Medicine 1 21

Anemia
By: Dr. Aliaa Abd-ElFatah

Objectives :
● Introduction to hematopoiesis
● Define anaemia
● Describe symptoms and signs of anaemia
● Identify types of anaemia
● Recognize the diagnosis of each type of anaemia
● Develop treatment plans for different anaemic conditions
● Provide health education for prevention and management of different types of anaemia

Introduction to hematopoiesis
- It means production of blood cells. Intrauterine, it begins in the yolk sac of 14-20 days
human embryo. The fetal liver becomes the main site of hematopoiesis in the second
trimester of pregnancy and the fetal bone marrow in the third trimester.
- The majority of hematopoietic cells in the yolk sac and fetal liver are erythroblasts. The
embryonic hemoglobins are: Gower 1 (ξ2 ε2 ), Gower 2 (α2 ε2) and Portland 1 (δ2 γ2) are
synthesized by erythroblasts in the yolk sac, fetal hemoglobin (HbF,α2 γ2 )by erythroblasts
in the fetal liver, and both HbF and adult Hb (HbA, α2 β2 ) by erythroblasts in the fetal
bone marrow. The main site of granulocytopoietic activity in intrauterine life is the fetal
bone marrow.
- After birth, the marrow is the sole site of hemopoiesis in healthy individuals.
- During the first 4 years of life, nearly all the marrow cavities contain active red
hematopoietic marrow with very small fat cells. Thereafter, increasing numbers of fat cells
appear in certain marrow cavities. By the age of 25 years, the only sites of active
hematopoiesis are: skull bones, ribs, sternum, scapulae, clavicles, vertebrae, pelvis, the
upper half of the sacrum and proximal ends of the shafts of the femur and humerus. All
the remaining marrow cavities contain yellow fatty marrow.

1 Edited by: Co-MT

 Medicine 1 21

Definition of anemia
- Anaemia is defined as a low haemoglobin (Hb) concentration, and may be due either to a
low red cell mass or increased plasma volume eg in pregnancy). A low Hb (at sea level) is
<135g/L for men and <115g/L for women.
- Anaemia may be due to reduced production or increased loss of RBCS and has many
causes. These will often be distinguishable by history, examination, and inspection of the
blood film.
Symptoms of anemia
Due to the underlying cause or to the anaemia itself:

● Fatigue ● Headache
● Dyspnoea ● Tinnitus
● Faintness ● Anorexia
● Palpitations ● Angina if there is pre-existing coronary
artery
Signs
May be absent even in severe anaemia.
● There may be pallor (eg of the conjunctivae) although this is not a reliable sign).
● In severe anaemia (Hb <80g/L), there may be signs of a hyperdynamic circulation, eg
tachycardia, flow murmurs (ejection-systolic loudest over apex), and cardiac enlargement;
or retinal haemorrhages (rarely).
● Later, heart failure may occur: here, rapid blood transfusion can be fatal.

2 Edited by: Co-MT

 Medicine 1 21

Types of anemia
The first step in diagnosis is to look at the mean cell volume (MCV). Normal MCV is
76–96 femtolitres (1015 fL = 1L).

Low MCV (microcytic anaemia):

1. Iron-deficiency anaemia (IDA), the most common cause
2. Thalassaemia (suspect if the MCV is ‘too low’ for the Hb level and the red cell count is
raised, though definitive diagnosis needs DNA analysis).
3. Sideroblastic anaemia (very rare).
● NB: there is iron accumulation in the last two conditions, and so tests will show
increased serum iron and ferritin with a low total iron-binding capacity (TIBS)

Normal MCV (normocytic anaemia):

1. Acute blood loss.
2. Anaemia of chronic disease (or decrease MCV).
3. Bone marrow failure.
4. Renal failure
5. Hypothyroidism (or increase MCV)
6. Haemolysis (or increase MCV).
7. Pregnancy.
NB: if decrease wcc or decrease platelet in normocytic anaemia, suspect marrow failure

High MCV (macrocytic anaemia):

1. Vitamin B12 or folate deficiency.
2. Alcohol excess or liver disease.
3. Reticulocytosis (eg with haemolysis).
4. Cytotoxics, eg hydroxycarbamide
5. Myelodysplastic syndromes.
6. Marrow infiltration.
7. Hypothyroidism.
8. Antifolate drugs (eg phenytoin).

