Microcytic Anemia, Iron Deff Dan Thalasemia

MICROCYTIC ANEMIA
Thomas G. DeLoughery, M.D.

N Engl J Med 2014;371:1324-31.
DOI: 10.1056/NEJMra1215361
Dr Budi Enoch SpPD

Production red
Mycrocitic cell smaller than
Characterized
anemia normal
Small size of Decreased

these cell production of
hemoglobin
lack of globin product (thalassemia)
The causes of
microcytic anemia a lack of iron delivery to the heme group (iron-
deficiency anemia)
restricted iron delivery to the heme group of

hemoglobin (anemia of inflammation),
defects in the synthesis of the heme group

(sideroblastic anemias).
Thomas G. DeLoughery, M.D.

N Engl J Med 2014;371:1324-31.
DOI: 10.1056/NEJMra1215361
Struktur Hemoglobin Normal
O
O
Fe
Porphyrin ring O2 binding site
Atom oksigen dan atom Fe
berikatan melalui cincin porphyrin
STRUKTUR HEMOGLOBIN
Normokrom normositer Hipokrom mikrositer
THALASSEMIA
Thalassemias are diseases of hemoglobin synthesis
α-thalassemia
chromosome 16
β-Thalassemia
chromosome 11
α-thalassemia  Africa, the Mediterranean area, and
Southeast Asia,
hemoglobin H disease and hemoglobin Bart’s 
Mediterranean area and Southeast Asia.
Africa is trans
cis form is found in other areas
β-Thalassemia  Mediterranean area and Southeast
Asia.
 heterozygous (thalassemia minor)
 residual β-chain synthesis, resulting in an intermediate
phenotype (thalassemia intermedia)
 homozygous (thalassemia major)
thalassemia minor  mild microcytic anemia.
thalassemia intermedia  transfusion-dependent

anemia to anemia that is slightly more severe than
thlassemia minor.
thalassemia major  manifested soon after birth

as severe transfusion-dependent anemia.
Hemoglobin E disease  Southeast Asia
lysine is substituted for glutamine at position 26 of the
β chain.
Heterozygous  microcytosis with target cell
Homozygous  mild anemia
β-Thalassemia & Hemoglobin E  severe
phenotype, transfusion-dependent anemia
Sel target
ANEMIA OF INFLAMMATION
Etiology renal production of erythropoietin is
suppressed by inflammatory cytokines,
resulting in decreased red-cell production.
lack of iron availability for developing red

cells can lead to microcytosis
Reduced iron absorption
lack of iron  protein
hepcidin (acute phase
reactant) Reduced release of iron
from body stores.
Mechanism???
denotes divalent metal transporter 1 (DMT1)
IRON DEFICIENCY
>> most common anemia.
Women loss iron >> than men  menses  1 -3

mg/day (iron loss) + dietary intake inadequate.
Pregnancy women  need 6 mg per day.
Athletes  Gastrointestinal tract blood is the source
of iron loss, and exercise-induced hemolysis leads to
urinary iron losses; protein hepcidin
Cont......
Obesity & its surgical treatment (Bariatric surgery)
 Protein hepcidin
 Bariatric surgery, 50% iron deficiency. The main site of
iron absorption is the duodenum, surgery that involve
bypassing this part of the bowel are associated with an
increased incidence of iron deficiency.
DIAGNOSIS
Blood smear (microscopic)
Microcytosis cell; hypochromia (increase in the size of
the central pallor of red cell).
NORMAL
Central pallor is
less than one
third of the cell
diameter
shows β-thalassemia and hemoglobin E disease, characterized
by target cells (thick arrows), red cells that are smaller than a
lymphocyte nucleus (thin arrows), and occasional nucleated
red cells (arrowheads).
shows severe iron deficiency, with hypochromia (thin
arrows), microcytosis (thick arrows), and a pencil cell
(arrowhead).
Cont... β-thalassemia minor
Patients with β-thalassemia minor present with a
hemoglobin level of 10 to 13 g per deciliter and a mean
corpuscular volume of 65 to 75 fl.
These patients have an increased production of
hemoglobin that contains the δ chain (hemoglobin
A2), so electrophoresis typically shows an increased
hemoglobin A2 fraction.
Cont.... α-Thalassemia trait
α-Thalassemia trait is electrophoretically silent. The
diagnosis can be made by exclusion in a patient who
presents with microcytosis but only mild or no anemia
and who is iron-replete. A precise diagnosis requires
DNA analysis.
Cont... Diagnosis Hemoglobin H disease
The presence of hemoglobin H (a tetramer of β
chains) on electrophoresis, along with severe
microcytosis, is diagnostic of hemoglobin H disease.
Hemolysis may also be evident and splenomegaly is
observed on physical examination in patients with
hemoglobin H disease.
Cont... anemia of inflammation
An erythropoietin value that is not appropriately
increased in patients with anemia and preserved renal
function
The presence of adequate iron stores
no other cause for the anemia.
Microcytic Retikulosit Serum Serum levels
anemia hemoglobin iron level of
transferrin
Thalassemia Low High -
Iron Low Low elevated
deficiency
Anemia of normal Low -
inflamation
Serum ferritin for iron deficiency:

