The document discusses vitamin B12 deficiency anemia. It defines anemia and describes the stages and pathophysiology of vitamin B12 deficiency. Key points include: - Vitamin B12 deficiency can result from inadequate intake, malabsorption, or inadequate utilization. The major causes are pernicious anemia resulting from gastric acid and intrinsic factor deficiencies impairing vitamin B12 absorption. - There are three stages of vitamin B12 deficiency: stores depletion, impaired erythropoiesis, and anemia with neurological symptoms potentially developing at severe deficiency. - Vitamin B12 works with folate in DNA/RNA synthesis and its absorption requires intrinsic factor to form a complex for distal ileum absorption. G

1. Sohan Patel,
Assistant Professor,
Dept. of Pharmacology,
Modasa, Gujarat, India

2. DEFINITION
Anemia's are a group of diseases characterized
by a decrease in either the hemoglobin (Hgb)
or the volume of red blood cells (RBC’s) in
blood.
Results in decreased oxygen-carrying
capacity of the blood.

3.  WHO define Anemia in adult as hemoglobin levels
less than 13g/dl in males, less than 12g/dl in
females and less than 13g/dl in pediatrics.

4. Anemia can result from :
1) Inadequate RBC production.
2) Accelerated loss of RBC mass.
3) host of systemic disorders such as infection, chronic
renal diseases or malignancy.

5. MATURATION AND DEVELOPMENT
OF RBC

6. ETIOLOGY
 Etiology basically consist of three mechanism:
1) Reduced Hemoglobin synthesis which may be due to lack
of nutrients or bone marrow failure. This leads to either reduced
proliferation of precursors or defective maturation of precursors or both.
2) Increased hemoglobin loss due to hemorrhage (red cell
loss) or heamolysis (red cell destruction)
3) Decreased red cell production i.e. disturbance in stem cell
proliferation or differentiation.

7. Classification :-
Anemias can be classified on the basis of
1. Morphology of the RBCs,
2. Etiology, or
3. Pathophysiology.

8. 1. Morphological Class
Anemias are classified by RBC size as
Macrocytic Anemias
Megaloblastic anemias
 Vitamin B12 deficiency anemia
 Folic acid deficiency anemia
Microcytic, hypochromic anemias
Iron deficiency anemia
Genetic anomaly
 Sickle cell anemia
 Thalassemia
 Other hemoglobinopathies (abnormal hemoglobins)

9. Normocytic anemias
Recent blood loss
Hemolysis
Bone marrow failure
Anemia of chronic disease
Renal failure
Endocrine disorders
Myeloplastic anemias

11. Deficiency
Iron
Vitamin B12
Folic acid
Pyridoxine
impaired bone marrow function
Anemia of chronic disease
Anemia of the elderly
Malignant bone marrow disorders
Peripheral
Bleeding (hemorrhage)
Hemolysis (hemolytic anemias)
Etiology Class

12. Pathophysiology Class
Excessive blood loss
Recent hemorrhage
Trauma
Peptic ulcer
Gastritis
Hemorrhoids

13. • Chronic hemorrhage
– Vaginal bleeding
– Peptic ulcer
– Intestinal parasites
– Aspirin and other NSAIDs
• Excessive RBC destruction
• Inadequate production of mature RBCs

15. Iron deficiency Anemia (IDA)
Iron deficiency is the most common nutritional
deficiency in developing and developed countries and it
is estimated that over 500 million people worldwide
have IDA*
Hemoglobin consist of protein component with 2 alpha
and 2 beta chains.
*Data from the Third NHANES (National Health and Nutrition Examination Survey)

16. Each chain linked to a heme group consisting of a
porphyrin ring structure with an iron atom chelated at
its center which is capable of binding oxygen.
Iron stores are 600-1200 mg for males and 100-400
mg for females, only 0.5-1.0 mg/day is lost ; another
0.5-1.0 mg is lost daily during menstruation.
Daily requirement of Iron 0.9mg in males, 2mg
females, in pregnancy it is 3-5mg and in infant it is
0.5mg.

