Anemia Management in Adults and Children

Haematology
Anaemia
Dr. Kofi .B. Mensah (Pharmacy Practice)

Learning objectives
• Understand the basic definition of anaemia including reference range,
global prevalence, etc.
• Understand the pathophysiology underlining anaemia.
• Understand classification of anaemia.
• Understand signs and symptoms.
• Understand laboratory findings.
• Understand the different types of anaemia.

Introduction
• Anaemia is defined as a reduction in
the concentration of circulating
haemoglobin or oxygen-carrying
capacity of blood below the level that
is expected for healthy persons or ref.
range of same age and sex in the same
environment.
• It is one of the most common clinical
and laboratory manifestations of
disease, and always requires further
investigation.
• It is not a diagnosis in itself, but rather
an objective sign of a disease or a
finding that can point to primary bone
marrow disease, dietary inadequacies
or a wide variety of systemic diseases.
Structure of haemoglobin
• Iron (Fe2+
) containing pigment called
Haem attached with protein – Globin.
• Haem is Iron –porphyrin complex
called IRON PROTOPORPHYRIN IX.
• Globin – Protein.

Sex Haemoglobin (g/dl) PCV (%)
Sex/Age
Adult males
Haemoglobin (g/dl)
13–17
PCV (%)
40–50
Adult females (nonpregnant) 12–15 38–45
Adult females (pregnant) 11–14 36–42
Children, 6–12 years 11.5–15.5 37–46
Children, 6 months–6 years 11–14 36–42
Infants, 2–6 months 9.5–14 32–42
Newborns 13.6–19.6 44–60
Normal levels of haemoglobin and packed cell volume

Pathophysiology
• In healthy adults, there is a steady-state equilibrium between the rate of
release of new red cells from the bone marrow into the circulation and
the removal of senescent red cells from the circulation.
• Erythropoietin (epo) is the main agent responsible for translating tissue
hypoxia into increased red cell production to maintain this balance.
• For anaemia to arise:
inadequate production of red cells (e.g. insufficient erythroid tissue in the
marrow or poor quality erythroid maturation).
increased rate of red cell loss (e.g. blood loss or haemolysis).

• NB: The reticulocyte count is a useful marker to differentiate anaemia caused by
failure of production from that caused by accelerated red cell destruction.
• Although the reticulocyte count is an important part of the assessment of any
patient with anaemia, it may not be straightforward to interpret. Read further.
• Other mechanisms leading to anaemia
 Blood loss
Decreased red cell lifespan (haemolytic anaemia)
mineral deficiency (iron, zinc, selenium)
Congenital defect (e.g. sickle cell disease)
infection (hookworm, schistosomiasis, malaria)
Acquired defect (e.g. Thalassaemia)
Impairment of red cell formation:
 Insufficient erythropoiesis
Ineffective erythropoiesis
Pooling and destruction of red cells in an enlarged spleen
Increased plasma volume (pregnancy)

Morphological classification of anaemia
• In terms of red cell size:
characteristic changes in the size of red cells (mean cell volume, MCV).
red blood cell distribution width(RDW):an index of RBC size variation
• Degree of haemoglobinization:
mean cell haemoglobin (MCH): the amount of hemoglobin in a single red blood cell.
MCH = (hemoglobin / RBC) x 10
mean cell hemoglobin concentration (MCHC): the average hemoglobin concentration of
packed red cells expressed as a percentage.
MCHC = (hemoglobin / hematocrit) x 100
• Different aetiologies:
Microcytic-hypochromic (low MCV and low MCH).
Macrocytic-normochromic (high MCV).
Normocytic -normochromic (normal MCV)

Microcytic-hypochromic Normocytic- normochromic Macrocytic
MCV <80fL MCV 80–95fL MCV >95fL
MCH <27pg MCH ≥27pg Megaloblastic: vitamin B12 or folate
deficiency
Non‐megaloblastic: alcohol, liver
disease, etc.
Iron deficiency Haemolytic anaemia Marked reticulocytosis.
Thalassaemia Anaemia of chronic disease Myelodysplastic syndromes
Anaemia of chronic disease Haemorrhagic anaemia
(After acute blood loss)
Acquired sideroblastic anaemia
Sideroblastic anaemia Bone marrow failure (e.g. post‐
chemotherapy, infiltration by
carcinoma, etc.)
Myxoedema.
Aplastic anaemia

Detection (signs and symptoms)
• Decreased oxygen-carrying capacity of the reduced red cell mass
resulting in decrease perfusion to non-vital tissues (e.g., skin, mucous
membranes, extremities) and vital organs (e.g., brain, heart, kidneys).
• Slowly developing anemias can be asymptomatic initially or include
symptoms such as slight exertional dyspnea, increased angina, fatigue
or malaise, palpitation, headaches, dizziness or lightheadedness, cold
hands and feet, pallor of mucous membranes or nail beds.
• In severe anaemia, symptoms include; systolic murmurs, angina
pectoris, high output congestive heart failure, pulmonary congestion,
ascites, and edema.

