Microcytic Hypochromic Anemia & Thalassemia
Microcytic Hypochromic Anemia & Thalassemia
Microcytic Hypochromic Anemia & Thalassemia
Presentation On
Microcytic Hypochromic
Anemias & Thalassemias.
Dr Dipalok Mukherjee
Resident, Phase A.
Points To Ponder
The Red Cells Iron Deficiency Anemia
Hemoglobin Nutritional & Metabolic
The hemoglobin- Aspects of Iron
Dissociation Curve Anemia of Chronic Disorders
Role of Erythropoietin
Sideroblastic Anemias
Normal Values & Hematinics
Genetic Disorders of
Red Cell Indices Hemoglobin Synthesis
Anemias: General
The Thalassemias
Consideration
Microcytic Hypochromic Diagnostic Algorithm
Anemias
© Dr Dipalok Mukherjee
The Red Cells
Red cells are the most numerous of all blood cells
Specialized for and C carriage
They have a 4-month (120 days) lifespan
Mature cells lack nuclei, and other cytoplasmic structures;
hence, cannot undergo mitosis.
Biconcave discs with a diameter of 7-8µm in large blood
vessels with an average diameter of 7.2µm
Shape changes to parachute-like conformation in
capillaries.
© Dr Dipalok Mukherjee
The Red Cells Photomicrograph
Fig: (A) Mature red cells in a peripheral blood film, (B) Scanning electron
micrograph of red cells (x2500).
© Dr Dipalok Mukherjee
Red Cell Metabolism
The Embden–Meyerhof
pathway
Glucose enters the red cell
from plasma by facilitated
transfer.
Metabolized to lactate.
Each molecule of glucose
produces two molecules of
ATP and thus two high-
energy phosphate bonds
are generated.
Also generates NADH
which is required by
methemoglobin reductase
to reduce functionally dead
methemoglobin containing
Fig: The Embden–Meyerhof glycolytic pathway. ferric iron.
The Luebering–Rapoport shunt regulates the
concentration of 2,3-DPG in the red cell.
© Dr Dipalok Mukherjee
Red Cell Membrane
The membrane skeleton is formed by structural proteins that include α and β spectrin,
ankyrin, protein 4.1, and actin. These proteins form a horizontal lattice on the internal
side of the red cell membrane and are important in maintaining the biconcave shape.
© Dr Dipalok Mukherjee
Hemoglobin
Hemoglobin is a specialized protein
for O and CO carriage.
Each molecule of normal adult
hemoglobin A (Hb A) consists of four
polypeptide chains, 𝛂𝟐 𝛃𝟐 , each with
its own heme group.
Heme synthesis occurs largely in the
mitochondria.
The structure of heme contains a 𝐅𝐞𝟐
ion at its center, each connected to
globin chains in a pocket, forming a
Fig: The structure of heme.
hemoglobin molecule.
© Dr Dipalok Mukherjee
Hemoglobin Synthesis
Hemoglobin synthesis in the
developing red cell
© Dr Dipalok Mukherjee
The Hemoglobin Dissociation
Curve
© Dr Dipalok Mukherjee
Erythropoietin Production
Erythropoietin stimulates
erythropoiesis and so
increases delivery.
Hypoxia induces hypoxia
inducible factors (HIFs) α
and β, which stimulate
erythropoietin production.
Von-Hippel–Lindau (VHL)
protein breaks down HIFs.
Mutations in VHL, PHD2 or
HIF-1α underlie congenital
polycythemeia.
© Dr Dipalok Mukherjee
Normal Values for
Blood Cells & Hematinics
Reticulocyte count (x10 /L) (per cent)
Adults and children 50-100 (0.5-2.5%)
Full term/cord blood 120-400 (2-6%)
© Dr Dipalok Mukherjee
Red Cell Indices:
MCV & MCH
Mean corpuscular volume (MCV) is derived from packed cell volume (PCV) and total
number of red cells in that particular volume.
Expressed in femtoliter (fL).
It helps in morphological classification of anemias.
MCV= PCV/number of red cells.
Adult 80-95
At birth 106
At one year 70-80
10-12 years 77-91
Mean corpuscular hemoglobin (MCH) describes mean amount of Hb per red blood
cells and expressed in picograms (pg). A
Subnormal MCH occurs in microcytosis with or without low Hb concentration as
in thalassemia minor or iron deficiency.
