AGENTS USED IN

ANEMIAS;
HEMATOPOIETIC
GROWTH FACTORS
 TOPIC OUTLINE

1. Hematopoiesis
2. Erythropoiesis
3. Anemia
• Agents for Anemia
• Iron
• Vitamin B12
• Folic Acid
4. Hematopoietic Growth Factors
 HEMATOPOIESIS
• The formation of blood
• The developmental processes of the
formed elements (erythrocytes,
platelets, and leukocytes) in blood
• in the red bone marrow from the descendants of
the pluripotent hemopoietic stem cell by the
processes of proliferation and differentiation
• each stem cell can give rise to as many as
211 mature cells
 ERYTHROPOIESIS
• The formation of red blood cells
• Starts in the proerythroblast
LIFE CYCLE OF ERYTHROCYTES
REGULATION OF RBC PRODUCTION
 ANEMIA
• A deficiency in oxygen-
carrying erythrocytes
 AGENTS USED IN ANEMIAS
(NUTRITIONAL)

I. IRON
II. VITAMIN B12
III.FOLIC ACID
 IRON FACTS

• The human body contains an average of 3.5 g of

iron (males 4 g, females 3 g)
• Necessary for oxygen transport, energy
production, and cellular growth and proliferation
• 70% of absorbed iron forms the nucleus of iron-porphyrin
heme ring which together with the globin chains forms
hemoglobin
• 10% to 20% of absorbed iron is stored in
ferritin molecules, so it can be recycled
for erythropoiesis
ABSORPTION, TRANSPORT, AND
STORAGE OF IRON
 Iron is bound and
transported in the body
via transferrin and
stored in ferritin
molecules.

Once iron is absorbed,

there is no physiologic
mechanism for
excretion of excess iron
from the body other
than blood loss i.e.,
pregnancy,
menstruation or other
bleeding.
 IRON DEFICIENCY

• Iron deficiency is the most common cause of

chronic anemia
• Iron-deficiency anemia leads to pallor, fatigue,
dizziness, exertional dyspnea and other generalized
sx of tissue hypoxia
• What is the importance of iron?
• Heme formation = important for hemoglobin synthesis
• Less Iron = less heme = less hemoglobin = less oxygen
transport
 IRON DEFICIENCY

• Absence of adequate iron , small erythrocytes with

insufficient hemoglobin are formed, giving rise to
MICROCYTIC HYPOCHROMIC ANEMIA
 PHARMACOLOGY OF IRON

• Iron preparations are clinically indicated for the

treatment or prevention of iron deficiency anemia
• Iron deficiency anemia is treated with oral or
parenteral iron preparations
 ORAL IRON THERAPY

• Ferrous iron is most efficiently absorbed so only

ferrous salts should be used
• Treatment should be continued for 3-6 months after
correction of the cause of the iron loss*
 ADVERSE EFFECTS OF ORAL IRON
THERAPY
• Nausea, epigastric discomfort, abdominal cramps,
constipation and diarrhea
• Usually dose-related
• Patients develop black stools
 PARENTERAL IRON THERAPY

• For patients who are unable to tolerate or absorb

oral iron
• For patients with extensive chronic anemia who
cannot be maintained with oral iron alone
• With advanced chronic renal disease( hemodialysis +
erythropoietin)
• Postgastrectomy conditions and small bowel resection
• IBD involving proximal small bowel
• Malabsorption syndromes
• Iron dextran, Sodium ferrous gluconate complex
and Iron-sucrose complex
 IRON DEXTRAN

• Deep IM injection or by IV infusion

• Disadvantage of Deep IM – local pain and tissue
staining
• Adverse effects of IV iron dextran therapy includes;
• Headache, lightheadedness, fever, athralgias
• N&V, back pain, flushing
• Urticaria, bronchospasm, and rarely, anaphylaxis* and
death
* Small test dose should always be given before full IM or IV
doses are administered
 CLINICAL TOXICITY
ACUTE IRON TOXICITY
• Seen almost exclusively in children who accidentally
ingest iron tablets (10 tabs can be lethal)
• Symptoms include necrotizing gastroenteritis, with
vomiting, abdominal pain and bloody diarrhea
• Shock, lethargy and dyspnea
• Treatment:
• Whole bowel irrigation
• Deferoxamine – a potent iron chelating compound
 CLINICAL TOXICITY
CHRONIC IRON TOXICITY
• Iron overload, also known as hemochromatosis
• Excess iron is deposited in the heart, liver, pancreas, and
other organs
• Can lead to organ failure and death
• Commonly occurs in patients with inherited
hemocromatosis and in patients who receive many
red cell tranfusions over a long period of time (with
thalassemia major)
• Treatment
• Intermittent phlebotomy (in the absence of anemia)
• Deferoxamine (parenteral), Deferasirox (PO) – iron chelators
 VITAMIN B12 (COBALAMIN)

• Used to treat and prevent deficiency

• Megaloblastic, macrocytic anemia
• Neurologic syndromes
• GI symptoms
• Parenteral injections are required for therapy*
• caused by Vitamin B12 deficiency (malabsorption)
 VITAMIN B12 (COBALAMIN)

• Parenteral injections are required for therapy*

• Available as cyanocobalamin or
hydroxocobalamin
• Initial: 100-1000 mcg IM daily or qod for 1-2 weeks to
replenish body stores
• Maintenance: 100-1000 mcg IM once a month for life
 FOLIC ACID

• Reduced forms of folic acid is important for essential

biochemical reactions
• Synthesis of amino acids, purines, and DNA

• Folate deficiency is common

• Consequences:
• Anemia

• Congenital Malformations
 FOLIC ACID

• Treats folate deficiency * such as Megaloblastic

anemia
• Alcohol dependent, liver disease, malabsorption
syndromes, patients on hemodialysis
• Pregnant women and patients with hemolytic anemia –
with high folic acid requirement
• Folic acid 1 mg daily (in almost all patients)
• Sufficient to reverse megaloblastic anemia
• Restore normal serum folate levels
• Replenish body stores of folates
 FOLIC ACID SUPPLEMENTATION

• Should be considered in high-risk patients

• In pregnancy
• Prevention of congenital neural tube defects
HEMATOPOIETIC GROWTH FACTORS

• ERYTHROPOIETIN
• Epoietin alpha, Epoietin beta
• MYELOID GROWTH FACTORS
• G-CSF and GM-CSF
• MEGAKARYOCYTE GROWTH FACTORS
• Thrombopoietin and IL-11