Physical signs
Common signs:
 Pallor of the conjunctiva, lips,
skin and mucous membranes.
Colour of the skin is unreliable
because of skin pigmentation
and the amount of fluid in the
subcutaneous tissues.
 Most reliable are the palm of the
hand, conjunctiva, and nail bed.

Detection (laboratory findings)
• A full laboratory evaluation is necessary to confirm the diagnosis, establish its
severity, and determine its cause.
• The laboratory investigation is called full/complete blood count (FBC/CBC).
• Microscopic evaluation of the peripheral blood smear can detect the presence of
macrocytic (large) RBC, which usually are present when anaemia results from a
vitamin B12 or folic acid deficiency.
• Microcytic (small) RBC usually are associated with iron deficiency anemia.
• Acute blood loss generally is associated with normocytic cells.
• When uncertainty exists or an abnormal peripheral blood smear is noted, a bone
marrow aspiration with biopsy is indicated.

Laboratory evaluation for anaemia
Workup
• Full blood count (FBC): Hgb, Hct, RBC count, red cell indices (MCV,
MCH, MCHC), WBC count (and differential)
• Platelet count
• Total iron binding capacity (TIBC)
• Red cell morphology
• Reticulocyte count
• Bilirubin and LDH
• Serum iron, serum ferritin, transferrin saturation
• Peripheral blood smear examination (blood film)
• Stool examination for occult blood
• Bone marrow aspiration and biopsy

Routine lab. Investigation- FBC/CBC
• Normal ranges may vary among age groups, institutions, and geographic locations.

Type of anaemia
Iron deficiency anemia
• Iron deficiency is a state of negative iron balance in which the daily iron intake
and stores are unable to meet the RBC and other body tissue needs.
• The body contains approximately 3.5g of iron, of which 2.5 g are found in Hgb.
• A significant amount of iron is stored as ferritin or aggregated ferritin
(hemosiderin) in the reticuloendothelial cells of the liver, spleen, and bone
marrow and by hepatocytes.
• Only a small fraction of iron is found in plasma (100 to 150 mcg/dL), and most is
bound to transferrin, the transport protein.
• About 0.5 to 1 mg/day of iron is lost from urine, sweat, and the sloughing of
intestinal mucosal cells. (men and in non-menstruating women).
• Menstruating women lose abt. 0.6% to 2.5% iron per day whiles Pregnancy and
lactation are other sources of iron loss.
• Individuals with normal iron stores absorb roughly 10% of ingested dietary iron.

Cont.
• Iron is absorbed from the duodenum and upper jejunum by an active
transport mechanism in an acidic gastric environment.
• Dietary iron is primarily in the ferric state, converted to the more
readily absorbed ferrous form in the acid environment and binds to
transferrin for its journey to the bone marrow, where it is incorporated
into the Hgb of mature erythrocytes.
• Animal sources of iron, heme iron, are better absorbed than plant
sources, non-heme iron.
• Iron deficiency anaemia is the most common nutritional deficiency
worldwide. Although it has many causes, blood loss is considered one
of the major causes.

Causes
• Blood Loss (Menstruation, gastrointestinal (e.g., peptic ulcer), trauma).
• Decreased Absorption (Medications, gastrectomy).
• Increased Requirement (Infancy, pregnant/lactating women).
• Impaired Utilization (Hereditary, Iron use).
Treatment
• Fe2+ is usually absorbed from the gut, hence satisfactory response is achieved in most patients when iron salts are given orally.
• Ferrous sulphate should be used unless gastrointestinal adverse effects are severe.
• The duration of treatment, and its success, depends on the underlying cause of the anaemia.
• Haemoglobin should rise by approximately 1 g/dL/week.
Dose: Ferrous sulphate is given at a dose of 200 mg t.i.d until anaemia is corrected and iron stores are replenished.
Read on oral Fe2+ and Parenteral iron.
• 4

Macrocytic anaemia
• Macrocytic anaemia can be divided into those showing megaloblastic
erythropoiesis and those with normoblastic erythropoiesis.
• Megaloblastic erythropoiesis describes abnormal red cell
development characterized by a lack of synchrony between the
maturation of the red cell nucleus (large immature nucleus) and its
cytoplasm.
• It arises as a consequence of disordered DNA synthesis but RNA and
protein synthesis remain unaffected, and the cytoplasm matures
normally.
• Normoblastic erythropoiesis describes the normal appearance of red
cell maturation, but may still be associated with a macrocytosis in the
peripheral blood.