MCH= Hb conc. (gm/L)/number of RBC/L
Adult MCH: 27-34pg.
© Dr Dipalok Mukherjee
Red Cell Indices:
MCHC & RDW
Mean corpuscular hemoglobin concentration (MCHC) is the measure of Hb concentration
(gm/dL) in a volume of red cells (PCV) and expressed in gm/dL.
Red cell distribution width (RDW) provides an assessment of variation in cell volume
which corresponds to the microscopic analysis of the degree of anisocytosis.
© Dr Dipalok Mukherjee
Anemias: General Consideration
Anemia is defined as a reduction in the hemoglobin concentration of the
blood below normal for age and sex.
Global incidence
The World Health Organization (WHO) defines anemia in adults as a
hemoglobin less than 130g/L in males and 120g/L in females.
On this basis, anemia was estimated in 2010 to occur in about 33% of
the global population.
Prevalence was greater in females than males at all ages most
frequent in children less than 5 years old.
Anemia was most frequent in South Asia; and Central, West and East
Sub-Saharan Africa.
The main causes are iron deficiency (life-long poor diet combined
with menstruation, repeated pregnancies, hookworm,
schistosomiasis), the anemia of chronic disorders, sickle cell
diseases, thalassemia, and malaria.
© Dr Dipalok Mukherjee
Classification of Anemias
Anemias can be classified as:
Morphologically depending on the red cells indices.
Etiological classification.
Morphological classification Etiological classification
Microcytic, hypochromic Blood loss (hemorrhagic)
© Dr Dipalok Mukherjee
Morphological
Classification of Anemias
The most useful classification is that based on red cell indices.
Suggests nature of the primary defect.
May also indicate an underlying abnormality before overt anemia has
developed.
Microcytic, hypochromic Normocytic, Macrocytic
normochromic
MCV <80fL MCV 80-95fL MCV >95fL
MCH <27pg MCH ≥27pg Megaloblastic: vitamin 𝐁𝟏𝟐
or folate deficiency.
Iron deficiency anemia, Many hemolytic anemias, Non-megaloblastic:
thalassemia, anemia of anemia of chronic diseases alcohol, liver disease,
chronic diseases (some (some cases), after acute myelodysplasia, aplastic
cases), sideroblastic anemia. hemorrhage. anemia.
Lead poisoning. Mixed deficiencies
Bone marrow failure (eg.
post chemotherapy,
infiltration by carcinoma).
© Dr Dipalok Mukherjee
Basic Pathophysiological
Categories of Anemias
Blood loss
Impaired red cell production
a) Inadequate supply of nutrients essential for erythropoiesis: iron
deficiency, vitamin 𝟏𝟐 or folate deficiency, combined deficiency, protein-energy
malnutrition, vitamin C and other less common deficiencies.
b) Depression of erythropoietic activity
c) Anemia associated with chronic disorders such as infection, connective
tissue disorders, disseminated malignancies, inflammatory disorders.
d) Anemia associated with renal failure
e) Aplastic anemia
f) Anemia due to replacement of normal bone marrow by: leukemia,
lymphoma, myeloproliferative disorders, myeloma, myelodysplastic disorder.
g) Anemia due to inherited disorders such as thalassemia.
Excessive red cell destruction
a) Due to intrinsic defects in red cells (intra corpuscular defects)
b) Due to extrinsic effects on red cells (extra corpuscular defects).
© Dr Dipalok Mukherjee
Clinical Features of Anemias
The major adaptations to anemia occur in the
cardiovascular system with increased stroke volume and tachycardia
the hemoglobin dissociation curve.
The presence or absence of clinical features can be considered under
four major headings.
a) Speed of onset
b) Severity
c) Age
d) The hemoglobin dissociation curve.
© Dr Dipalok Mukherjee
Anemias: Clinical Manifestations
Symptoms
Common Fatigue, tiredness, effort intolerance, effort dyspnea,
palpitations.
Less common Faintness, giddiness, pounding in the ears, effort angina*.
Signs
General
Common Pallor
Less common High cardiac output state, congestive cardiac failure*.
Specific
Koilonychia Iron deficiency anemia
Jaundice hemolytic, megaloblastic anemias,
Leg ulcers Sickle cell anemia
Bone deformities Thalassemia major.
