UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes).

Chapter 5

Chapter 5
Polycythemia and Anemia

Intended learning outcomes (ILOs)

By the end of this chapter, the student should be able to
1. Define polycythemia and describe the clinical and pathologic features of each type.
2. Describe the physiological effects of polycythemia.
3. Define anemia.
4. Correlate the factors affecting erythropoiesis to the type of anemia in case of defect in
these factors.
5. Categorize the types of anemia.
6. Differentiate between normocytic, microcytic and macrocytic anemia.
7. Describe the clinical, laboratory and pathologic features of each type of anemia.
8. Define hemoglobinopathies.
9. Define genetic defect in sickle cell anemia.
10. Explain the cause of protection from malaria in sickle cell anemia.
11. Describe the diagnosis of hemoglobinopathies by gel electrophoresis.
12. Define genetic defect in α and -thalassemia.
13. Clarify the compensatory mechanisms in -thalassemia.
14. Identify risk groups for iron deficiency anemia
15. List the different components of anemia control program
16. List the preventive measures for G6PD and Thalassemia
17. Recognize the indications of iron therapy.
18. Compare between oral and parenteral iron therapy.
19. Describe oral iron therapy preparations and adverse effects.
20. Determine the duration of iron therapy.
21. Identify the indications of parenteral iron therapy.
22. Describe parenteral iron preparations and adverse effects.
23. Clarify the advantages of iron total dose infusion.
24. Describe iron toxicity (acute and chronic) and their drug therapy.
25. Describe anemia of chronic inflammatory disease and its treatment.
26. Discuss vitamin B12 therapeutic uses and preparations.
27. Identify the advantages of Hydroxycobalamin over cyanocobalamin.
28. Discuss folic acid therapeutic uses.
29. Describe drug therapy of aplastic anemia.
30. List drug-Induced blood disorders (hemolytic anemia, aplastic anemia, vitamin B12
deficiency anemia, folate deficiency anemia and thrombocytopenia)
31. Enumerate indications of blood transfusion
32. Explain the effect of incompatible blood transfusion
33. Identify precautions before transfusion
34. Mention dangers of blood transfusion

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Polycythemia (Erythrocytosis)
Definition: Polycythemia is the increased number of RBCs in a unit volume of blood
in the presence of increased blood volume.
Effects of polycythemia:
Increase in RBCs number leads to increase in blood viscosity and sluggish blood flow.
Subsequently, increased workload on the heart occurs leading to increased peripheral
resistance which results in high blood pressure.

Types of Polycythemia:
A. Primary polycythemia (Polycythemia rubra vera):
It is considered as a neoplastic disease involving the normoblastic series of the bone
marrow (one of myeloproliferative disorders).
Pathological findings:
1- Cyanosis due to venous engorgement.
2- Enlargement of liver and spleen with foci of extramedullary hematopoiesis.
3- Increased tendency to thrombosis due to the high platelet count and increased
viscosity of blood.
4- Liability to hemorrhages from mucous membranes due to fullness of small
vessels with blood.
5- Peptic ulceration due to thrombosis of gastric small arteries.
6- Chronic myeloid leukemia and myelosclerosis may develop.
B. Secondary polycythemia:
- It is an erythropoietin-induced adaptive mechanism to improve the O2 supply to the
tissue in conditions of prolonged reduction in O2 delivery to the tissues
- The increase in red blood cells is neither accompanied by leucocytosis nor
increased number of platelets.
Causes of secondary polycythemia:
a- Hypoxia: as in high altitudes, cyanotic congenital heart disease and chronic
pulmonary disease.
b- Renal disease: as renal cell carcinoma, congenital polycystic kidney and
hydronephrosis due to secretion of an erythropoietin-like substance.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Anemia
Definition of anemia
• It is a decrease or deficiency of RBCs number or decrease in Hb concentration or
decrease in both RBCs and Hb. in a unit volume of blood in the presence of a low or
normal total blood volume (Fig.2.54).
• It can be caused either by too rapid loss or too slow production of RBCs.

Figure (2.54): The amount of red cells in normal and anemic blood and amount of
oxygen bound to hemoglobin

Classification of anemia can be based on either the cause of anemia or on its type.

Classification of anemia based on its CAUSE

1- Bone marrow hypofunction anemias.
2- Deficiency anemias.
3- Hemolytic anemia.
4- Hemorrhagic anemia.
5- Renal anemia.

