Anemia

Definition of anemia: Decrease of hemoglobin

concentration below the normal levels taking in
.consideration age, sex and altitude

(WHO criteria):
Men: Hb<13.0 g/dLor Ht<40%
Women: Hb<12.0 g/dLor Ht<36%

Causes of anemia:
1- Anemias due to blood loss:
Sudden loss Chronic loss
Accidents - Hemorrhoids
Surgery - Ulcers in the
stomach

:Anemias due to deficient erythropoiesis -2

Iron leukemia
deficienc Chronic disease
y Aplastic anemia
Vitamin
B12
deficienc
y
Folic
acid
deficienc
y
3- Anemias due to excessive red blood cell
destruction:
Congenital:
Defect in red blood cell membrane as:
- Hereditary spherocytosis
- Hereditary eleptocytosis
Defect in red blood cell enzymes as:
- G6PD deficiency
 Defect in red blood cell hemoglobin.
- Sickle cell disease
- Thalassemia
Acquired:
Enlarged spleen
Mechanical damage to red blood
cells
Autoimmune disease
Paroxysmal nocturnal hemoglobinuria

Types of anemias according to RBCs (II)

:morphology

Microcytic anemias suggest altered heme or globin

.synthesis (eg, iron [Fe] deficiency,)

Normochromic-normocytic anemias suggest a

hypoproliferative or hypoplastic

Macrocytic anemias (large RBCs), which suggest a

defect in DNA synthesis. These anemias are usually
caused by defective vitamin B12 or folic acid
metabolism or by an interference with DNA synthesis
.by chemotherapeutic cytoreductive drugs

Normal Red Blood Cell Indecies:

Mean corpuscular volume (MCV): 80 - 100 fl
Mean cell hemoglobin (MCH): 26 - 32 pg
Mean cell hemoglobin concentration (MCHC): 32 - 36
g/dL

Evaluation of Microcytic
Anemia

Microcytosis means decreased RBC size below normal level

(less than 80 fL for adults).
The most common causes of microcytic anemia:
Iron deficiency anemia.
Anemia of chronic disease.
 Sideroblastic anemia.
Hereditary spherocytosis
Thalassemia.

Summary of microcytic anemias

Iron deficiency
anemia
Iron source in food
Animal sources (Hem iron): animal and liver
Fruit sources and vegetables (Ferric iron): apple,
banana, Dark Green, Leafy Vegetables as spinach and
Dried Beans and Peas.
N.B.: Vitamin C increases iron absorption as facilitates ferric
iron to transform to ferrous iron.

Iron absorption:

Iron is taken in diet as vegetables (Fe3+) or animal diet

.(hem iron (Fe2+)

Mucosal cells in the duodenum and upper jejunum

.absorb the iron

The iron is coupled to transferrin (Tf) to be

.transported to BM for utilization or stored as ferritin

: Causes of iron deficiency

- Decreased intake of iron-containing foods

- Increased demand for iron, as in pregnancy, new
born, childhood.
- Inability to absorb iron because of damage to the
intestinal lining of stomach and small intestine.
- Increased loss of iron, due to chronic blood loss as in
peptic ulcer, hemorrhoids and parasitic infestation as
ancylostoma .
Clinical features:
1. Symptoms of the cause as gastrointestinal tract
bleeding.
2. Symptoms of anemia as pallor, easily fatigue,
palpitation.
 3. Symptoms specific to iron deficiency as pica
(preverted apetite to dirt or clay) or/and epithelial
changes as angular stomatitis, glossitis and koilonychia
( flat concave nails).
Laboratory findings:
1- Blood picture shows :
RBCs are microcytic and hypochromic (MCV
and MCH) with mild anisocytosis and
poikilocytosis.
WBCs are normal in count.
Platelets may be increased or normal.
2- Blood chemistry:
Serum iron and ferritin are decreased.
TIBC (Total Iron Binding Capacity) is increased.

Sideroblaastic
anemia
Pathogenesis: Inability of iron to be incorporated into hem
group.

Causes

.Inherited: due to genetic disorders

Acquired (more common) due to: lead poisoning,

.anti-tuberculosis drugs and alcohol

:Laboratory findings

Blood picture: Hypochromic anemia, presence of

siderocytes (basophilic stippling)

Bone marrow: pathological sideroblasts are seen

.by perls stain

.Blood chemistry: Increased or normal serum iron

.Increased or normal Ferritin

.Decreased TIBC
 Siderocyte
Sideroblast

Anemia of chronic
disorder
It is a form of anemia seen in chronic diseases due to massive
secretion of Interleukin-6.
IL-6 inhibits the release of iron from macrophages to
erythroblasts.
Lab. investigations:
- Blood film shows hypochromic microcytic anemia.
- Blood chemistry.
- Serum iron low
- TIBC is low
- Serum ferritin is normal

Thalassae
mia
Pathogenesis
A decrease in the rate of production of a certain globin chain
(, , , ).
The type of thalassemia usually carries the name of the under-
produced chain or chains.
Clinical picture of thalassemia major:
Severe pallor, jaundice, and marked hepatosplenomegaly.
Bony abnormalities, such as frontal bossing, prominent
facial bones, and dental malocclusion.
 Patients with signs of iron overload as endocrinopathy,
diabetes and thyroid disorders.