© Dr Dipalok Mukherjee
Anemias: Physical Signs
Fig: Pallor of the conjunctival mucosa (a) and of the nail bed (b) in two patients
with severe anemia (hemoglobin 60g/L), (c) Retinal hemorrhages in a patient
with severe anemia (hemoglobin 25g/L) caused by severe hemorrhage.
© Dr Dipalok Mukherjee
Microcytic Hypochromic Anemias
(Pathophysiological Classification)
Disorders of Iron metabolism
Iron deficiency anemia
Anemia of chronic disorders
Atransferrinemia
Familial microcytic hypochromic anemias
Disorders of globin synthesis
Thalassemia
Hb-E Trait and Hb-E disease
Hb - C disease
Disorders of porphyrin and heme synthesis
Defective δ-aminolevulinic acid (ALA) synthesis
Vit B12 deficiency
Defective ALA synthetase activity
Defective vit 𝟏𝟐 metabolism
Deficiency of heme synthesis
Lead intoxication.
© Dr Dipalok Mukherjee
Microcytic Hypochromic Anemias:
Differentials
The thalassemias
Anemia of chronic
disorders
Fig: The causes of a hypochromic microcytic anemia.
Sideroblastic anemias. These include iron deficiency or of iron release from
macrophages to serum (anemia of chronic
inflammation or malignancy), failure of
protoporphyrin synthesis (sideroblastic anemia) or
of globin synthesis (α- or β-thalassemia). Lead also
inhibits heme and globin synthesis.
© Dr Dipalok Mukherjee
Iron Deficiency Anemia (IDA)
Iron is one of the most common elements in the Earth’s crust.
Yet iron deficiency is the most common cause of anemia, affecting about 500
million people worldwide.
© Dr Dipalok Mukherjee
Dietary Iron
Iron is present in food as ferric
hydroxides and ferric–protein and
heme–protein complexes.
Both the iron content and the
proportion of iron absorbed differ
from food to food.
In general meat, in particular liver,
is a better source than vegetables,
eggs or dairy foods.
The average diet contains 10–15
mg iron daily, from which only 5–
10% is normally absorbed. The
proportion can be increased to 20–
30% in iron deficiency or
pregnancy.
Even in these situations most
dietary iron remains unabsorbed.
© Dr Dipalok Mukherjee
Nutritional & Metabolic Aspects of
Iron
Table: Distribution of body iron.
Total body iron content of the normal adult varies from 3-5gm depending on
age, sex, and weight of the individual. It is greater in male than female.
© Dr Dipalok Mukherjee
Regulation of Iron Absorption
© Dr Dipalok Mukherjee
Factors Affecting Iron Absorption
The following table enumerates factors affecting luminal
iron absorption.
© Dr Dipalok Mukherjee
Cellular Uptake of Iron
Transferrin
+
Iron (𝐅𝐞𝟑 ) Fig: Mechanisms
involved in tissue iron
uptake.
Transferrin-Iron-
Transferrin receptor
1 (TfR1) complex on
cell surface
© Dr Dipalok Mukherjee
Daily Iron Cycle
Fig: Daily iron cycle. Most of the iron in the body is contained in circulating
hemoglobin and is reutilized for hemoglobin synthesis after the red cells die. Iron is
transferred from macrophages to plasma transferrin and so to bone marrow
erythroblasts. Iron absorption is normally just sufficient to make up for iron loss.
© Dr Dipalok Mukherjee
Hepcidin: The Iron Homeostasis
Regulator
Hepcidin is a polypeptide produced by liver cells.
© Dr Dipalok Mukherjee
Factors Affecting Hepcidin Synthesis
Factors favoring synthesis Factors reducing synthesis
Erythropoietin
© Dr Dipalok Mukherjee
Iron Excretion & Requirements
Iron is lost through the following:
Desquamated epithelial cells from the gastrointestinal tract in stool
Excretion in the urine and sweat
Loss of hair and nails.
© Dr Dipalok Mukherjee
Iron Deficiency Anemia: Causes
Chronic blood loss Increased demands
a) Uterine Prematurity
b) Gastrointestinal Growth
Chronic upper GI bleeding: bleeding Pregnancy
peptic ulcer, esophageal varices,
aspirin (or other non-steroidal anti- Erythropoietin therapy
inflammatory drugs) ingestion. Malabsorption
Malignancies: Carcinoma of the Gluten-induced enteropathy,
stomach, caecum, colon or rectum.