I- Bone marrow hypofunction anemias

A- Aplastic anemia: Due to bone marrow aplasia with depression in the formation
of RBCs, white blood cells and platelets (pancytopenia) even though all
ingredients necessary for hemopoiesis are available.
B- Leuco-erythroblastic anemia (myelophthisic anemia):
The bone marrow is replaced by another tissue as metastatic tumors,
myelosclerosis and lipid storage disease.
Causes of aplastic anemia may be:
1) Destruction of the bone marrow due to
a) Excessive X-ray treatment.
b) Certain industrial chemicals and drugs to which the person might be sensitive (as
chloramphenicol, Cytotoxic drugs - chloramphenicol - chlorpromazine – thiouracil).
c) Cancer.
2) Idiopathic (unknown cause that leads the bone marrow to stop functioning).

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

II- Deficiency anemias

It is caused by dietary deficiency of a factor needed for erythropoiesis.

(a) Iron deficiency anemia

It occurs when not enough iron is available for the synthesis of hemoglobin because of
either:
1- Iron deficient diet.
2- Poor iron absorption from digestive tract.
3- Chronic bleeding.
In iron deficiency anemia:
1. The number of erythrocytes produced is normal or reduced.
2. The cells contain less Hb than normal (hypochromic)
3. They are smaller than usual (microcytic) and are able to transport less O2.

Iron deficiency anemia causes hypochromic microcytic anemia .

Pathological findings:
1. Oral manifestations as angular stomatitis (Fig.2.55a).
2. Plummer-Vinson syndrome: occurs in middle aged women with iron deficiency
anemia, glossitis, stomatitis and dysphagia. It usually leads to post-cricoid
carcinoma.
3. Finger nails: Spoon shaped, brittle and lusterless (Fig.2.55 b&c).
4. Bone marrow hyperplasia.
5. Splenomegaly.

a b c

Figure 2.55: (a) Angular stomatitis (b) Spoon nails (c) Brittle lusterless nail
(b) Vitamin B12 or Folic acid deficiency
Deficiency of either vitamin b12 or folic acid or both causes megaloblastic anemia
(maturation failure anemia).
- Because these vitamins are essential for the formation of DNA, their deficiency
leads to diminished and abnormal DNA and thus failure of nuclear maturation
and cell division, with slow reproduction of the erythroblasts in the bone marrow.
- The erythroblasts in the bone marrow will fail to proliferate rapidly and will
produce RBCs larger than normal called macrocytes or megalocytes.
- They cannot proliferate enough to form normal number of red blood cells.
- These cells when enter the circulation are capable of carrying oxygen normally,
but they are fragile and so have a short life.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

1. The number of the newly formed cells is markedly reduced.

2. The cells are mostly oversized of bizarre shapes i.e. macrocytes showing,
Anisocytosis (variable size of the RBCs) and Poikilocytosis (variable shape of the
RBCs).
3. These cells are fragile and thus they rupture easily.

- N.B. Vitamin B12 is also needed for myelin formation, so its deficiency is accompanied
by neurological symptoms. It is also called pernicious anemia.

Pernicious anemia or Addison's anemia:

❑ It is a type of vitamin B12 deficiency anemia.
❑ With a familial tendency, common in subjects of blood group A.
❑ It is due to inability to absorb adequate amounts of vitamin B 12 from the digestive
tract (and not due to insufficient dietary supplies of vitamin B12). This could be due
to:
1- Genetic failure of gastric mucosal cells to produce the intrinsic factor.
2- An autoimmune disease where antibodies cause mucosal atrophy.
❑ Treatment: Injections of vitamin B12 to bypass the defective absorptive
mechanism.

Pathological findings:
1. Hemosiderosis in parenchymatous organs due to continued absorption of iron which
is not adequately used for erythropoiesis.
2. Subacute combined degeneration of the spinal cord (B12 deficiency).
3. Evidence of increased hematopoiesis:
a. Extramedullary foci of hematopoiesis in liver and spleen.
b. Moderate splenomegaly (pernicious anemia).
N.B. Neurological changes do not occur in patients with folic acid deficiency.

III- Hemolytic anemia

It is caused by rupture of excessive numbers of circulating erythrocytes i.e. excessive
hemolysis). As a result, there is reduction in the RBCs count and in the blood Hb level
with rise in serum bilirubin leading to jaundice.
A- Intracorpuscular defect (Hereditary):
1. Hereditary spherocytosis:
Carried as an autosomal dominant gene. There is a defect in RBCs membrane
with formation of nondeformable spherocytes highly vulnerable to destruction in
the spleen.
2. Haemoglobinopathies (Abnormal hemoglobin):
a- Sickle cell disease: Sickling occurs due to the insolubility of Hb-S and occurs
when oxygen tension is reduced.
b- Thalassemia This occurs in Mediterraneans. The production of α or B-chains