 Ferritin level of 15 ng/mL  iron deficiency
 Ferritin level 40 ng/mL  iron deficiency, absence
inflamation
 Ferritin level 70 ng/mL  iron deficiency, presence
inflamation
THERAPY - Thalassemia
Thalassemia severe : chronic transfusions will lead
to normal growth and development. However,
without aggressive iron chelation, endocrine failure
will ensue, and most will die in the second or third
decade of life from iron overload. Stem-cell
transplantation, if available, is the best treatment
option: in young patients, there will be fewer
complications than with other treatments, and if
transplantation is successful, there is no need for
lifelong therapy with transfusion and chelation.
THERAPY - Thalassemia
Thalassemia intermedia & Hemoglobin H : disease is more
challenging because of the variety of presentations. For
patients who are transfusion-dependent, iron chelation is
essential. These patients have increased iron absorption, so
iron overload can occur even in those with minimal transfusion
requirements.
Thalassemia trait : require no specific therapy. However, if they

are considering childbearing, the partner should be screened
for thalassemia by checking the mean corpuscular volume; if it
is less than 75 fl, more specific genetic testing is necessary.
ANEMIA OF INFLAMMATION
Eliminate the underlying cause, but in many patients
that cannot be done
Because of the low erythropoietin levels,
erythropoiesisstimulating agents have been used
successfully in patients with anemia of inflammation to
increase the red-cell count, but the use of these agents
is limited owing to their cost and safety concerns.
In animal models of anemia, blocking hepcidin
reduces anemia, and this strategy holds much promise
for the future.
Therapy iron deficiency
1. Oral Iron Therapy
Traditionally, ferrous sulfate (325 mg [65 mg of
elemental iron] orally three times a day) has been
prescribed for the treatment of iron deficiency.
 increase iron absorption  meat protein ; vit.C 500 unit.
 decrease iron absorption  Calcium + Fiber ; tea ;coffee.
The reticulocyte count should rise in 1 week, and the

hemoglobin level starts rising by the second week of
therapy. Iron therapy should be continued until iron
stores are replete.
Cont...
Condition, no response to oral iron:
 Stomach pain + constipation
 Bleeding (inflammatory bowel disease)
 Celiac disease or bowel surgery
2. Parenterally administered Iron

 no response to oral iron therapy
 Without side effect of GI & absorption
 Disadvantage  infusion reaction
Cont...
THE FUTURE
As a genetic disease, thalassemia remains an ideal target
for gene therapy.
Manipulation of the hepcidin pathway holds great promise
for treating anemia of inflammation.
Although tremendous progress has been made, much
remains to be elucidated about iron metabolism, including
the receptor for absorption of heme iron. Finally, the role
of new markers — such as polymorphisms in a key iron-
sensing protein, transmembrane protease serine 6
(TMPRSS6), which may increase the risk of iron deficiency
— remains to be explored

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MICROCYTIC ANEMIA

Thomas G. DeLoughery, M.D.

Dr Budi Enoch SpPD

Small size of Decreased

restricted iron delivery to the heme group of

defects in the synthesis of the heme group

Thomas G. DeLoughery, M.D.

thalassemia intermedia  transfusion-dependent

thalassemia major  manifested soon after birth

lack of iron availability for developing red

Women loss iron >> than men  menses  1 -3

Serum ferritin for iron deficiency:

Thalassemia trait : require no specific therapy. However, if they

The reticulocyte count should rise in 1 week, and the

2. Parenterally administered Iron

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