17. Etiology of IDA
 Iron deficiency results from prolonged
negative iron balance.
 The speed of iron deficiency development
depends on an individuals initial iron stores
and balance between iron absorption and
loss.

18.  Multiple etiologic factors are usually involved.
1) Blood loss (Menstruation, Gastrointestinal peptic
ulcer, Trauma)
2) Decreased absorption due to medication (e.g..
Drugs like Tetracycline) or Gastrectomy or regional
enteritis.
3) Increased requirement (Infancy, Pregnancy or
lactating females)
4) Impaired utilization (Heredity, decreased iron use)

19. Pathophysiology of IDA
Diminished total body iron content, developing in stages
over a period of negative iron balance
Iron depletion – Stage One
Iron deficient erthyropoiesis – Stage Two
Iron deficiency anemia – Stage Three
Stage One
Iron storage is exhausted - indicated by decrease in serum ferritin
levels No anemia – RBC morphology is normal.

20. Stage Two
Insufficient iron to insert into protoporphyrin ring to form heme
– Protoporphyrin accumulates in cell and complexes with zinc
to form ZPP No anemia, no hypochromia, but slight
microcytosis may be decreased
Stage Three
All laboratory tests for iron status become abnormal, Most
significant finding is microcytic, hypochromic anemia and there is
hyperplasia of erythroids.

21. Signs of IDA
1) Pale skin and mucous membrane
2) Painless glossitis (Inflammation of the tongue)
3) Angular stomatitis (Inflammation of the mucous membrane
of the mouth)
4) Koilonchia (Spoon shaped nails)
5) Dysphagia
6) Pica (Unusual cravings)
7) Atrophic Gastritis
8) Poikilocytes (misshapen red cells appear on the blood smear
as cigar-or pencil-shaped forms)
Chronic Iron
deficiency

22.  Symptoms
1) Faintness
2) Fatigue
3) Dizziness
4) Irritability
5) Malaise
6) Palpitation
7) Headache
8) Shortness of breath
9) Angina
10) Ankle edema

23. Treatment of IDA
replenish iron stores.
dietary supplements and administration of therapeutic iron
preparation. It is best absorbed from meat, fish and poultry.
Beverages affect iron absorption.
In most cases oral administration of iron therapy with soluble
iron salts is appropriate.
ORAL THERAPY
Iron sulphate, succinate, lactate, fumarate, glycine sulphate,
glutamate and gluconate are absorbed
The presence of mucopolyssacharides chelator substance
prevents the iron from precipitating and maintains the iron in
soluble form.

24.  The dose of iron replacement therapy depends on the
patients ability to tolerate the administered iron.
 The general recommendation is approximately administered
of 200mg of elemental iron daily normally in 2 to 3 divided
doses to minimize tolerability.
 If patient cannot tolerate this than smaller amount of
elemental iron e.g. single 325mg tablet of iron sulphate is
sufficient.
 Iron is preferably administered at least 1 hour before meal to
avoid food-drug interaction.
 Many patient may take iron with food because they
experience nausea and diarrhea when administered on empty
stomach.

26. Adverse Drug Reaction (ADR)
ADR to therapeutic dose of iron are Gastrointestinal in nature
1) Discoloration of feaces
2) Constipation and diarrhea
3) Nausea and vomiting
Drug Interaction
 Drugs which decrease iron absorption
1) Aluminum, magnesium and calcium containing antacids
2) Tetracycline and doxycycline
3) Histamine (H2) antagonist
4) Proton pump inhibitor
5) Cholestyramine

28. Drugs affected by Iron
1) Levodopa ↓ (chelates with iron)
2) Methyldopa ↓ (decreases efficacy of methyldopa)
3) Levothyroxine ↓ (decreased efficacy of levothyroxine)
4) Penicillamine ↓ (chelates with iron)
5) Fluoroquinolones ↓ (forms ferric ion– quinolone complex)
6) Tetracycline and doxycycline ↓ (when administered within 2
hours of iron salt)
7) Mycophenolate ↓ (decreases absorption)