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

of globin is impaired
3. Enzyme-deficient RBCs:
➢ Due to glucose-6-phosphate dehydrogenase deficiency in RBCs.
➢ The RBCs are susceptible to hemolysis after administration of certain drugs as
primaquine, sulphonamides, phenacetin and aspirin or ingestion of fava beans
(vicia faba) leading to favism.
B- Extracorpuscular defects (Acquired):
1. Auto Antibodies: As chronic lymphocytic leukemia, systemic lupus
erythematosus.
2. Iso-antibodies: Erythroblastosis fetalis.
3. Poisons: as snake venom or certain drugs if given in large amount as
phenylhydrazine, arsenic and lead.
4. Incompatible blood transfusion.
Pathological findings of hemolytic anemias:
1. Bone marrow hyperplasia.
2. Extramedullary hematopoiesis.
3. Splenomegaly.
4. Hemosiderosis.
5. Gall bladder stones.

IV- Hemorrhagic anemia

It is caused by excessive blood loss, which can be:
1- Acute e.g. bleeding from a wound.
2- Chronic e.g. excessive menstrual flow or bleeding piles.

V- Renal anemia
In which inadequate secretion of erythropoietin hormone (as a result of kidney disease)
causes insufficient red blood cell production and anemia.

Classification of anemia based on appearance of cells

I- Normocytic normochromic anemia: RBCs are normal in size and Hb content per
cell is normal e.g. aplastic anemia and hemorrhagic anemia.
II- Microcytic hypochromic anemia: RBCs are smaller in size and Hb is decreased
in amount in each cell e.g. iron deficiency anemia.
III- Macrocytic anemia: RBCs are larger in size and e.g. megaloblastic anemia.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Microcytic hypochromic anemia Megaloblastic anemia

Erythroblastosis fetalis Sickle cell anemia

Figure (2.56): Different types of anemia

General pathological effects of anemia:

1. Those due to hypoxia.
2. Increased cardiac output to meet the oxygen demands of the tissues, eventually
leading to heart failure.
3. Pallor of skin and mucous membranes.
4. Fatty change in parenchymatous organs.

Hemoglobinopathies and Hb Electrophoresis

Hemoglobinopathies are defined as a group of genetic disorders caused by production
of a structurally abnormal hemoglobin molecule; synthesis of insufficient quantities of
normal hemoglobin; or rarely both.

Mutations in α- or β-globin genes can cause disease state as sickle cell anemia
and thalassemia.
1. Sickle cell anemia:
• Sickle cell anemia is an autosomal recessive disease in which a mutation occurs
in β-chain: E6 (polar negatively charged glutamic acid) is changed to V6
(hydrophobic valine).
• Valine as a hydrophobic amino acid will bind to hydrophobic pocket in deoxy-Hb
• This type of hemoglobin is called hemoglobin S (HbS).
• HbS polymerizes to form long filaments when oxygen tension is reduced
• It causes sickling of RBCs.
• Such sickled cells frequently block the flow of blood in the narrow capillaries. This
leads to localized anoxia (oxygen deprivation) in the tissue, causing pain and
eventually death (infarction) of cells in the vicinity of the blockage.
• Sickle cell anemia offers advantage against malaria.
• Fragile sickle cells cannot support parasite.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Normal Trait Anemia -

Hb S

Hb A

+
Figure (2.57): Diagnosis of sickle cell anemia by gel electrophoresis

2. Thalassemias
• The thalassemias are hereditary hemolytic diseases in which an imbalance
occurs in the synthesis of globin chain “decreased rate of synthesis of globin
chains”.
• -Thalassemias:
➢ Decreased rate of synthesis of -globin chains.
➢ Each individual ‘s genome contains four copies of the  globin gene(two on
each chromosome 16), there are several levels of the disease state that
originate from deletion mutation of these gene copies.
➢ The deletion of the 4 genes is incompatible with life. Deletion of three copies
will result in only ¼ of the hemoglobin molecules to be efficient in oxygen
transport, the so-called hemoglobin H disease. It is severe condition of
hemolytic anemia demanding life-long blood transfusions.
➢ Deletion of two copies, this will be an  thalassemia trait, in which the person
may be asymptomatic, however his offspring may develop more severe
disease if another affected gene came from the other parent.
➢ Deletion of only one copy of the four  genes will result in a silent carrier state.
• -Thalassemias:
➢ Decreased rate of synthesis of -globin chains. The  or  chains will increase.
➢ Increase in α2δ2 (HbA2) and α2γ2 (HbF) occurs.
➢ There are only two copies of the β-globin gene in each cell, therefore,
individuals with β-globin gene defects have either β-thalassemia trait (β-
thalassemia minor) if they have only one defective β-globin gene or β-
thalassemia major (Cooley anemia) if both genes are defective.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

➢ Infants born with β-thalassemia major become severely anemic, usually

during the first or second year of life due to ineffective erythropoiesis. Skeletal
changes as a result of extramedullary hematopoiesis are also seen. These
patients require regular blood transfusion.
Other types of hemoglobinopathies
• Hb M: Substitution of proximal histidine by tyrosine causing oxidation of Fe 2+ to Fe3+
forming methemoglobin.
• Hb C: Substitution of two glutamate residues in the -chain by lysine casing mild
hemolytic anemia.