Haemolytic anaemias:
● These do not fit into the above-mentioned classification as the anaemia may be
normocytic or, if there are many young (hence larger) RBCS and reticulocytes, macrocytic.
● Suspect if there is a reticulocytosis (>2% of RBCS; or reticulocyte count >100≈109 /L),
mild macro cytosis, decrease haptoglobin, increase bilirubin, increase LDH, or increase
urobilinogen.
● These patients will often be mildly jaundiced (but note that haemolysis causes pre-
hepatic jaundice so there will be no bilirubin in their urine).

3 Edited by: Co-MT

 Medicine 1 21
Does the patient need a blood transfusion?
 Probably not if Hb >70g/L. Chronic anaemia in particular can be well-tolerated (though
it is crucial to ascertain the cause), and in IDA iron supplements will raise the Hb more
safely and cost-eff ectively.
 In acute anaemia (eg haemorrhage with active peptic ulcer), transfusion for those with
Hb <70g/L may be indicated.
 Other factors to consider include comorbidities (particularly IHD) and whether the
patient is symptomatic.
 In severe anaemia with heart failure, transfusion is vital to restore Hb to a safe level,
eg 60–80g/L, but this must be done with great care.
 Give it slowly with 10-40mg furosemide IV/PO with alternate units (dose depends on
previous exposure to diuretics; do not mix with blood).
 Check for signs of worsening overload: rising JVP and basal crackles: in this eventuality,
stop and treat.

Red cell distribution width (RCDW or RDW)

 In health or in unifactorial anaemia, all the red cells in a sample are about the same
size, and the graph of their volume distribution forms a narrow peak.
 In mixed anaemias, however, this peak broadens, reflecting an abnormally large RDW-
this may be the first clue to dual pathology.
 In coeliac disease, for example, poor absorption of iron (decrease MCV) and folate
(increase MCV) may occur simultaneously, resulting in a combination of microcytes
and macrocytes in the circulation.
 The visual analogue of this is anisocytosis on a blood film. The laboratory measure is a
increase RDW, where RDW = the standard deviation of MCV divided by the mean MCV,
multiplied by 100.
 Reference interval: 11 . 5–14 . 6%. If the MCV is high and the RDW is normal, the cause
is likely to be alcohol, liver disease, or a marrow problem (chemotherapy or aplastic
anaemia)

Iron-deficiency anaemia (IDA)

This is common (seen in up to 14% of menstruating women).
Causes:
 Blood loss, eg menorrhagia or GI bleeding (upper and lower)
 Poor diet or poverty may cause IDA in babies or children (but rarely in adults).
 Malabsorption (eg coeliac disease) is a cause of refractory IDA.
 In the tropics, hookworm (GI blood loss) is the most common cause.
Signs:
Chronic IDA (signs now rare): koilonychia, atrophic glossitis, angular cheilosis, and, rarely,
post-cricoid webs (Plummer–Vinson syndrome).

4 Edited by: Co-MT

 Medicine 1 21

Tests:
To diagnose IDA
1. Blood film:
microcytic, hypochromic anaemia with anisocytosis and poikilocytosis.
Decrease MCV,
Decrease MCH, and
Decrease MCHC.
2. Iron profile:
Confirmed by decrease ferritin (also decrease serum iron with increase TIBC, but these
are less reliable).
NB: ferritin is an acute phase protein and increase with inflammation, eg infection,
malignancy.
• Transferrin is also increase in IDA but is less affected by inflammation.

To search for the cause of IDA

• Check coeliac serology in all: if negative then refer all males and females who are not
menstruating for urgent gastroscopy and colonoscopy.

5 Edited by: Co-MT

 Medicine 1 21
Consider stool microscopy for ova if relevant travel
history.
Faecal occult blood is not recommended as
sensitivity is poor.
• IDA with no obvious source of bleeding mandates
careful GI workup. 2

Treatment:
 Treat the cause. Oral iron, eg ferrous sulfate 200mg/8h PO.
 Side Effects: nausea, abdominal discomfort, diarrhoea or constipation, black stools.
 Hb should rise by 10g/L/ week, with a modest reticulocytosis (young RBC).
 Continue for at least 3 months after Hb normalizes to replenish stores.

