MICROCYTIC ANAEMIA

OBJECTIVES

• At the end of this lecture, you will be able to:

• Describe Anaemia and its different types.
• Discuss the different types of microcytic
anaemia.
 ANAEMIA
• This is defined as a reduction in the haemoglobin
concentration of the blood below normal for age and
sex .
• Although normal values can vary between
laboratories, typical values would be less than 135 g/L
in adult males and less than 115 g/L in adult females.
• From the age of 2 years to puberty, less than 110 g/L
indicates anaemia.
• As newborn infants have a high haemoglobin level,
140 g/L is taken as the lower limit at birth.
 CAUSES
• Alterations in total circulating plasma volume as well as of total
circulating haemoglobin mass determine the haemoglobin concentration.
• Reduction in plasma volume (as in dehydration) may mask anaemia or
even cause (apparent,pseudo) polycythaemia, conversely, an increase in
plasma volume (as with splenomegaly or pregnancy) may cause anaemia
even with a normal total circulating red cell and haemoglobin mass.
• After acute major blood loss, anaemia is not immediately apparent
because the total blood volume is reduced. It takes up to a day for the
plasma volume to be replaced and so for the degree of anaemia to
become apparent .
• Regeneration of red cells and haemoglobin mass takes substantially
longer.
• The initial clinical features of major blood loss are therefore a result of
reduction in blood volume rather than of anaemia.
 SIGNS AND SYMPTOMS
• Symptoms
• If the patient does have symptoms these are usually shortness of breath,
particularly on exertion, weakness, lethargy, palpitation and headaches.
• In older subjects, symptoms of cardiac failure,angina pectoris or intermittent
claudication or confusion may be present.
• Visual disturbances because of retinal haemorrhages may complicate very
severe anaemia, particularly of rapid onset.

• Signs
• These may be divided into general and specific.
• General signs
• include pallor of mucous membranes or nail beds, which occurs if the
haemoglobin level is less than 90 g/L.
• A hyperdynamic circulation may be present with tachycardia, a bounding
pulse, cardiomegaly and a systolic flow murmur especially at the apex.
• Particularly in the elderly, features of congestive heart failure may be
present.
• Specific signs:
• Are associated with particular types of anaemia, e.g.
koilonychia (spoon nails) with iron deficiency, jaundice
with haemolytic or megaloblastic anaemias, leg ulcers
with sickle cell and other haemolytic anaemias, bone
deformities with thalassaemia major.

• The association of features of anaemia with excess

infections or spontaneous bruising suggest that
neutropenia or thrombocytopenia may be present,
possibly as a result of bone marrow failure.
 CLASSIFICATION AND LABORATORY FINDINGS IN ANAEMIA

• Red cell indices

• The most useful classification is that based on red cell indices and
divides the anaemia into microcytic, normocytic and macrocytic .
• As well as suggesting the nature of the primary defect, this approach
may also indicate an underlying abnormality before overt anaemia
has developed.
• In two common physiological situations, the mean corpuscular
volume (MCV) may be outside the normal adult range.
• In the newborn for a few weeks the MCV is high but in infancy it is
low (e.g. 70 fL at 1 year of age) and rises slowly throughout
childhood to the normal adult range.
• In normal pregnancy there is a slight rise in MCV, even in the absence
of other causes of macrocytosis (e.g. folate deficiency).
TYPES OF ANAEMIA
 CONT…
• Microcytosis is a term used to describe red blood cells that are smaller than
normal.
• Anemia is when you have low numbers of properly functioning red blood cells
in your body.
• In microcytic anemias, body has fewer red blood cells than normal. The red
blood cells it does have are also too small. Several different types of anemias
can be described as microcytic.
• Microcytic anemias are caused by conditions that prevent your body from
producing enough hemoglobin. Hemoglobin is a component of your blood. It
helps transport oxygen to your tissues and gives your red blood cells their red
color.
• Iron deficiency causes most microcytic anemias, body needs iron to produce
hemoglobin. But other conditions can cause microcytic anemias, too. To treat a
microcytic anemia, Physician/ Clinician will first diagnose the underlying cause.
 TYPES OF MICROCYTIC ANAEMIA

• Microcytic anemias can be further described

according to the amount of hemoglobin in the red
blood cells.
Hypochromic microcytic anemias
a. Iron deficiency anemia
b. Thalassemia
c. Sideroblastic anemia
d. Lead Poising
e. Anaemia of chronic disease/ Inflammation
 IRON DEFICIENCY ANAEMIA