Epidemiology and Prevention of Selected Anemias

1- Iron Deficiency Anemia (Ida)

Risk Groups and prevalence of iron deficiency anemia:

o Infants and Preschool children: According to UNICEF (2104), prevalence of IDA
among 6-59 months old Children is 27% IDA and more Prevalent in Rural Areas.
o Adolescents.
o Woman of child-bearing age particularly pregnant and lactating women: According to
the Egyptian DHS (2005), the prevalence of anemia was 39.4% for ever-married
women (age 15 to 49 years).
▪ Anemia has been associated with many problems for women and children, it
increases the risk of maternal deaths, low birth weight and peri-natal mortality.
▪ Interventions correcting anemia should be offered to all women even before the first
pregnancy as the hemoglobin drops physiologically with pregnancy.
▪ Anemia in Pregnancy: The early stages of anemia in pregnancy are often without
symptoms. However, as the hemoglobin concentration falls, oxygen supply to vital
organs declines, and the expectant mother begins to complain. Anemic mothers do
not tolerate blood loss to the same extent as healthy women (beware of postpartum
hemorrhage).
▪ Junk food: may be related to iron deficiency anemia as it contains less iron and
causes obesity. Obesity increases Hepcidin Levels. Hepcidin is a small, cysteine-rich
cationic peptide produced by hepatocytes, secreted into plasma, and excreted in
urine. Hepcidin expression is induced by iron stores and inflammation and is
suppressed by hypoxia and anemia. High Hepcidin Levels lower Iron Levels.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Anemia Control Program

It is an organized plan for prevention and control of anemia. Anemia control through
Primary Healthcare (PHC) should be considered as an integrated method of total
health care. It is implemented through Primary Health Care units tackling 4 different
approaches.

1- Supplementation:
Giving medical iron has the advantage of producing rapid improvements in iron status.
The success of supplementation depends on a well-organized (PHC) system through:

a. Adequate population coverage of target groups e.g. reaching pregnant and

lactating females in MCH centers, school children through school health services.
b. Effective education and motivation of recipients (target groups) to ensure their
continuous taking of treatment.
c. Training of health personnel of the needed dosage for each group, follow up,
management of any effects, and regular supply of supplements.

2- Dietary modification:
It consists of 2 basic parts:
a. Correct the under nutritional status: as when energy needs are fully met, the total
iron consumption is increased. This is a simple approach especially in rural areas.
b. Quality of iron ingested and absorbed should be improved:
- Increase ascorbic acid content of diet (eating fruits and vegetables).
- Reduce ingestion of inhibitors of absorption.
- In weaning, foods prepared should be rich in Vitamin C and iron.
- Importance of breast milk for infant (iron in breast milk is highly absorbable).

3- Infection control:
a. Control of viral, bacterial and parasitic infections contributes to the iron status
even if there is no increase in dietary iron consumption.
b. Provision of safe water and environmental sanitation will decrease diarrheal
diseases which affects iron absorption.
c. Treatment of parasitic infestations e.g. ancylostomiasis, necator, giardia.
d. Sick children should be properly fed (change the wrong believes of rural families
where they avoid proper nutrition to sick children: semi-starvation state).

4- Fortification
Definition: addition of one or more nutrient to any food to improve the
quality of the diet of a group or community.
In anemia, wheat flour, salt, sugar, milk and milk products and rice can be
fortified with iron.
In cases of severe anemia (Hb. Conc. < 7g /dl) cases should be referred to a
district hospital (Intermediate level of health care) to receive advanced treatment.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

2- G6PD Deficiency

Prevalence & risk factors

• The prevalence of G6PD among Egyptian children is 1 %.
• Risk factors
- Consanguinity plays a major role in the incidence of this disease.
- It affects males more than females.
- Exposures that lead to hemolytic attacks are: fava beans and certain drugs
(oxidizing agents) such as: Antipyretics (Aspirin), Anti-malarial drugs,
Sulfonamides, Chloramphenicol, and Naphthalene.

• Prevalence of types of G6PD:

1. Type A: common in American blacks. The enzymatic activity is 5-15% of the
normal and leads to less severe hemolytic attacks.

