Approach to Anemia

Dr Rajendra Tamrakar
• Evaluation for anemia is one of the most
common problems seen in clinical practice
• The evaluation may be straightforward in an
otherwise healthy individual with a single
cause of anemia
• In many cases the cause is not readily
apparent and multiple conditions may be
contributing
 Specific causes of Anemia
• Iron deficiency
• B12 and folate deficiency
• Chronic disease/ Inflammation
• Hemolytic anemia
• Drug induced
• Myelodysplastic syndrome
• Hemoglobinopathies
• Aplastic anemia
• Microangiopathic hemolytic anemia
• Older adults
• Individuals with heart failure
• Children
 Definition
• A reduced absolute number of circulating red
blood cells
• A reduction in one or more of the major red blood
cell (RBC) measurements obtained as a part of the
complete blood count (CBC): hemoglobin
concentration, hematocrit (HCT), or RBC count
• World Health Organization (WHO) criteria for
anemia in men and women are <13 and <12 g/dL,
respectively
Normal values for peripheral blood
 Red Blood Cells Indices
• The RBC indices describe the size, shape, and
hemoglobin content of RBCs, as well as the
uniformity of the RBC population
 RBC indices: MCV
• Mean corpuscular volume (MCV) is the
average volume (size) of the patient's RBCs
• It can be measured or calculated (MCV in
femtoliters [fL] = 10 x HCT [in percent] ÷ RBC
[in millions/microL])
• Anemia can be classified based on whether
the MCV is low, normal, or elevated
 RBC indices: MCH
• Mean corpuscular hemoglobin (MCH) is the average
hemoglobin content in a RBC
• It is calculated (MCH in picograms [pg]/cell =
hemoglobin [in g/dL] x 10 ÷ RBC [in
millions/microL]
• A low MCH indicates decreased hemoglobin
content per cell, and is typically reflected in
hypochromia on the peripheral blood smear
• This may be seen in iron deficiency and
hemoglobinopathies like the thalassemias
 RBC indices: MCHC
• Mean corpuscular hemoglobin concentration
(MCHC) is the average hemoglobin
concentration per RBC
• It is calculated as (MCHC in grams [g]/dL =
hemoglobin [in g/dL] X 100 ÷ HCT [in percent])
• Very low MCHC values are typical of iron
deficiency anemia, and very high MCHC values
typically reflect spherocytosis or RBC
agglutination
 RBC indices: RDW
• RDW – Red cell distribution width (RDW) is a measure of the
variation in RBC size, which is reflected in the degree of
anisocytosis on the peripheral blood smear
• A high RDW implies a large variation in RBC sizes, and a low
RDW implies a more homogeneous population of RBCs
• RDW is calculated as the coefficient of variation (CV) of the red
cell volume distribution (RDW = [standard deviation/MCV] x
100).
• A high RDW can be seen in a number of anemias, including
iron deficiency, myelodysplastic syndrome, and
hemoglobinopathies, as well as in patients with anemia who
have received transfusions
Hemopoesis
 Life cycle
• The reticulocyte retains its ribosomal network
(and its staining characteristics) for
approximately four days
• Three days are generally spent in the bone
marrow and one day in the peripheral blood
• The resulting mature RBC circulates for 110 to
120 days
 Life cycle
• Under steady state conditions, the rate of RBC
production equals the rate of RBC loss
• Assuming, for ease of calculation, a survival of
mature RBC of 100 days, 1 percent of RBCs will
be removed from the circulation each day
• To achieve a constant RBC mass, RBC losses
must be replaced with an equal number of
reticulocytes during the same time period
• Reticulocytes can be enumerated manually
after supravital staining of a blood sample
with dyes such as new methylene blue
• Reticulocytes can be appreciated on a
standard blood smear stained with Wright-
Giemsa as RBC with a blue tint
(polychromatophilia) that are larger than
mature RBC, with irregular borders and a lack
of central pallor
 Clinical features
• Symptoms related to anemia can result from
two factors:
– Decreased oxygen delivery to tissues and,
– In patients with acute and marked bleeding, the
added insult of hypovolemia
 Causes of Anemia
• Two approaches
– A kinetic approach, addressing the mechanism(s)
responsible for the fall in hemoglobin
concentration
– A morphologic approach categorizing anemias via
alterations in red blood cell (RBC) size (ie, mean
corpuscular volume) and the reticulocyte response
 Kinetic approach
• Anemia can be caused by three independent
mechanisms:
– Decreased RBC production
– Increased RBC destruction
– Blood loss
 Classification according to mechanism of
production
• Blood loss • Impaired red cell
• Hemolytic anemia production
– Intrinsic abnormalities of – Disturbance of
RBC proliferation and
• Hereditary differentiation of stem
• Acquired cells
– Extrinsic – Disturbance of
• Antibody mediated proliferation and
– Autoimmune maturation of
– Alloimmune erythroblast
• Mechanical trauma
• Infections
 Morphologic approach
• According to measurement of RBC size, as
seen on the blood smear and as reported by
automatic cell counter indices
• RBCs larger than the nucleus of a small
lymphocyte on a peripheral smear are
considered large or macrocytic, while those
that appear smaller are considered small or
microcytic
 Classification according to MCV
• Hypochromic microcytic with a low MCV
• Normochromic normocytic with a normal
MCV
• Macrocytic with a high MCV
Classification of anemia
 Iron deficiency anemia
• Inadequate iron for haemoglobin synthesis
– Blood loss
– Increased demands such as growth and pregnancy
– Decreased absorption (e.g. post-gastrectomy)
– Poor intake
 Causes of IDA
• Increased Demand for Iron
– Rapid growth in infancy or adolescence
– Pregnancy
– Erythropoietin therapy
• Increased Iron Loss
– Chronic blood loss
– Menses
– Acute blood loss
– Blood donation
– Phlebotomy as treatment for polycythemia vera
• Decreased Iron Intake or Absorption
– Inadequate diet
– Malabsorption from disease (sprue, Crohn's disease)
– Malabsorption from surgery (postgastrectomy)
– Acute or chronic inflammation
 Macrocytosis without megaloblastic changes