Gastrectomy
Parasites: hookworm, schistosomiasis.
Autoimmune gastritis
Chronic inflammatory conditions:
angiodysplasia, inflammatory bowel Poor diet
disease, piles, diverticulosis. A major factor in many developing
c) Rarely: hematuria, hemoglobinuria, countries.
pulmonary hemosiderosis, self-inflicted
blood loss.
© Dr Dipalok Mukherjee
Clinical Features
When iron deficiency is developing, the reticuloendothelial stores (hemosiderin and
ferritin) become completely depleted before anemia occurs.
As the condition develops, the patient may show the general symptoms
and signs of anemia.
While in children it can cause irritability, poor cognitive function, and a decline in
psychomotor development.
© Dr Dipalok Mukherjee
Physical Findings
Fig: Iron deficiency anemia. (a) Koilonychia: typical ‘spoon’ nails. (b)
Angular cheilosis: fissuring and ulceration of the corner of the mouth.
© Dr Dipalok Mukherjee
Iron Deficiency Anemia: Diagnosis
© Dr Dipalok Mukherjee
Laboratory Findings
Investigations Findings
TIBC Raised
Hb electrophoresis Normal.
© Dr Dipalok Mukherjee
Peripheral Blood Film: IDA
Fig: The peripheral blood film in severe iron deficiency anemia. The cells are
microcytic and hypochromic (blue arrowhead) with good number of pencil-
shaped poikilocytes (red arrowhead).
© Dr Dipalok Mukherjee
Investigation of the Cause of
Iron Deficiency
Cause Investigations
Menorrhagia Test for coagulation eg. PT, aPTT; test for von-
Willebrand disease.
Gastrointestinal blood loss Occult blood test
Stool routine microscopy for ova
Urea breath test for Helicobacter infection
Appropriate upper and lower GI endoscopy, and/or
radiology.
Autoimmune gastritis Parietal cell antibodies, serum gastrin levels
Gluten induced enteropathy Transglutaminase antibodies, duodenal biopsy
Celiac axis angiogram Angiodysplasia
Hematuria Urinary routine microscopy
Chest x-rays Pulmonary hemosiderosis.
© Dr Dipalok Mukherjee
Iron Deficiency Anemia: Treatment
The underlying cause is treated as far as Table: Failure of response to oral iron.
possible.
Iron is given to correct the anemia and
replenish iron stores.
Oral iron therapy should be given for long
enough both to correct the anemia and to
replenish body iron stores, which usually
means for at least 6 months.
Best oral preparation is ferrous sulphate.
Other preparations maybe ferrous
fumerate, ferrous gluconate.
The hematological response to parenteral
iron is no faster than to adequate dosage
of oral iron, but the stores are
replenished faster.
Parenteral iron should not be given in 1st
trimester of pregnancy.
© Dr Dipalok Mukherjee
Anemia of Chronic Disorders (ACDs)
One of the most common anemias; associated with many chronic inflammatory
and malignant diseases.
With iron deficiency it accounts for about two-thirds of the world’s anemias.
© Dr Dipalok Mukherjee
Pathogenesis of ACDs
Chronic Fig: Flow chart
inflammation, depicting the
malignancy pathogenesis of
anemia of chronic
disorders.
↑ Cytokines eg.
IL6, IL1 ↑ Cytokines eg. IL6,
IL1, TNF, direct
inhibition by IFN-γ
↑ Hepcidin
↓ Erythropoietin
↓ Release of 𝐅𝐞𝟑
from
macrophages. ANEMIA (ACDs)
© Dr Dipalok Mukherjee
Peripheral Blood Film: ACDs
Fig: Despite a reduction in the total number of red cells, the RBC indices are
normal, and the cells have the typical area of central pallor without
widespread variation in size and shape (American Society of Hematology).
© Dr Dipalok Mukherjee
Sideroblastic Anemias
This is a refractory anemia defined by the presence of many pathological ring
sideroblasts in the bone marrow.
These are abnormal erythroblasts containing numerous iron granules
arranged in a ring or collar around the nucleus.