2. Type B: common in Mediterranean area. The enzymatic activity is less than

5% of normal and leads to severe hemolytic attacks and death may occur in
severe cases.

Prevention:
1. Early diagnosis (Genetic counseling and screening may be of value for positive
family history).
2. Health education of the parents of children with G6PD disease for
prohibiting the previous drugs that causes hemolysis.
3. Epidemiologic surveillance

3- Thalassemia
The most common type is Beta thalassemia (Mediterranean Sea anemia). Alpha
thalassemia is common in Asia.

Epidemiology and risk factors of Beta thalassemia

It is a major health problem in Egypt and is of high incidence in the Arab countries in
general. It is the most common cause of chronic hemolytic anemia in children
commonly present after the 6th month of age. It has been estimated that from each
1.5 million live births, around 1000 children are born with beta thalassemia annually.
Risk Factors: consanguineous marriage.

Prevention
1. Premarital counseling, genetic counseling, neonatal screening and screening for
carrier.
2. Health education about the hazards of consanguinity.
3. Tertiary prevention: Rehabilitation programs.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Drug Therapy of Iron-Deficiency Anemia

(Microcytic Hypochromic Anemia)
IRON
Indications of Iron Therapy:
1. Prophylactic, to prevent development of iron-deficiency anemia (IDA):
30-60 mg/day elemental iron1.
2. Treatment of IDA: 200-400 mg/d elemental iron 2 . Ferrous salts
are usually
Iron Therapy (Oral - IV - IM)
used as
I. Oral Iron Therapy:
ferrous iron
• Effective & cheap (treatment of choice).
is efficiently
• Oral preparations include ferrous sulfate, gluconate
and fumarate. absorbed.
• Different Fe salts provide different amounts of elemental Fe (range from 12-33%).
• New agents: polysaccharide-iron complex 150 mg, carbonyl iron 150 mg contain
100% elemental iron.
• Heme iron polypeptide: More expensive than above agents.
• Given after meals to decrease GIT disturbances (carry risk of decrease absorbed
portion).
• Continue iron till Hb is normal & for an extra 2-3 months to replenish stores3.
Adverse Effects of Oral Iron Therapy:
1. GIT disturbances: nausea, epigastric pain, constipation (given after meals - start
with small dose then gradually increase).
2. Black stools (mask diagnosis of GI bleeding).
3. Black staining of teeth (iron sulfide in mouth).

II. Parenteral Iron Therapy:

Indications (= Causes of failure of oral iron therapy)
1. Noncompliance to oral therapy (severe GIT disturbance or ulceration).
2. Malabsorption syndrome causes failure of iron absorption.
3. Severe anemia, e.g. in malignancy.

1
Elemental iron is the total amount of iron in the supplement available for absorption.
2
In Fe deficient individuals, about 50-100 mg of Fe can be incorporated into hemoglobin daily, and about
25% of oral Fe given can be absorbed. Therefore, 200-400 mg of elemental iron should be given daily.
3
It takes from 7-10 days to increase hemoglobin level by 1g/dl

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Calculation of Parenteral Iron

(There are many formulae to determine parenteral iron required to
correct anemia & replenish stores).
e.g.
Total iron deficit (mg) = Body weight [kg] x (Target Hb – Actual
Hb) [g/l] x 2.4 + 500 [mg] (for iron stores)

Parenteral Iron Preparations:

A. Iron dextran.
B. Iron sucrose complex & Iron sodium gluconate complex.
C. Newer preparations: Ferric carboxymaltose, Ferumoxytol4 Given by deep IMI or
by IV infusion (as a total dose infusion, TDI).
Advantages of TDI:
1) Avoids non-compliance of the patient.
2) Avoids unpleasant effects of IMI.
3) Allows delivery of the entire dose of iron necessary to correct iron deficiency at
one time.
Adverse Reactions of parenteral iron therapy:
• IM: local pain - tissue staining.
• IV: headache, fever, urticaria, lymphadenopathy & anaphylactic shock (with Fe
dextran, start with a small test dose).
N.B. Iron sucrose complex, Iron sodium gluconate complex, Ferric carboxymaltose,
Ferumoxytol are less likely to cause hypersensitivity.

Iron Toxicity
➢ Acute Iron Toxicity (more in children)
Abdominal pain, vomiting, bloody diarrhea, dyspnea followed by metabolic acidosis,
cardiovascular collapse, convulsions, coma & death.
Treatment (urgent and immediate)
1. Raw egg or milk  bind & precipitate iron as albuminate or caseinate until a
chelating agent is available.
2. Deferoxamine:
• 1-2 g IM or IV  chelates iron promoting its excretion in urine.
• 5 g in 100 ml water swallowed or by stomach tube (after gastric lavage with
bicarbonate solution5.
3. IV infusion of saline, dextrose or bicarbonate  correct water & electrolyte
disturbance.

