 Haematopoiesis: it is the production of

erythrocytes, platelets, and leukocytes from

undifferentiated stem cells.
 The haemtopoietic machinary reside in the
bone marrow in adults.
 It requires a constant supply of essential
nutrients – iron, vit B12, folic acid and
presence of hematopoietic growth factors
 Anemia: anemia is a common clinical
condition that is caused by an acquired or
hereditary abnormality of RBCS or it
precursor, or it may be a manifestation of an
underlying non hematologic disorder.
 Anaemia is defined as a decrease in the
circulating RBC mass; the usual criteria are a
Hb of less than 12G/dl in women and less
than 14G/dl in men.
 Signs and Symptoms:
 Patients with an Hb less than 7G/dl will have
symptoms of tissue hypoxia( fatigue,
headache, dyspnea, pallor, angina,
tachycardia, visual impairment, syncopy,
lymphadenopathy,hepatic and or splenic
enlargement, bone tenderness, blood loss in
feces, neurologic symptoms.
 Classification of anemia:
 Anemia associated with decrease RBC
production for e.g.
1. iron deficiency anemia,
2. megalobl.anemia,
3. Thalassemia,
4. anemia due to chronic disease
5. renal failure.
 Anemia due to increased RBC destruction:
1. Hemolytic anemia,
2. Sickle Cell anemia
 Iron: Total quantity of iron in the body is 4-
5G, 65-70% in the form of Hb in RBC, 4% in
myoglobin, 1% in various heme compound,
15-30% stored in the form of ferritin and
hemosiderin in RE( reticulo endothelial )
system, liver, spleen, intestinal mucosa and
bone marrow

 Iron is required for Hb production, in the
absence of adequate iron, small red cells
with insufficient Hb are formed, giving rise
to microcytic hypochromic anaemia.
 Vit B12 and folic acid are required for
normal DNA synthesis. Deficiency of either
of these vitamins results in impaired
production and abnormal maturation of
RBCS giving rise the characteristic blood
and bone marrow picture known as
megaloblastic anaemia.
 Erythropoeitin and colony stimulating factors are hormones
that regulate blood cell development and proliferation in the
bone marrow.
 Chief source of iron is meat.
 Iron deficiency occur due to
a) inadequate dietary intake as in vegetarians,
b) malnourished pts.
c) due to blood loss a in women in heavy menstruation
d) when iron requirement is increased as in pregnancy and in
growing children.