29. Causes of treatment failure for IDA
1) Poor patient adherence
2) Inability to absorb iron
3) Incorrect diagnosis
4) Continued bleeding

30. PARENTERAL IRON THERAPY
 Parenteral therapy is taken when:
1) Evidence of iron malabsorption
2) Intolerance to orally administered iron
3) Long term non adherence
4) Patients who cannot take oral iron therapy
5) Patients with significant blood loss who refuse iron therapy.
PREPARATIONS
1) Iron Dextran; 50mg iron/ml
2) Sodium ferric gluconate; 2.5mg iron/5ml
3) Iron sucrose; 20mg iron/ml

32. TRANSFUSIONS
Transfusion of allogenic blood is indicated in acute situations
of blood loss when hemodynamic support is needed.
Blood transfusion in chronic anemia can elevate Hb
concentration
An exception to this treatment option is patients who have
developed low Hct values over extended time periods. These
patients often demonstrate cardiac compromise after
transfusion despite Hct levels is in the 20% range. These
patients should receive iron therapy, followed by transfusion
only if necessary.

33. PATIENT CARE
Take iron products with or after meals – reduces the incidence
of nausea.
Patient should be told that their faeces may be of come dark
colored.
Discuss about the length of treatment and adherence to the
therapy.

34. Megaloblastic Anemia
Macrocytic anemia is divided into two types:
1. Megaloblastic anemia
2. Non megaloblastic anemia
The two major causes are:
1. Folate deficiency
2. Vitamin B12 deficiency
Pernicious anemia is a specific disease caused by malabsoption of
Vit. B12.
Important to distinguish B12 from folate deficiency.

35. Stages of B12 deficiency
Stage B12conc. Mean corpuscular Hb Signs &
vol. Symptoms
Normal Normal Normal Normal None
-ve bal. ” ” ” ”
Depletion of
Stores Slight ↓ ” ” Possible
B12 def. Moderate ↓ ↑ ” ”
Erythropoiesis
B12 def.
Anemia Severe ↓ ↑ ↓ Probable

36. Etiology of Vitamin B12 Deficiency
The three major causes are:
1. Inadequate intake
2. Malabsorption syndrome
3. Inadequate utilization
Deficiency occurs from inadequate intake or malabsorption.
The only dietary source of Vit. B12 (cyanocobalamin) is from
food of animal origin. It is present in meat, fish, eggs, cheese
and milk. Daily requirements are between 0.5-1.0 μg.
Malabsorption occurs if the distil ileum is removed during
stagnant loop syndrome, tropical sprue and fish tapeworm
infestation.
Drugs also cause malabsorption.

37. Pathophysiology of Vitamin B12
Vitamin B12 works closely with folate in the synthesis of
building blocks for DNA and RNA.
 It is a water soluble vitamin obtained exogenously by
ingestion of meat, fish, poultry, diary products and fortified
cereals.

38. Most circulating
cobalamin complex
Free cobalaminFree cobalamin
Binding complexBinding complex
Cobalamin – R- Protein
complex
Cobalamin – R- Protein
complex
Release of cobalaminRelease of cobalamin
StomachStomach
Dietary cobalaminDietary cobalamin
Complex secreated
into circulation
Mucosal cell receptors
(cubilin) in distal ileum
Cobalamin -Intrinsic factor
complex
Cobalamin -Intrinsic factor
complex
Pepsin and HCL
R- Protein
Cobalamin -R- Protein complex
from Bile
Degradation by pancreatic
enzymes
Intrinsic factor

39.  Gastrectomy – Vit. B12 deficiency
 Vit. B12 deficiency Deposition of
methyltetrahydrofolate prevent DNA synthesis
 Defect in methylation reaction, needed for myelin
formation leads to neuropathy.
 Alternate mechanism involves diffusion.