4
Superparamagnetic iron oxide nanoparticles coated - interfere with MRI.
5
Bicarbonate forms insoluble iron salts.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

➢ Chronic Iron Toxicity

It occurs in:
1. Patients receiving many red cell transfusions.
2. Patients with hemochromatosis; an inherited disorder characterized by increased
Fe absorption  hemosiderosis (Fe3+ precipitation in vital organs).
Management
1. Venesection 6 (if no anemia)  repeated weekly.
2. iron chelators:
• Deferoxamine: IM or SC.
• Deferasirox: a new oral iron chelator.
3. Large intake of tea  tannins bind iron.

Anemia of chronic disease

o It is a functional iron deficiency anemia.

o Occurs when there is infection and inflammation with release of cytokines that
stimulate the release of hepcidin from the liver.
o High levels of hepcidin prevent absorption & release of iron from its storage sites
(sequestrated anemia).
o To be differentiated from iron deficiency anemia, there is normal or high serum
ferritin.
o Not treated with iron but its treatment is to treat infection & inflammation.

6
A single venesection of 500 ml blood removes 200 mg iron.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Treatment of Agranulocytosis or Aplastic Anemia

1. Eliminate the underlying cause (e.g. stop drugs, avoid chemical exposure).
2. Supportive treatment:
- Prevent and treat infection (broad-spectrum antibiotics).
- Prevent and treat hemorrhage.
- Treat anemia (blood transfusion if patient hg 7-9 g/dl).
- Replace lacking blood components.
3. Corticosteroids: reduce bleeding due to thrombocytopenia.
4. Bone marrow transplantation (treatment of choice) preceded and followed by
immunosuppression with cyclosporin to prevent graft rejection.
5. Intravenous antithymocyte immunoglobulin.
6. Anabolic agents (not in severe cases).
6. Erythropoietin.
Erythropoietin (IV or SC) 7
1. Regulator of erythropoiesis (acts on stem cells).
2. Used in anemia of chronic renal failure & severe anemia of cancer & AIDS.
3. It decreases the need for transfusion as it elevates red blood cell level.
4. Common complications include hypertension and thrombosis.

Drug Therapy of Megaloblastic Anemia

(Vitamin B12 and Folic Acid Deficiency)
I. Vitamin B12
Preparations of Vitamin B12
A. Cyanocobalamin
B. Hydroxycobalamin (preparation of choice):
1. More slowly absorbed.
2. More bound to plasma proteins.
3. Slowly excreted.
4. More sustained rise in serum cobalamin.

Therapeutic uses of Vitamin B12

A. Megaloblastic Anemia
1. Pernicious anemia: vitamin B12 is given for life by IMI.
• Initial therapy: 1,000 g/day for 1-2 week to replenish stores. Then 1,000
g/week till normal blood count.
• Maintenance therapy: 1,000 g/month for life.
2. Megaloblastic anemia due to diphylobothriasis:
• It is treated by vitamin B12 and praziquantel.

7
Types of recombinenet human erythropoeitin include: Epoietin alpha, Epoeitin beta (1-3 times/ week), Darbepoetin
alpha (every 1-2 weeks), Methoxy polyethylene glycol-epoeitin beta (every 2 weeks-1 month).

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

3. Drug-induced megaloblastic anemia:

• Neomycin, colchicine and antiepileptics reduce absorption of B12.
B. Neurological Conditions
• Peripheral neuritis in diabetes & retrobulbar neuritis in heavy smokers.

II. Folic Acid (Pteroylglutamic Acid)

Therapeutic uses of folic Acid

1. Nutritional megaloblastic anemia.
2. Malabsorption syndrome.
3. In alcoholics and pregnant women.
4. Patients with liver disease & with hemolytic anemia.
5. With anticonvulsant drugs.
6. Patients on dialysis (as folic acid is removed each time).

Drug-Induced Blood Disorders

A. Hemolytic Anemia (destruction of RBCs)
1. In G6PD-deficient subjects
1. Antimalarial drugs.
2. Aspirin.
3. Sulfonamides.
4. Quinine and quinidine.
2. As a Hypersensitivity Reaction
1. Penicillin 2. Sulfonamides.
3. Autoimmune Hemolytic Anemia : methyldopa.
B. Thrombocytopenia
• Heparin - rifampin - indomethacin - quinine - quinidine.
• Treatment: stop the drug - platelet transfusion - corticosteroids.