 IV iron is only indicated if the oral route is impossible or ineffective, eg functional

iron deficiency in chronic renal failure, where there is inadequate mobilization of iron
stores in response to erythropoietin therapy.
 The usual reason that IDA fails to respond to iron replacement is that the patient has
rejected the pills—check compliance.

 Is the reason for the problem GI disturbance? Altering the dose of elemental iron
with a different preparation may help.
 Alternatively, there may be continued blood loss, malabsorption, anaemia of chronic
disease; or misdiagnosis, eg when thalassaemia is to blame.

Anaemia of chronic disease (secondary anaemia)

• The commonest anaemia in hospital patients (and the 2nd commonest, after IDA,
worldwide).
• It arises from three problems (in which the polypeptide, hepcidin, plays a key role):
1. Poor use of iron in erythropoiesis.
2. Cytokine-induced shortening of RBC survival.
3. Decrease production of and response to erythropoietin.

6 Edited by: Co-MT

Medicine 1 21

Causes:
Many, eg chronic infection, vasculitis, rheumatoid, malignancy, renal failure.
Tests:
Ferritin normal or increase in mild normocytic or microcytic anaemia (eg Hb >80g/L; see
table 8.1).
Check blood film, Vitamin B12, folate, TSH, and tests for haemolysis.
Treatment:
• Treating the underlying disease may help (eg in 60% of patients with RA), as may
erythropoietin (SE: flu-like symptoms, hypertension, mild rise in the platelet count and
thromboembolism).
• Also effective in improving quality of life in malignant disease.
• IV iron can safely overcome the functional iron deficiency.
• Hepcidin inhibitors and inflammatory modulators show promise.

Sideroblastic anaemia
• Microcytic anaemia does not always mean iron deficiency! 20% of older people with an
MCV <75 fL are not iron deficient.
• Think of sideroblastic anaemia whenever microcytic anaemia is not responding to iron.
• This condition is characterized by ineffective erythropoiesis, leading to increase iron
absorption, iron loading in marrow ± haemosiderosis (endocrine, liver, and heart damage
due to iron deposition
Causes:
• Congenital (rare, x-linked) or acquired, eg idiopathic as one of the
myelodysplastic/myeloproliferative diseases, can also follow chemotherapy, anti-TB drugs,
irradiation, alcohol or lead excess.

7 Edited by: Co-MT

 Medicine 1 21
Tests:
Look for:
1. Increase ferritin
2. A hypochromic blood film
3. Disease-defining sideroblasts in the marrow

Treatment:
Remove the cause. Pyridoxine ± repeated
transfusions for severe anaemia.

Interpreting plasma iron studies

Iron TIBC Ferritin

Iron deficiency ↓ ↑ ↓
Anaemia of chronic disease ↓ Normal
Or ↑
slightly↑
Chronic haemolysis ↑ ↓ ↑

Haemochromatosis ↑ ↓(or ↔) ↑
Pregnancy ↑ ↑ ↔
Sideroblastic anaemia ↑ ↔ ↑

8 Edited by: Co-MT

 Medicine 1 21

Quiz:
1. A 39-year old women is evaluated for her Lab studies reveal a hemoglobin of 7.4g/dl,
hematocrit of 23%, MCV of 72 fl., the peripheral blood smear shows anisopikilocytosis
and central pallor >50% of RBCs size. Which of the following tests is most likely to be
abnormal in this patient?

A. Serum Ferritin.
B. Habtoglobin
C. Hemoglobin electrophoresis
D. Glucose 6 Phosphate Dehydrogenase (G6PD) enzyme level
E. Vitamin B12 level

2. Which one of the following is not suggestive of iron deficiency anemia?

A. Koilonychia
B. Pica
C. Decrease serum ferritin
D. Decrease total iron binding capacity
E. Angular stomatitis

3. A 24-year old man with a history of poorly treated chronic ulcerative colitis is found
to have anemia with Hb of 9g/dl and a reduced MCV. His serum ferritin is 250ug/L.
Which of the following is the most likely cause of his anemia?

A. Folate deficiency
B. Hemoglopanopathy
C. Chronic inflammation
D. Iron deficiency
E. Sidroblastic anemia

4. Which statement of the following regarding the anemia of CKD is not correlated with
it :

A- The degree of anemia correlates with the stage of kidney disease.

B- EPO levels are reduced
C- Ferritin is reduced
D- Is typically N-N.

9 Edited by: Co-MT