40. Investigation
Vit. B12
MMA, Hcy conc. and renal function
Schilling test and hematology
Clinical manifestations
• Macrocytosis
• Anisocytosis(cells of unequal size)
• Poikilocytosis(misshapen red cells)
• Thrombocytopenia
• Enlarged Spleen (spleenomegaly), Slight fever
• Mild jaundice and progressive neuropathy

41. Symptoms
Apathy
Weakness
Fatigue
Palpitation
Breathlessness
Sore tongue
Glossitis
Burning of mouth
Nausea
Heart burn

42. Treatment
Goals
1. Reversal of hematologic manifestations
2. Replacement of body stores
3. Prevention or resolution of neurologic manifestations
Dietary intake
Oral administration of Vit.B12 (1-10µg/day cyanacobalamin)
Parenteral administration (100-1000ug deep sc)
Intranasal administration(400µg 3 times a week)

43. Adverse effect
1. Hyperuricemia and hypokalemia
2. Rebound thrombocytosis precipitate thrombotic events
3. Fluid retention in pateints with compromised CV status
4. Rare case of anaphylaxis with parenteral administration

44. FOLIC ACID Deficiency
Most common Vitamin deficiency
Critical in early pregnancy
The four major causes are:
1. Inadequate intake of folic acid
2. Decreased absorption
3. Hyper utilization
4. Inadequate utilization
5. Drugs (Azathioprine, methotrexate, phenytoin etc…)
Etiology of Folic acid Deficiency

45. Pathophysiology
GI cells and RBCGI cells and RBC
Methyltetrahydrofolate
monoglutamate
Methyltetrahydrofolate
monoglutamate
FolateFolate
MonoglutamateMonoglutamate
PolyglutamatePolyglutamate
Dietary FolateDietary Folate
Dihydrofolate
Enzymes in the gut
Absorption
Methylation/ Reduction
Specific carrier
Methyl
FolateFolate
Polyglutamate
DHF Reductase

46. Polyglutamate prevents folate leaking out of cell
Folate – coenzyme for DNA and RNA synthesis
Defective DNA synthesis affect GI cells and RBC – sore
tongue and anemia
Daily requirement- 50-100µg
In pregnancy additional 400µg/day recommended
Average amount of stores- 5-10mg

47. Clinical manifestation
1. Megaloblastosis
2. Glossitis
3. Diarrhea
4. Weight loss
5. Fatigue
6. Pallor
7. palpitation
8. Chronic folate deficiency predisposes patients to thrombosis,
depression and neoplasia

48. Investigation
1. Serum/erythrocyte Folate level
2. Increased plasma Hcy conc., RFT
3. Peripheral blood- large oval red cells
4. Anisocytosis and poikilocytosis
5. Hypersegmented neutrophils, thrombocytopenia

49.  Therapy consist of :
1. Administration of exogenous folic acid
2. Replace body stores
3. Resolve signs and symptoms
 Dietary intake
 Oral preparations (1mg daily)
 Parenteral administration(5mg/ml im/iv/sc)
Treatment

50. Hemolytic Anemia
Hemolytic anemia decreases the life span of erythrocytes
If the rate of destruction of the erythrocytes exceeds the
rate of production, then anemia results
Wide range of hemolytic anemia with both genetic and
acquired disorders

51. Classification of Hemolytic Anemia
1. Abnormalities of red blood cell interior
a.) Enzyme deficts
b.) Hemoglobinopathies
2. RBC membrane abnormilities
a.) Heridity spherocytosis
b.) Paroxyysmal nocturnal hemoglobinuria
c.) Spur cell anemia
3. Extrensic factors
a.) Splenomegaly
b.) Antibody immune hemolysis
c.) Microanglopathic hemolysis
d.) Infections, toxins etc.
Intra-
corpuscular
Extra-
corpuscular
Hereditary
Acquired

52. Etiology
1. Sickle cell anemia:
 It is due to abnormal hemoglobin called hemoglobin S (HbS),
normal hemoglobin is usually HbA
 α chains are normal and β chains are abnormal. HbS has
valine substituted for glutamic acid as the 6th
amino acid in the
β polypeptide compared with HbA
 The molecules of HbS polymerize into long chain and
precipitate inside the cells because of this RBC’s attain sickle
shape and become more fragile leading to hemolysis
 Hemolysed sickle cell aggregate and block the blood vessels
leading to infarction.