There is also usually erythroid hyperplasia with ineffective erythropoiesis.
Sideroblastic anemia is diagnosed when ≥15% of marrow erythroblasts are
ring sideroblasts.
They can be found at lower numbers in a variety of other hematological
conditions.
Sideroblastic anemia is classified into different types and the common link is a
defect in heme synthesis.
© Dr Dipalok Mukherjee
Classifications of
Sideroblastic Anemias
Hereditary
X chromosome-linked ALA-S* mutation
Rarely with spinocerebellar degeneration and ataxia (usually occurs in males,
transmitted by females; also occurs rarely in females).
Other rare autosomal types involving mitochondrial proteins or thiamine
phosphorylation.
Acquired
Primary
Myelodysplasia (refractory anemia with ring sideroblasts)
Secondary (reversible)
a) Drugs, e.g. anti-tuberculous eg. Isoniazid; alcohol, lead poisoning.
b) Other benign conditions e.g. hemolytic anemia, megaloblastic anemia,
rheumatoid arthritis.
© Dr Dipalok Mukherjee
Siderocytes & Sideroblasts
Siderocytes
Red cells containing granules of non-heme iron which give a positive Prussian
blue reaction. Siderocytes are not normally found in red cells in the peripheral
blood, but small numbers are seen following splenectomy.
Sideroblasts
Sideroblasts are erythroblasts with Prussian blue positive iron granules in their
cytoplasm.
Three types of sideroblasts are defined on the basis of the number, size, and
distribution of the siderotic granules:
The first type is seen in normal bone marrow.
The second type is abnormal and may be found in conditions with
dyserythropoiesis or hemolysis.
The third type found where synthesis is disturbed, e.g. the primary and
secondary sideroblastic anemias.
© Dr Dipalok Mukherjee
Laboratory Findings
Investigations Findings
© Dr Dipalok Mukherjee
PBF & Bone Marrow in
Sideroblastic Anemias
Fig: Pappenheimer bodies in peripheral blood Fig: Ring sideroblasts with a perinuclear ring
following splenectomy. of iron granules in sideroblastic anemia.
© Dr Dipalok Mukherjee
Genetic Disorders of Hemoglobin
Synthesis
Genetic disorders of hemoglobins may be classified into two broad groups:
The hemoglobinopathies are defective Hb due to abnormal globin moiety
formation.
The common abnormal hemoglobins are
Hemoglobin Structural formula
Hb-S α β
→
Hb-C α β
→
Hb-E α β
→
Hb-D Punjab α β
→
© Dr Dipalok Mukherjee
Geographical Distribution
© Dr Dipalok Mukherjee
Normal Hemoglobins In Humans
Hb is a conjugated protein of molecular weight of 64,000 consisting of two polypeptide
chains.
Each polypeptide chains is attached to a heme moiety.
Human Hb exists in a number of types depending on the globin moiety.
The heme, however, is identical in all types.
Hb A 𝛂 𝟐 𝛅𝟐 1.5-3.2
Gower-2 𝛂𝟐 𝛆𝟐 ---
Portland 𝛇𝟐 𝛌𝟐 ---
© Dr Dipalok Mukherjee
Molecular Aspects of
Hemoglobin Synthesis
Fig: The globin gene clusters on
chromosomes 16p and 11q. In
embryonic, fetal and adult life,
different genes are activated or
suppressed. The different globin
chains are synthesized
independently and then combine
with each other to produce the
different hemoglobins.
(b) Synthesis of individual globin
chains in prenatal and postnatal
life.
© Dr Dipalok Mukherjee
The Thalassemias
The thalassemias are a heterogeneous group of genetic disorders that result
from a reduced rate of synthesis of α- or β-globin chains.
© Dr Dipalok Mukherjee
β-Thalassemias
The genetic mutations of β-thalassemias leads to a decrease rate of β chain synthesis.
Ultimately, causes a reduction in normal Hb A amount in red cells.
Two main types are recognized.
𝛃 thalassemia is characterized by incomplete suppression
𝛃𝟎 thalassemia by complete absence of chain synthesis.