• Folic acid is required for DNA synthesis.
• Vitamin B12 (cobalamin ) is needed for regeneration of
tetrahydrofolate – the form of folate that is critical for the pyrimidine
synthesis.
Causes
folic acid deficiency
 vit.B12 deficiency
inherited defects associated with decreased ability to utilize vitamin
B12 or folic acid.
• The main clinical features in more severe cases are those of anaemia.
• Anorexia is usually marked and there may be weight loss, diarrhoea or
constipation. Other particular features include glossitis, angular
cheilitis, a mild fever in the more severely anaemic patients, Loss of
position sense in 2nd toe,etc.

Treatment
• The underlying cause must be treated where possible.
• Folic acid supplementation orally is generally sufficient to treat folic
acid deficiency.
• 5mg a day for about 4–6 months replenishes depleted stores.
• B12 supplementation orally is appropriate and also improve
neurological signs.
• Hydroxycobalamin is retained in the body for longer than
cyanocobalamin and treatment can be given every 3 months.
• Given by intramuscular injection, initial dose: 1 mg every 2–3 days for
five times.
• Maintenance dose: given every 3 months.

Pernicious anemia
• Pernicious anemia can result in vitamin B12 deficiency.
• It can be caused by reduced intrinsic factor and hydrochloric acid
secretion or acquired as a result of gastrectomy, pancreatic disease,
or malnutrition.
• It occurs commonly in patients with thyrotoxicosis, Hashimoto’s
thyroiditis, vitiligo, rheumatoid arthritis, or gastric cancer.
• The onset of the pernicious anemia is insidious.
• Patients generally do not feel well for 6 to 12 months and often
complain of at least two of the following of symptoms: weakness,
sore tongue, and symmetric numbness or tingling in the extremities.
• The cause of vitamin B12 deficiency may be determined by the use of
antibody testing (anti-parietal cells and anti-intrinsic factor
antibodies).

Laboratory Evaluation
• A Full blood cell count ( FBC).
• Examination of a blood smear (peripheral smear) under a microscope,
often performed in association with a FBC.
• Blood vitamin B-12 level measurements.
• Tests for the presence of antibodies to intrinsic factor or stomach lining
cells.
• Blood levels of iron and iron-binding capacity.
• Serum folate levels (which are often reduced when vitamin B-12 levels
are low).
• Blood levels of homocysteine, which may be sensitive indicators of
vitamin B-12 deficiency.
• Finally, bone marrow aspiration or bone marrow biopsy may be
recommended in some cases if bone marrow disorders are suspected

Treatment
• Vitamin B-12 is typically given as an intramuscular injection. 1000
micrograms (1 mg) of vitamin B-12 is generally given every day for
one week, followed by 1 mg every week for four weeks and then 1 mg
every month thereafter.
• Alternatively high-dose oral vitamin B-12, since a lower-efficiency
absorption system for vitamin B-12 exists in the intestine that does
not require the presence of IF.
• The oral dose required for this type of therapy (1 to 2 milligrams/day)
is more than 200 times higher than the minimum daily vitamin B-12
requirement for adults.

Aplastic anaemia
• This occurs when cellular activity in the bone marrow is suppressed and is usually associated
with the suppression of white cell and platelet formation.
• There are two different types:
Acquired aplastic anemia
Inherited aplastic anemia
• Inherited aplastic anemia is caused by gene defects, and is most common in children and young
adults.
• Acquired aplastic anemia is more common in adults. Researchers believe something triggers
problems in the immune system.
• The possibilities include:
Viruses like HIV or Epstein-Barr
Certain medications e.g. Find out
Toxic chemicals
Radiation

common symptoms for each:
• Low red blood cell count:
Tiredness, shortness of breath, dizziness, pale skin, headaches, chest
pain, irregular heartbeat.
• Low white blood cell count: Infections, fever
• Low platelet count: easy bruising and bleeding, nosebleeds.
Treatment
• bone marrow or stem cell transplant
• Autoimmune medications to stop the attack of the immune syst. On
the bone marrow.