C. Bone Marrow Depression (aplastic Anemia or agranulocytosis)”

Cytotoxic drugs - chloramphenicol - chlorpromazine - thiouracil.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

Blood Transfusion
It is the process of transferring blood or blood products from one person into the
circulatory system of another.
Indications:
1. Hemorrhage: from severe trauma or after surgical operation (to restore blood
volume) and bleeding attacks due to disturbances in clotting mechanisms or platelet
function (transfusion of clotting factors).
2. Severe anemia: (to restore Hb level), people suffering from hemophilia or sickle-cell
disease may require frequent blood transfusions.
3. Erythroblastosis fetalis.

Figure (2.58): Blood transfusion

Transfusion reactions: (Effects of incompatible blood transfusion)

• Hemolytic transfusion reactions occur when blood is transfused to an individual with
incompatible blood group i.e. when the recipient has agglutinins against the RBCs in
the donor’s blood.
• The transfused plasma (donor's plasma) is usually so diluted in the recipient that it
rarely causes agglutination.
• When recipient’s plasma has agglutinins against the donor's red cells, the cells
agglutinate and hence:
1. Agglutinated RBCs form clumps which block capillaries leading to pain and
tightness of the chest immediately. The clumps are then hemolyzed, releasing Hb
into plasma causing jaundice.
2. The cells hemolyze. Free Hb is liberated into the plasma. The severity of the
transfusion reaction may vary from minor asymptomatic rise in plasma bilirubin to
severe jaundice (hemolytic jaundice), renal tubular damage and renal failure
and may be death.
3. Histamine release from the hemolyzed RBCs causing vasodilatation and
resulting in hypotension.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

4. Acute kidney shutdown:

There are three causes:
a- The antigen-antibodies reaction of the transfusion reaction releases toxic
substances from the hemolyzing RBCs and causes powerful renal
vasoconstriction with reduction in the glomerular filtration rate.
b- Circulatory shock from the loss of RBCs and the production of toxic
substances decreasing the glomerular blood flow and urine output.
c- Renal tubular blockage due to Precipitation of Hb which passes through the
glomeruli by the acidic urine in the form of acid hematin which obstruct the
lumen of the tubules decreasing the flow of urine.
o Thus, renal vasoconstriction, circulatory shock, and renal tubular blockage
together cause acute renal shutdown.
o Due to renal failure there is uremia and hyperkalemia.
o If the shutdown is complete and fails to resolve, the patient dies within a
week to 12 days.

Precautions before blood transfusion:

1- Blood typing: the donor's blood should be compatible with that of the recipient
regarding ABO system and Rh factor.
2- Cross matching test: should be done "The donor's cells are added to the
recipient plasma and the donor's plasma tested with the recipient cells". This test
is done to avoid incompatibility due to any subgroup, or due to increased
concentration of agglutinins in the donor's plasma.
3- A healthy donor must be carefully chosen with no history of serious diseases
such as: Hepatitis, HIV (human immunodeficiency virus) or AIDS, Malaria and
Syphilis.
4- Good storage of the blood with the addition of acid citrate (to prevent its clotting)
and glucose (as a nutrient to the RBCs). The blood should be kept at a
temperature of 4º C in the blood banks and not frozen, otherwise the RBCs will
be destroyed. The blood should not be used after 5 weeks.

Dangers of Blood Transfusion:

1- Immediate:
1. Acute hemolytic (Incompatibility) reactions as fever, chills, pain, dyspnea,
hypotension, jaundice, dark urine (that reflects hemoglobinuria) and acute renal
failure.
2. Febrile Non-Hemolytic Reactions: Fever is body’s response to the white blood cells
in the transfused blood (white cell antibodies in a recipient react with white blood
cells in a transfused blood).
3. Allergic Reactions: i.e. urticarial, itching. They arise from recipient antibody
response to donor plasma proteins. They arise from recipient antibody response to
donor plasma proteins.
4. Mechanical overloading of the circulation particularly in patients with cardiac
diseases.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

5. Hyperkalemia: With storage there is increased amount of K+ in the plasma due to

its release from old hemolyzed cells that may lead to ventricular fibrillation and
sudden death.
6. Transfusion-related acute lung injury (TRALI) characterized by acute respiratory
distress and pulmonary edema with hypoxaemia
7. Citrate intoxication with massive transfusion due to excessive citrate infusion: this
may produce decreased ionized calcium (hypocalcemia) and magnesium
(hypomagnesaemia) as citrate binds calcium and magnesium and acidosis.
8. Bacterial infection: due to contamination of blood by bacteria specially with cold-
growing gram-negative bacilli. After a latent period, it produces shock associated
with fever.

N.B. Prolonged storage at room temperature (more than 4 hours) encourages the
growth of contaminating bacteria.