• The laboratory features of iron deficiency include a constellation of

findings in the hematology profile.
• Iron deficiency causes red blood cells that are small (microcytic) with
hypochromia, of varying sizes (anisocytosis), and of odd shapes
(poikilocytosis).
• It may possibly cause mild thrombocytosis as well.
• IDA is also associated with reduced ferritin, iron, and % transferrin
saturation levels and increased levels of transferrin and TIBC.
 THALASSEMIA
• These are a heterogeneous group of genetic disorders that
result from a reduced rate of synthesis of α or β chains.
• β‐Thalassaemia is more common in the Mediterranean
region while α‐thalassaemia is more common in the Far
East.
• Clinically the main syndromes are transfusion dependent
thalassaemia major, non‐transfusion dependent
thalassaemia (thalassaemia intermedia) with a
moderate degree of anaemia due to a variety of genetic
defects and thalassaemia minor, usually due to a carrier
state for α‐ or β‐thalassaemia.
• α‐Thalassaemia syndromes
• These are caused by α‐globin gene deletions or less frequently mutations.
• The clinical severity is related to the number of the four α‐globin genes
missing or inactive. Loss of all four genes completely suppresses α‐chain
synthesis and because the a chain is essential in fetal as well as in adult
haemoglobin this is incompatible with life and leads to death in utero
(hydrops fetalis).
• Three α gene deletion leads to a moderately severe (haemoglobin 70–
110 g/L) microcytic, hypochromic anaemia (Fig. 7.7) with splenomegaly.
This is known as Hb H disease because haemoglobin H (β4) can be
detected in red cells of these patients by electrophoresis or in reticulocyte
preparations.
• In fetal life, Hb Barts (γ4) occurs.
• The α‐thalassaemia traits are caused by loss of one or two genes and are
usually not associated with anaemia. The mean corpuscular volume
(MCV) and mean corpuscular haemoglobin (MCH) are low and the red cell
count is over 5.5 × 1012/L.
• Haemoglobin electrophoresis is normal and DNA analysis is needed to be
certain of the diagnosis.
• β‐Thalassaemia syndromes
• β‐Thalassaemia major
• This condition occurs on average in one in four offspring if both parents
are carriers of the β‐thalassaemia trait.
• Either no β chain (β0) or small amounts (β+) are synthesized. Excess α
chains precipitate in erythroblasts and in mature red cells causing
severe ineffective erythropoiesis and haemolysis that are typical of this
disease.
• The greater the α‐chain excess, the more severe the anaemia.
• Over 400 different genetic defects have been detected.
• Unlike α‐thalassaemia, the majority of genetic lesions are point
mutations rather than gene deletions.
• These mutations may be within the gene complex itself or in promoter
or enhancer regions.
• Certain mutations are particularly frequent in some communities and
this may simplify antenatal diagnosis aimed at detecting the mutations
in fetal DNA.
 Laboratory diagnosis of Thalassemia

• 1 There is a severe hypochromic, microcytic anaemia with

normoblasts, target cells and basophilic stippling in the
blood film.
• 2 High performance liquid chromatography (HPLC) is now
usually used as the first‐line method to diagnose haemoglobin
disorders.
HPLC or haemoglobin electrophoresis reveals absence or almost
complete
• Absence of Hb A, with almost all the circulating haemoglobin being Hb
F.
• The Hb A2 percentage is normal, low or slightly raised.
• DNA analysis is used to identify the defect on each allele important in
antenatal diagnosis.
 SIDEROBLASTIC ANAEMIA
• Sideroblastic anemia is a type of anemia that results from abnormal utilization
of iron during erythropoiesis.
• Sideroblastic anemia is a result of abnormal erythropoiesis during heme
production.
• 85% of heme is produced in the cytoplasm and mitochondria of the erythroblast
cells while the remaining is produced in hepatocytes
• There are different forms of sideroblastic anemia, and all forms are defined by
the presence of ring sideroblasts in the bone marrow.
• Ring sideroblasts are erythroid precursors containing deposits of non-heme iron
in mitochondria forming a ring-like distribution around the nucleus.
• The iron-formed ring covers at least one-third of the nucleus rim.
• Sideroblastic anemia is known to cause microcytic and macrocytic
anemia depending on what type of mutation led to it.
• Unlike iron deficiency anemia, where there is depletion of iron stores, patients
with sideroblastic anemia have normal to high iron levels.
• There are two forms of sideroblastic anemia-hereditary and acquired.
 ANAEMIA OF CHRONIC DISEASE
• Anemia of inflammation, also called anemia of chronic
disease or ACD, is a type of anemia that affects people
who have conditions that cause inflammation such as
infections, autoimmune diseases, cancer and chronic
kidney disease.
• In anemia of inflammation, you may have a normal or
sometimes increased amount of iron stored in your
body tissues, but a low level of iron in your blood.
• Inflammation may prevent your body from using stored
iron to make enough healthy red blood cells, leading to
anemia.
Anemia of Chronic Disease and Kidney Failure
 Anaemia of Lead Poisining
• Lead poisoning is the potential impairment caused by lead
ingestion, and it affects almost every organ in the body.
• Lead poisoning usually has no overt symptoms.
• The developing central nervous system of the young child is
particularly likely to be affected.
• Common manifestations are an irreversible reduction in
neurocognitive potential, decreased attention span, and increased
aggressiveness.
• These effects may occur at blood lead levels currently designated
as being below the lead level of concern (10 μg/dL).
• Very high blood lead levels (≥70 μg/dL) are rare and can result in
encephalopathy, coma, and death.
 Case
• The laboratory performed a routine CBC on a 40-year-old female who was
schedule to have elective surgery.
• The following test values were obtained:

• Test Result Reference Range

• Hemoglobin (g/dL) 10 11.7–15.5
• Hematocrit (%) 29.9 35–45
• MCV (fL) 75 80–100
• MCHC (g/dL) 30 32–34
• WBC ( 109/L) 6.0 4.0–11.0
• Platelet count ( 109/L) 200 150–400.
• Serum iron (g/dL) 20 50–170
• Serum ferritin (g/L) 5 20–200
• TIBC (g/dL) 550 250–400
• The morphology showed a few pencil forms and occasional target cells.