Haemolytic Anemia
• This is defined as anaemia that result from an increase in the rate of
red cell destruction.
• Because of erythropoietic hyperplasia and anatomical extension of
bone marrow, red cell destruction may be increased several‐fold
before the patient becomes anaemic – compensated haemolytic
disease.
• Haemolytic anaemia may not be seen until the red cell lifespan is less
than 30 days.
• In the majority of haemolytic anaemias, the macrophages in the
spleen, liver and bone marrow remove red cells from the circulation
by phagocytosis. This is termed extravascular haemolysis.
• In intravascular haemolysis, the red cells are caused to rupture and
release their haemoglobin (Hb) directly into the circulation

Classification
• (1) Hereditary haemolytic anaemias: the result of ‘ intrinsic ’ red cell
defects. Such as,
Haemoglobin (Genetic abnormalities (Hb S, Hb C).
Metabolism (G6PD deficiency).
Membrane (Immune Hereditary spherocytosis).
• (2) Acquired haemolytic anaemias: the result of an extracorpuscular’
or environmental change. Such as,
Infections (Malaria, clostridia)
Chemical and physical agents (drugs, industrial/domestic substances)
Secondary (Liver and renal disease)
Autoimmune(Warm antibody type, Cold antibody type)

Laboratory evidence
• Many tests are used to diagnose hemolytic anemia. These tests can help
confirm a diagnosis, look for a cause, and find out how severe the condition
is.
Test
• FBC-the first test used to diagnose anemia.
• Reticulocyte count (the number of young red blood cells in the blood)-
indicative of whether the bone marrow is making red blood cells at the
correct rate.
• Peripheral smear (microscopic examination)- Some types of hemolytic
anemia change the normal shape of red blood cells.
• Coombs' test: To check whether the body is making antibodies to destroy
red blood cells.
• Haptoglobin, bilirubin, and liver function tests- low level of haptoglobin in
the bloodstream is a sign of hemolytic anemia. High levels of bilirubin in
the bloodstream may be a sign of hemolytic anemia (rule out liver disease).

Cont.
• Hemoglobin electrophoresis- This test looks at the different types of
hemoglobin in your blood. It can help diagnose the type of anemia
you have.
• Paroxysmal nocturnal hemoglobinuria- A rare acquired, life-
threatening disease characterized by destruction of red blood cells.
• Osmotic fragility test- This test looks for red blood cells that are more
fragile than normal. These cells may be a sign of hereditary
spherocytosis (an inherited type of hemolytic anemia).
• Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Urine Test- Presence of free hemoglobin.
• Bone marrow tests- Aspiration and biopsy.

Mandatory test
• Newborn Testing for Sickle Cell Anemia and G6PD Deficiency- It is a
requirement to screen for sickle cell anemia as part of newborn
screening programs. Some hospital/health facilities also mandate
screening for G6PD deficiency.
• Diagnosing these conditions as early as possible is important so that
children can get proper treatment.

Anemia of chronic disease (ACD)
• ACD refers to a mild to moderate anemia associated with a number of disorders (e.g., rheumatoid
arthritis, chronic infections, chronic renal failure, acquired immunodeficiency syndrome [AIDS],
neoplastic disease).
• Most often, ACD is a normochromic-normocytic anemia, although red cells may be hypochromic and
microcytic in some patients.
• Serum iron and total iron-binding capacity are most often decreased, whereas iron stores (serum
ferritin) are usually normal or increased.
Signs and symptoms : Same as iron deficiency anaemia.
Feeling tired or weak.
Having pale skin.
Having shortness of breath.
Sweating.
Being dizzy or feeling faint.
Rapid heartbeat.
Having headaches.

Pathogenesis
• Pathogenesis is not well understood, inflammatory cytokines
(Interferon-α(IFN-α), -β (IFN-β), -γ (IFN-γ), tumor necrosis factor-α)
are thought to play a major role through multiple mechanisms.
• Competition for EPO receptors by cytokines may possibly lead to EPO
resistance.
• Inhibition of hepatic and renal expression of EPO messenger RNA
(mRNA), further contributing to the development of ACD.
• Interleukin-6 (IL-6) promotes expression of hepcidin, which alters iron
hemostasis by decreasing duodenal iron absorption and inhibiting the
release from iron stores. This affect bone morrow erythrocyte
production.

Treatment
• Management of mild to moderate ACD usually focuses on the
underlying disease process.
• Patients may require blood transfusions for symptomatic anemia.
Unless a concurrent deficiency of vitamin B12, folate, or iron exists,
administration of vitamin supplements is not of value.
• Recombinant human EPO (rhEPO) has been used successfully to treat
ACD in patients with RA, AIDS, some neoplastic diseases, and chronic
kidney disease.
• Patients are less likely to respond to rhEPO if baseline serum EPO and
inflammatory cytokine levels are elevated.
• Although serum iron often is decreased, reticuloendothelial iron
stores are usually adequate, and treatment with iron is not
warranted.

Anemia Management in Adults and Children

Anemia Management in Adults and Children

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