II- Delayed:
1. Transmission of diseases e.g. AIDs, hepatitis, malaria and syphilis.
2. Iron overload: Most common in patients that receive repeated transfusions due to
too much iron from donor blood. This can produce damage to organs as liver
(developing liver cirrhosis), pancreas (diabetes mellitus) and heart (cardiotoxicity
which causes arrhythmias and congestive heart failure), joints (arthralgia) and skin
(hyperpigmentation).

Massive blood transfusion

Definition:
It replacement of 50% of total blood volume within 3 hours or transfusion of a volume of
blood greater than or equal to one blood volume in 24 hours ((eg, 10 units in a 70-kg
adult)

Complication:
1. Circulatory overload especially in cardiac patients
2. Hypothermia because bloods is stored at 4OC
3. Hyperkalemia because stored blood release potassium
4. Dilutional coagulopathy of clotting factors and platelets (thrombocytopenia) leading to
bleeding
5. Citrate toxicity
6. Transfusion-related acute lung injury (TRALI)

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

➢ Polycythemia: primary and secondary.

➢ Anemias are classified according to cause into: aplastic anemia, deficiency anemia,
hemolytic anemia, hemorrhagic anemia and renal anemia.
➢ Anemias are classified according to microscopic appearance into: normocytic
normochromic anemia, microcytic hypochromic, and macrocytic hyperchromic.

➢ Deficiency anemia are: Iron deficiency anemia, megaloblastic anemia.

➢ Hemolytic anemias are: 1- intracorpuscular: spherocytosis, haemoglobinopathies
and enzyme deficient RBCs. 2- extracorpuscular: autoantibodies (Hodgkin, systemic
lupus) or isoantibodies as in erythroblastosis fetalis. 3- infective agents. 4- poisons.
➢ Bone marrow hypofunction anemias: Aplastic anemia and leucoerythroblastic.

➢ Iron deficiency anemia represents one of the most common nutritional related health
problems in Egypt especially to females all through childbearing age groups.
➢ Other blood diseases common in Egypt include G6PD and Beta thalassemia.
➢ Premarital counseling and screening for thalassemia are important aspects for
prevention of such important and disabling disease.
➢ Hemoglobinopathies are defined as a group of genetic disorders caused by
production of a structurally abnormal hemoglobin molecule; synthesis of insufficient
quantities of normal hemoglobin; or, rarely, both.
➢ Mutations in α- or β- globin genes can cause disease state as sickle cell anemia and
thalassemia.
➢ Sickle cell anemia results from substitution of glutamate by valine at position 6 in the
β- globin chain.
➢ The α- and β- thalassemias are anemias that result from reduced production of α-
and β- subunits of HbA, respectively.
➢ Other types of hemoglobinopathies include:
– Hb M (methemoglobinemia)
– Hb C (mild hemolytic anemia).

➢ Iron therapy is used either for prevention or treatment of iron deficiency anemia.
➢ Oral iron therapy is effective & cheap (treatment of choice).
➢ Ferrous salts are usually used as ferrous iron is efficiently absorbed.
➢ Continue iron till Hb is normal & for an extra 2-3 months to replenish stores.
➢ Parenteral iron therapy is indicated in severe anemia and failure of oral iron therapy.
➢ TDI Allows delivery of the entire dose of iron necessary to correct iron deficiency at
one time by Intravenous infusion.
➢ Acute Iron Toxicity requires urgent treatment with raw egg or milk, IV fluids and
Desferrioxamine.

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UNIT II: Red Blood Corpuscles (RBCs) (Erythrocytes). Chapter 5

➢ Anemia of chronic disease is a functional iron deficiency anemia occurring with

inflammatory conditions with due to release from the liver.
➢ Anemia of chronic disease is not treated with iron, but its treatment is to treat infection
& inflammation.
➢ Erythropoietin is used in anemia of chronic renal failure & severe anemia of cancer
& AIDS.
➢ Vitamin B12 is used for treatment of megaloblastic anemia, peripheral neuritis (in
diabetes) and retrobulbar neuritis (in heavy smokers).
➢ Hydroxycobalamin is the vitamin B12 preparation of choice.

➢ Blood transfusion is indicated in hemorrhage, severe anemia and erythroblastosis

fetalis
➢ Incompatible blood transfusion:
o Agglutinated RBCS clump and block capillaries leading to pain
o Hemolysis leading to release of free Hb, jaundice, histamine release and hypotensive
shock and renal failure
➢ Precautions before blood transfusion: do blood typing, cross matching test, choose
healthy donor and good storage.
➢ Dangers of blood transfusion: Immediate: Acute hemolysis, febrile reactions, allergic
reactions, mechanical overload, hyperkalemia, citrate toxicity- Delayed: Blood
transmitted diseases as AIDS, iron overload

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