Approach
Low Haemoglobin

Increased Blood Volume Normal Blood Volume

Reticulocytosis
No Anaemia

Recent Blood Loss ? Haemolytic

Anaemia ?

Blood Indices and Anaemia of

Peripheral Smear Iron Deficiency
Alternative Approach (contd)
Blood Indices and Peripheral Smear

Abnormal Normal

Urea, Creatinine,
HIV ?

BM Biopsy Anaemia of CRF,

AIDS

Iron Deficiency, Normal: Anaemia of

Marrow Infiltration, Chronic Disease
Aplasia, etc.
Alternative Approach (contd)
Abnormal Blood Indices and Peripheral Smear

Macrocytosis Microcytosis
Hypothyroidism,
Liver Disease ?
s. ferritin, TIBC
B12, Folic Acid

High Low
Low Normal

Megaloblastic BM Biopsy Thalassemia Iron Deficiency

Anaemia (HbA2, HbF)
 Haemolytic Anaemia

Coombs Test

Negative Positive
Malaria, Splenomegaly,
Septicaemia, Burns,.. ?

Autoimmune,
drugs,..
Hb electrophoresis,
sucrose lysis, acid haemolysis,
osmotic fragility, G6PD
and pyruvate kinase levels. Spherocytosis,
Sickle cell anaemia,
Favism, PNH, etc.
 Summary
● Anemia is an extremely common finding.
● Anemia varies in aetiology according to the region, age,
onset, etc.
● Worldwide, nutritional anemia is the commonest.
● An etiologic diagnosis of anemia is vital to proper
management.
● History, blood indices, reticulocytosis, peripheral smear,
Coombs test, etc are necessary to reach an etiologic
diagnosis; collaboration with a reliable laboratory is vital.
● The vast majority of cases can be diagnosed before
having to do a bone marrow biopsy.
Thank You