Table: The β-thalassemias and related syndromes: electrophoretic phenotypes
Hemoglobin (%)
Disorders
A 𝐀𝟐 F
β-thalassemia minor 90-95 3.5-7.0 1-5
δβ-thalassemia minor 80-95 1.0-3.5 5-20
β-thalassemia major
β-thal+ 10-90 1.5-4.0 10-90
β-thal0 0 1.0-2.0 98
HPFH* 60-85 1.0-2.0 15-35
© Dr Dipalok Mukherjee
α-:β-Globin Chain Synthesis Ratio
© Dr Dipalok Mukherjee
Thalassemias: Clinical Features
Severe anemia becomes Infections occur frequently.
apparent at 3–6 months after
a) Due to iron overload: Klebsiella
birth.
or Yersinia, and fungal infection.
Failure to thrive, pallor, and a b) Following splenectomy:
swollen abdomen within the first Pneumococcal, Haemophilus,
year. and meningococcal infections.
Enlargement of the liver and Hepatitis
spleen. Transfusional hepatitis B, C, and HIV
Expansion of bones caused by infections; and hemosiderosis.
intense marrow hyperplasia leads Hepatocellular carcinoma from
to a thalassemic facies. hepatic fibrosis/cirrhosis
a) Due to iron overload
Thalassemia major is the disease
that most frequently underlies b) Due to chronic hepatitis B or C.
transfusional siderosis. Osteoporosis
Endocrinopathies
Congestive cardiac failure from Cardiomyopathy and
plasma overload.
arrhythmias.
© Dr Dipalok Mukherjee
Hydrops Fetalis
Fig: α-Thalassemia: hydrops fetalis, the result of the deletion of all four α-globin
genes (homozygous 𝛂𝟎 thalassemia). The main hemoglobin present is Hb Barts
( 𝛌𝟒 ). The condition is incompatible with life beyond the fetal stage.
© Dr Dipalok Mukherjee
Clinical Features
Fig: Thalassemic facies The skull is Fig: Skull X-ray in β-thalassemia major without
bossed with prominent frontal and chronic transfusion support. There is a ‘hair-on-
parietal bones; the maxilla is also end’ appearance as a result of expansion of the
enlarged. Results from chronic anemia bone marrow into cortical bone.
and compensatory hyperplasia of the
marrow. This can be prevented by
transfusion.
© Dr Dipalok Mukherjee
Thalassemias:
Laboratory Diagnosis
Investigations Findings
MCV/MCH Reduced, very low for the degree of anemia.
Peripheral blood film Marked hypochromic, microcytic cells
with significant poikilocytosis, target cells, and fragmented
cells (hemolysis), polychromatic cells; nucleated red cells
are also seen in post-splenectomy state; basophilic
stippling.
Reticulocyte count Usually increased; >5%
Serum iron Normal
TIBC Normal
Serum ferritin Normal
Bone marrow iron stores Present
Bone marrow morphology Hyperplastic, micronormoblastic; in relation to the degree of
anemia.
Erythroblast iron Present
Hb electrophoresis Hb A raised in β forms.
© Dr Dipalok Mukherjee
α-Thalassemias:
Peripheral Blood Films
Fig: (a) α-Thalassemia: Hb H disease. The blood film shows marked hypochromic, microcytic
cells with target cells, and poikilocytosis. (b) α-Thalassemia: Hb H disease. Supravital
staining with brilliant cresyl blue or methylene blue reveals multiple fine, deeply stained
deposits (‘golf ball’ cells) caused by precipitation of aggregates of β-globin chains.
© Dr Dipalok Mukherjee
β-Thalassemias:
Peripheral Blood Films
Fig: β-Thalassemia major: Peripheral blood Fig: β-Thalassemia major: Peripheral blood film
film showing prominent hypochromic after splenectomy in which hypochromic cells,
microcytic cells, target cells, and an target cells, and erythroblasts are prominent.
erythroblast. Some normochromic cells are Pappenheimer and Howell–Jolly bodies are
present from a previous blood transfusion. also seen, and the platelet count is raised.
© Dr Dipalok Mukherjee
HPLC &
Hemoglobin Electrophoresis
Fig: (a) High-performance
liquid chromatography (HPLC).
The different hemoglobins elute
at different times from the
column and their
concentrations are read
automatically. In this example,
the patient is a carrier of sickle
cell disease. (b) Hemoglobin
electrophoretic patterns in
normal adult human blood and
in subjects with sickle cell (Hb S)
trait or disease, β-thalassaemia
trait, β-thalassaemia major, Hb
S/β-thalassemia or Hb S/Hb C
disease and Hb H disease.