 ‫ه‬
 Iron forms heme, which combined with
proteins globin and form hemoglobin, Hb
binds oxygen(in the lungs) and transport it in
the tissues.
 Iron preparation:
 1. Oral iron,
 2. Parenteral iron
 1. oral iron
 A) Ferrous sulfate - 325mg - 65mg
elementaliron
 B )Ferrous gluconate - 320mg -37mg
elem.iron
 C) Ferrous fumarate - 325mg - 106mg
elem.iron
 2. Parenteral iron: iron dextran 50mg
elem.iron/ml
 Pharmacokinetics:
 Absorption: iron( Fe++) absorb from
duodenum and upper jejenum →Fe+++
(ferric) in the intestinal mucosal cell.
 Ferric iron binds with transferrin in plasma
and transported in other tissues and stored
as ferritin and hemosiderin form.
 About 10 -20% of dietary iron is absorbed,
for e.g. a standard diet if contain 10-15mg
of iron, only 1mg is absorbed. Absorption
↑when iron requirement is ↑ as in
pregnancy, menstruation, growing children
 Distribution: ferric from iron store sites
through transferrin goes in the RBCS.
 This complex bind with receptor on
developing red cells in Bone marrow, iron
released in the cell, transferrin and transferrin
receptor are then recycled, providing an
efficient mechanism for incorporating iron
into hemoglobin in developing cells
 Storage: ferritin and hemosiderin form in
mucosal cells, liver, spleen, and bone marrow
 Elimination: minimal amount (about
1mg/day) are lost in sweat, saliva, and in
exfoliated skin and intestinal mucosal cell.
 Clinical use of iron:
 Iron deficiency anaemia is the only indication
for the use of iron
 Iron deficiency is commonly seen in
premature infants, children during rapid
growth, pregnant and lactating mothers,
patients with small bowel disease that results
in generalized malabsorption.
 The most common cause of iron deficiency
anaemia in adults is blood loss.
 As iron deficiency develops: storage iron
decreases and then disappears, serum ferritin
decreases, then serum iron decrease, TIBC ↑.
 200- 400mg oral elemental iron daily should
be given to correct anaemia (25% absorbed
,so 50-100mg iron can be incorporated in
Hb).
 Treatment should be continue for 3-6
months, this not only correct the anaemia but
will replenish iron stores. (Hb should reach
normal level in 1-3 months).
 Failure to respond to oral iron therapy may be
due to incorrect diagnosis.
 Adverse effects:
 Due to oral iron therapy;
 Nausea, epigastric discomfort, abdominal
cramps, constipation, diarrhea, black stool.
 They may be minimized by lowering the daily
dose or by taking iron tablets immediately
after or with meals.
 Parenteral iron therapy:
 1. It should be reserved for patients with
documented iron deficiency unable to tolerate
or absorb iron ( pts. With post gastrectomy,
previous small bowel resection,
malabsorption syndrome.
 2. Pts. With extensive chronic blood loss who
can not be maintained with oral iron alone.
 Iron dextran (ferric hydroxide + dextran),
50mg elemental iron/ml
 Route of administration: I/M, or by I/V
infusion in 1-2 hours.
 Most adults needs about 1-2 G (20-40ml)
iron dextran for iron deficiency anaemia.
 Test dose : test dose of small amount should
be given before I/M or I/V
 Adverse effects:
 Local pain, tissue staining( brown
discoloration of tissues overlying the inj.
site), headache, fever, arthralgia, nausea,
vomiting, bronchospasm, urticaria,
anaphylaxis, and death
 Iron toxicity: it is seen in young children who
have ingested a no. of iron tablets( more than
10 tablets). Adults are able to tolerate large
doses of iron.
 Large amount of oral iron cause;
 Necrotizing gastroenteritis, vomiting,
abdominal pain, bloody diarrhea, dyspnea,
metabolic acidosis, coma and death.
 Treatment of acute toxicity:
1. Whole bowel irrigation should perform
2. Deferoxamine- potent iron chelating,
it binds iron that has already been absorbed and to
promote its excretion in urine and feces
 Supportive therapy for GIT bleeding ,
metabolic acidosis and shock
 Chronic toxicity: known as
hemochromatosis, when excess iron is
deposited in heart, liver, pancreas and other
organs cause organ failure and death.
 It occurs in patients with inherited
hemochromatosis (excessive iron
absorption in pts. Who receive many red cell
transfusions for long period
 Treatment: intermittent phlebotomy, 1 unit
of blood removed/weekly
 Iron chelating agent ( deferoxamine i/v)
 Deferoxamine:
◦ Poorly absorbed when given orally and may
increase iron absorption by this route
◦ Given I/M or preferably I/V
◦ Metabolized and excreted in urine (turn urine color
orange red).
 Adverse effects:
 Rapid I/V administration → hypotension
 Idiosyncratic response such as flushing,
erythema, intestinal irritation, urticaria
 Acute respiratory distress syndrome may
occur if I/V infusion lasting longer than 24
hours
 Neurotoxicity after long term therapy of iron
overload condition
 VITAMIN B12
 Vitamin B12 ( cobalamine), a cobalt containing
molecule is along with folic acid, a cofactor in the
transfer of 1- carbon units, a step necessary for
the synthesis of DNA.
Impairment of DNA synthesis affects all cells, but
because red blood cells must be produced
continuously, deficiency of either vitamin B12 or
folic acid usually manifests first as anaemia
(megaloblastic anaemia)
 In addition Vit. B12 deficiency can cause
neurologic defects, which may become
irreversible if not treated promptly
 Pharmacokinetics:
◦ Vit B12 is produced only by bacteria. It is absorbed
from the GIT in the presence of intrinsic factor, a
product of the parietal cells of the stomach.
 Plasma transport is accomplished by binding
to transcobalamin II.
 Vit B12 is stored in the liver in large amounts;
a normal individual has enough to last 5
years.
 It is available in 2 forms
 1. cyanocobalamine, 2. hydroxy cobalamine
has a longer circulating half life.
 Pharmacodynamics:

◦ Vit B12 IS ESSENTIAL IN 2 REACTIONS:

 Pharmacodynamics:
◦ Vit B12 IS ESSENTIAL IN 2 REACTIONS:
1. Conversion of methyl malonyl – coenzyme A(co A to
succinyl – co A, and conversion of homocystein to
methionine.
2. The second reaction is linked to folic acid
metabolism and synthesis of deoxythymidylate (d
TMP), a precursor required for DNA synthesis
 In Vit B 12 deficiency , folates accumulates as
N – methyl tetrahydrofolate, the supply of
tetrahydrofolate is depleted; and the
production of RBCS slows.
 administration of folic acid to pts. With Vit
B12 deficiency helps refill the
tetrahydrofolate pool and partially or fully
corrects anaemia
 However exogenous folic acid does not
correct the neurologic defects of Vit B12
deficiency
 Clinical uses and toxicity:
 Both agents have equivalent effects.
 1. Treatment of naturally pernicious anaemia
 2. anaemia caused by gastric resection
 Because Vit B12 def. anaemia is almost
always caused by inadequate absorption,
therapy should be by replacement of
VitB12,using parenteral therapy. No
significant toxicity of VitB12 occurred
 Folic acid:
 Like Vit B12 folic acid is required for normal
DNA synthesis, and its def. usually presents
as megaloblastic anaemia.
 In addition deficiency of folic acid during
pregnancy increase the risk of neural tube
defects in the fetus
 Pharmacokinetics:
 Folic acid is readily absorbed from GIT. Only
modest amount are stored in the body, so a
decrease in dietary intake is followed by
anemia within few months
 Pharmacodynamics:
 Folic acid is converted to tetrahydrofolate by
the action of dihydrofolate reductase
 One important set of reactions involving
tetrahydrofolate and dihydrofolate constitutes
the dTMP cycle, which supplies the dTMP
required for DNA synthesis.
 Rapidly dividing cells are highly sensitive to
folic acid deficiency. For this reason,
antifolate drugs are useful in the treatment of
various infections and cancers
 Clinical use and toxicity:
 Folic acid deficiency is most often caused by
dietary insufficiency and malabsorption.
 Anemia resulting from folic acid deficiensy is
readily treated by oral folic acid.
 Maternal folic acid def. is associated with
increased risk of neural tube defects in the
fetus, folic acid supplementation is
recommended prior to and during pregnancy
 Folic acid supplements will correct the
anemia but not the neurologic deficits of Vit
B12 deficiency.
 Therefore Vit B12 deficiency must be ruled
out before one selects folic acid as the sole
therapeutic agent in the treatment of patients
with megaloblastic anaemia.
 Folic acid has no recognized toxicity
 Erythropoietin:
 ERYTHROPOIETN is produced by the kidney
 Reduction in its synthesis is responsible for
anemia of renal failure
 Activation of receptors on erythroid
progenitors in the bone marrow, it stimulates
the production of red cells and increases their
release from B. M
Erythropoietin is used for anemia associated
with renal failure and some time effective for
patients with other forms of anemia eg.
primary bone marrow disorder or anemia
secondary to cancer chemotherapy or HIV
treatment ,bone marrow transplantation, AIDS
or cancer
Toxicity: thrombosis ,cardiovascular events
when used along with some other
erythropoietic agents