Laboratory diagnosis of thalassemia major:

Hemoglobin concentration is very low below 7 gm/dl.
Blood film shows marked anisocytosis, poikilocytosis,
microcytosis, target cells, fragmented cells and some
normoblasts.

Hemoglobin electrophoresis, in thalassemia shows;

Hb A is absent or very low
There is increase in Hb F
There is increase in Hb A2

Hereditary
Spherocytosis

Pathogenesis: There is defect in red cell membrane proteins

e.g. spectrin
Clinical features:
General features of anemia; fatigue, pallor, palpitation,

Jaundice
Enlarged spleen
Gallbladder stones
Lower leg ulcers or dermatitis (heal rapidly after
splenectomy)

Laboratory features:
CBC: HB, MCV and MCHC
Blood film shows microspherocytes
Reticulocytes
Serum indirect bilirubin
Absent serum haptoglobin.
Special tests: Osmotic fragility test: increased fragility of
RBCs
Direct antiglobin test (Coombs' test) is negative (to exclude
autoimmune hemolytic anemia which can cause a similar blood
picture).
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Important notes:
Serum ferritin measurement is the first laboratory test
recommended in the evaluation of microcytosis. Low
ferritin levels suggest iron eficiency.
Iron deficiency anemia in adult men and non-
menstruating women needs further gastrointestinal
investigation for occult blood loss.
Anemia of chronic disease is suggested with low iron
levels and decreased TIBC.
Patients with beta-thalassemia trait usually have
elevated levels of hemoglobin A2.

History and Physical Examination

 Nutritional intake (especially whole milk intake in
children)
Pica or cravings for ice are symptoms of iron
deficiency anemia.
Occupational or residential exposure to toxins, such as
lead.
Family history of anemia suggestive hemoglobin-
opathy;
Systemic symptoms of chronic infectious or
inflammatory
Gastrointestinal symptoms, including abdominal
discomfort, hematochezia (bright red rectal bleeding), in
adults.
Menstrual history in women.
Depending on the severity of anemia, the patient may
have varying levels of fatigue or dyspnea, systolic
murmur and pallor of the mucous membranes, nail beds,
and palmar creases.

Diagnostic Strategy of microcytic anemia

- After confirmation of decreased hemoglobin and
microcytosis in CBC, first order a serum ferritin level.
- If the ferritin level is low, identifying the underlying cause
of the iron deficiency anemia is the priority.
- If the serum ferritin level is not low, the next stage
evaluates the serum iron level, TIBC, and transferrin satu-
ration.
- Iron deficiency anemia is still probable if the serum iron
level and transferrin saturation are decreased and TIBC
is increased. On the other hand, if the serum iron level is
decreased and the TIBC and transferrin saturation are
decreased or normal, anemia of chronic disease
- If the diagnosis remains unclear, hemoglobin
electrophoresis can identify beta-thalassemia trait and
less common inherited causes of microcytosis (HS).
- A bone marrow biopsy can help identify sideroblastic
anemia
- A serum lead test can detect lead toxicity
Laboratory Evaluation
Red blood cell distribution width (RDW):
 - RDW measures the variation in red blood cell size.
- It is often highly increased with iron deficiency and less
with thalassemia but normal in those with anemia of
chronic disease.
Serum iron levels:
- Serum iron levels are decreased in iron deficiency.
- Serum iron levels have diurnal variations with higher
concentrations later in the day.
- Transient increases in serum iron levels may occur with
meat ingestion or iron supplementation, but do not rep-
resent an increase in iron stores as ferritin.

Serum ferritin levels:

- Ferritin is useful in differentiating iron deficiency anemia
(decreased) and anemia of chronic disease (normal)
when the serum iron level is decreased.
- Ferritin is an acute phase reactant and can be elevated
with liver disease, malignancy, and inflammation.

Total iron-binding capacity (TIBC):

- TIBC refers to the ability of unsaturated transferrin to
bind to iron.
- This measure is usually increased in iron deficiency,
decreased in anemia of chronic disease.