© Dr Dipalok Mukherjee
Thalassemias:
Treatment Modalities
Regular blood transfusions is required usually 2-3 units every 3-4 weeks.
Iron chelation is essential. The available drugs are deferiprone,
deferoxamine, and deferasirox that have improved quality of life.
Regular folic acid supplementation should be provided.
Where possible, splenectomy should be deferred until over 6 years of age.
Lifelong oral penicillin is required.
Endocrine therapy.
Immunization against hepatitis B, C, and before splenectomy.
Allogeneic stem cell transplantation offers the prospect of permanent
cure.
Trials of gene therapy for treating the thalassemia major phenotype are in
progress.
© Dr Dipalok Mukherjee
β-Thalassaemia Trait (Minor)
This is a common, usually symptomless abnormality characterized like
α-thalassemia trait by
a hypochromic, microcytic blood picture
MCV and MCH low but high red cell count (>5.5 × 1012/L) and
mild anemia (hemoglobin 100–120 g/L)
usually more severe than α-thalassemia trait
a raised level of Hb (>3.5%) confirms the diagnosis.
© Dr Dipalok Mukherjee
Non Transfusion Dependent Thalassemia
(Thalassemia Intermedia): A Clinical
Syndrome
Thalassemia intermedia is a clinical syndrome caused by a variety of
genetic defects requiring intermittent transfusions.
This is thalassemia of moderate severity (hemoglobin 70–100g/L)
without the need for regular transfusions.
Although transfusion may occasionally be required, for example
during an acute illness with temporary suppression of erythropoiesis.
Few examples are
Hb H disease
Hb E/β Thalassemia
β-Thalassemia with coinherited hereditary persistence of fetal
hemoglobin (HPFH)
δβ-thalassaemia
© Dr Dipalok Mukherjee
Special Tests & Upcoming Modalities:
α-Thalassemias
Genetic testing is currently available to establish the diagnosis and clarify the
genetic abnormalities in patients with a family history or laboratory results
suggestive of an α-thalassemia syndrome.
Polymerase chain reaction (PCR) and restriction endonuclease testing may
be used.
Recombinant DNA technology can be diagnostic, but is still considered
research.
Other genetic tests include gene mapping and anti-L globin monoclonal
anti-bodies.
Genetic techniques can be helpful in some cases in which both the patient’s
and the parents’ α-chain configurations are elucidated exactly, which can be
useful in predicting the risk that a couple’s future offspring will be affected.
© Dr Dipalok Mukherjee
Special Tests & Upcoming Modalities:
β-Thalassemias
Prenatal diagnosis is possible through analysis of DNA obtained via chorionic
villi sampling at 8-10 weeks’ fetal gestation or by amniocentesis at 14-20
weeks’ gestation.
In most laboratories, the DNA is amplified using PCR and then is analyzed for
the presence of the thalassemia mutation using a panel of oligonucleotide
probes corresponding to known thalassemia mutations.
Since the genetic defects are quite variable, family genotyping usually must
be completed for diagnostic linkage (segregation) analysis.
With the anticipated availability of large-scale mutation screening by DNA chip
technology, extensive pedigree analyses may be obviated.
Physicians can perform fetal blood sampling for Hb chain synthesis at 18-22
weeks’ gestation, but this procedure is not as reliable as DNA analysis
sampling methods.
Genetic therapy strategies are currently in the early stages of development.
© Dr Dipalok Mukherjee
Laboratory Diagnosis of
Microcytic Hypochromic Anemias: In
Essence
Criteria IDA ACDs Thalassemias Sideroblastic IRIDA*
anemias
MCV/MCH ↓ N or Very ↓ ↓ or ↑ ↓
mild ↓
S. iron ↓ ↓ N ↑ ↓
TIBC ↑ ↓ N N ↓
S. Ferritin ↓ ↑ N ↑ ↑
Consider homozygous
Serum iron studies Thal/ Hb-pathies Hb electrophoresis/HPLC
confirmation
↓ S. Fe, ↑ S. Fe,
↓ S. Fe, ↑TIBC,
normal/↓ TIBC, normal TIBC,
↓ Ferritin
normal/↑Ferritin ↑ Ferritin