• Physiological: Pregnancy, Newborn

• Alcohol excess
• Liver disease
• Reticulocytosis
• Hypothyroidism
• Hematological disorders (e.g. aplastic anaemia,
sideroblastic anaemia, pure red cell aplasia)
• Drugs (e.g. cytotoxics - azathioprine)
 Megaloblastic anemia
• A heterogeneous group of disorders that
share common morphologic characteristics:
– large cells with an arrest in nuclear maturation

• Presence in the bone marrow of erythroblasts

with delayed nuclear maturation because of
defective DNA synthesis
 Megaloblastic anemia
• Associated with severe anemia and
pancytopenia, gastrointestinal dysfunction
and glossitis, personality changes, psychosis,
and neurological disorders

• A peripheral smear may reveal

macroovalocytes, a characteristic of
megaloblastosis
Causes of vitamin B12 deficiency
 Evaluation of patient
• Anemia is one of the major signs of disease
• It is never normal and its cause(s) should
always be sought
• The history, physical examination, and simple
laboratory testing are all useful in evaluating
the anemic patient
 Questions to be answered
• Is the patient bleeding (now or in the past)?
• Is there evidence for increased red blood cell
(RBC) destruction (either intravascular or
extravascular)?
• Is the bone marrow suppressed? If so, why?
• Is the patient iron deficient? If so, why?
• Is the patient deficient in folate or vitamin
B12? If so, why?
 History
• Is there a recent history of loss of appetite, weight
loss, fever, and/or night sweats that might indicate
the presence of infection or malignancy?
• Is there a history of, or symptoms related to, a
medical condition that is known to result in
anemia (eg, tarry stools in a patient with ulcer-type
pain, significant blood loss from other sites,
rheumatoid arthritis, renal failure)?
• Is the anemia of recent origin, subacute, or
lifelong?
 History
• Patient's ethnicity and country of origin may
be helpful, as the thalassemias and other
hemoglobinopathies are particularly common
in patients from the Mediterranean littoral,
Middle East, sub-Saharan Africa, and
Southeast Asia
• Use of medications, both prescribed and over-
thecounter, should be examined in some
detail
 History
• Specific questions should be asked about the use of
alcohol, questions should be asked about the use of
alcohol, aspirin, and nonsteroidal antiinflammatory
drugs
• A past history of blood transfusions, liver disease,
treatment of the patient (or other family members) with
iron or other hematinics, herbal preparations, and
exposure to toxic chemicals in the workplace or
environment should also be obtained.
• An assessment of nutritional status is especially
important in older adults and alcoholics
 Physical examination
• Pallor
• Jaundice
• Other physical findings
– Presence or absence of lymphadenopathy,
hepatosplenomegaly, and bone tenderness,
especially over the sternum
– Bone pain may signify expansion of the marrow
space due to infiltrative disease, as in chronic
myeloid leukemia, or lytic lesions, as in multiple
myeloma or metastatic cancer
 Physical examination
• Signs of other hematologic abnormalities,
including petechiae due to thrombocytopenia,
ecchymoses, and other signs of bleeding due to
abnormalities of coagulation
• One should also look for signs and symptoms of
recurrent infections secondary to neutropenia or
immune deficiency states
• Stool obtained during the examination should
always be tested for the presence of occult blood
 Laboratory evaluation
• CBC with platelets, WBC differential, and
reticulocytes
• Peripheral smear
• Bone marrow examination
 Evaluation for iron deficiency
• The plasma levels of iron, iron binding
capacity (transferrin), transferrin saturation,
and ferritin should be measured
Stages of IDA
 Differential diagnosis
Tests Iron Deficiency Inflammation Thalassemia Sideroblastic
Anemia
Smear Micro/hypo Normal Micro/hypo with Variable
micro/hypo targeting
SI <30 <50 Normal to high Normal to high
TIBC >360 <300 Normal Normal
Percent <10 10–20 30–80 30–80
saturation
Ferritin (g/L) <15 30–200 50–300 50–300
Hemoglobin Normal Normal Abnormal with Normal
pattern on thalassemia;
electrophoresis can be normal
with thalassemia
 Evaluation for hemolysis
• Increase in the serum lactate dehydrogenase
(LDH) and indirect bilirubin concentrations
and a reduction in the serum haptoglobin
concentration
• Intravascular hemolysis — Plasma and urinary
hemoglobin and urinary hemosiderin should
be measured
THANK YOU