Hemoglobin electrophoresis, reticulocyte blood count

and peripheral blood smears are needed.
The anemia of chronic disease (Case 1)
A 10 year old boy was referred to pediatric hematology clinic
for anemia occurring on a previous blood test. Two months
earlier he had been hospitalized briefly for a high fever and
rash. While in the hospital, a CBC showed a mild microcytic
anemia (hgb 10.0 g/dL (normal 11.9-15.4 g/dL), MCV 75 fL
(normal 80-95 fL). He recovered well and was subsequently
discharged. He had since been well, with no subsequent
fevers, and no weight loss or night sweats.. His family history
was negative for any hematologic disorders or malignancies.
He had no chronic medical conditions, took no medications,
and had no known drug allergies. In clinic, he appeared
healthy, cooperative and in no distress. His skin showed no
rash, bruises, jaundice, or pallor. He had no lymphadenopathy,
scleral icterus, or conjunctival pallor. His lungs were clear with
no wheezes, and his heart sounds were normal with nomurmur.
His abdomen was soft and non-tender with no organomegaly,
although his liver was palpable and slightly tender to
palpation, but his spleen was not palpable. His extremities
were well perfused with no edema. Two months after his
original CBC his hemoglobin had risen to 11 g/dL (normal 12-15
g/dL), and MCV was 72.9 fL (normal 74- 82). His ferritin was 38
ng/mL (normal 10-200 ng/mL). Iron studies were normal as was
his hemoglobin electrophoresis and blood smear.
Thalassemia trait (Case 2)
A 23 month old girl was referred to Pediatric Hematology for
investigation of anemia. Thalassemia was suspected due to a
family history of Mediterranean anemia. Her father and some
of his family members were known to be a carrier for
thalassemia. He had been treated with high dose iron, but said
that it did not help and made him ill. His family was originally
from Sicily, where he lived for 8 years. She had no siblings. The
patient had generally been healthy, with normal growth and
development, except for a brief febrile seizure a few months
earlier. Her diet included fruits, vegetables, pasta, and lentils.
She took no medications. On exam, she appeared healthy and
alert. She was engaging and playful. She was slightly pale but
showed no signs of icterus, petechiae, or ecchymoses. She had
no adenopathy or splenomegaly. Her heart rate was regular,
and her lungs were clear. Screening lab work was remarkable
for a mild anemia that was severely microcytic with a
hemoglobin of 11 g/dL (normal 10.5-14 g/dL), MCV 60.2 fL
(normal 70-90 fL) a year earlier and more recently 9.6 g/dL and
54.9 fL. A hemoglobin electrophoresis was remarkable for an
elevated hgb A2 of 5.5 percent. Molecular studies had been
done and showed that she was a carrier of two separate
thalassemia mutations.
Severe microcytic anemia in an adult (Case 3)
A 63 year old male presented to his physician with complaints
of fatigue and shortness of breath, progressive over several
weeks. The physician noted that the patient looked pale and
ordered a complete blood count. The CBC revealed a
hemoglobin of 5.9 g/dL and an MCV of 59 fL. The physician
correctly interpreted this as a severe microcytic anemia, and
that this anemia was of relatively recent onset. The physician
considered transfusions and a prescription for oral iron as
therapy for the anemia. However, upon considering the
etiology of the anemia with the above history, he knows that
the microcytosis is not consistent with a lesion leading to acute
blood loss. Chronic blood loss is the only possibility, and that
blood loss MUST be gastrointestinal. He referred the man to a
gastroenterologist for a thorough investigation.
Milk enteropathy (Case 4)
A 14 month old boy presented to his pediatrician for a one year
well child checkup. At the visit however his parents explained
to the pediatrician that he had been pale for about the last
month or so, not feeding well, and had some pica like
behaviors. He had recently been more fussy and was sleeping
poorly. They denied any jaundice, change in bowel or urinary
habits or breathing difficulties. They denied bloody or black
stools. They reported poor feeding when offered a variety of
foods, and until very recently his diet relied heavily on milk,
and he would typically go through a gallon every other day.
The family lived in an older apartment with chipping paint that
the parents admitted the child sometimes peeled from the
walls. His growth and development had otherwise been
normal. He took nomedications and had no known allergies. He
had three healthy half siblings. His mother was of German
ancestry and had been anemic herself in the past. The father
also denied any significant family history. In clinic, the patient
was alert and active but fussy during the exam. He was
markedly pale, with no jaundice, bruising, petechiae, or rash.
His tympanic membranes and oropharynx were clear. He had
no adenopathy. His lungs were clear with no wheezes, and
heart sounds were normal with no murmurs. His abdomen was
soft and nontender with no hepatosplenomegaly. His
extremities were well perfused with no edema. Blood work was
remarkable for a hemoglobin of 4.7 g/dL and MCV of 63 g/dL, a
severe (and severely microcytic) anemia. His CBC was
otherwise unremarkable except for red cell morphologic
abnormalities consistent with severe iron deficiency. A serum
lead level was only 4 mcg/dL. The patient had a severe
microcytic, hypochromic anemia, but was well compensated
with no sign of heart failure. His parents were instructed to
stop his milk entirely and he was started on therapeutic iron
supplements. They were instructed that concomitant intake of
orange juice would aid absorption of the iron. Follow-up labs
were planned to assure his anemia was improving, but the plan
was for him to continue taking the iron for several months after
his anemia resolved, in order to replenish his iron stores. Milk
could be added back to the diet, but only with meals, as soon
as the anemia had begun to improve.