53. 2. Thalassaemias
It is also known as Cooley’s anemia or Mediterranean anemia
(more common in Thailand and Mediterranean countries)
Due to inherited abnormalities of hemoglobin
It is of two types
1. α Thalassaemias
2. β Thalassaemias (more common)
Defective synthesis of globin genes
Production of α and β chains become imbalanced
Precipitation of polypeptide Precipitation of polypeptide
chain in the immature RBC chain in the mature RBC
Disturbance in the process Hemolysis

54. α Thelassaemia (fetal life) β Thelassaemia
α chains are less, absent or β chains are less, absent or
abnormal with excess of abnormal with excess of
γ chains. α chains.
Defective Erythropoiesis and Hemolysis
G6PD deficiency:
G6PD is an erythrocyte enzyme that is indirectly involved in the
production of reduced Glutathione.
Glutathione is produced in response to and protects the red cells
from oxidizing reagents.

55. Pathophysiology
Normal 120 days life span of RBC (comes from its inherent
flexibilityin passing through the microvasculature and spleen
without disruption of cell membrane or sesquestration and
phagocytosis by reticuloendothelial cells)
Hemolysis RBC lifespan less than 120 days due to
1. Membrane defects
2. Alteration in hemoglobin solubility or stability
3. Changes in intracellular metabolic process
These changes can be intrinsic or extrinsic in origion
Intracorpuscular changes Extracorpuscular changes are
are genetically determined cause of hemolytic anemia

56. Hereditary spherocytosis: RBC’s lose their flexible biconcave
characteristics and become tight spheres destroyed by
reticuloendothilial cells, causing pigment bile stones, mild
jaundice and splenomegaly.
Sickle cell and Thelassaemia: Alteration in hemoglobin solubility
and stability cell deformation hemolysis
Some red cells in patients with sickle cell disease contain fetal
hemoglobin (HbF). These cells do not sickle.
G6PD Deficiency
G6PD deficiency i.e. decrease in G6PD
Decrease production of NADPH in erythrocytes
NADPH is needed to keep glutathione in reduced form
Hemoglobin in reduced from and helps erythrocytes deal with
oxidative stress

57. Clinical Manifestation
Acute haemolytic anemia:
1. Malaise
2. Fever
3. Abdominal pain
4. Dark urine and jaundice
5. Haemoglobulinaemia
6. Hyperbilinaemia
7. Reticulocytosis
8. Increased urobilinogen levels in urine
Chronic haemolytic anemia:
1. Splenomegaly
2. Normochromic and normocytic anemia

58. Investigation
1. Sickle cell disease: abnormal hemoglobin electrophoresis
The proportion of hemoglobins is a useful monitoring
parameter.
2. Thalassaemia: Hemoglobin electrophoresis
3. G6PD deficiency:
Treatment
1. Sickle cell anemia:
 Patients with sickle cell disease have a high evidence of
Pneumococcal infections
 Penicillin V (Phenoxymethyl penicillin): 250mg twice a day
usually for adults
 Erythromycin being used for patients allergic to penicillin.

59. Administration of pneumococcal vaccine and haemophilus
influenza vaccine is now common
Increased proportion of HbF and decreased proportion of HbS on
the circulation
Drugs that may increase fetal Hb production
1. 5- Azacytidine
2. Cytarabine
3. Vinblastin
4. Hydroxycarbamide (Hydroxyurea) Cytotoxicity
5. Eruthropoietin
6. Short chain fatty acids (Valproate etc.)
Transfusions and exchange transfusions have also used to decrease
the proportion of Hbs. This is limited by the usual complications of
chronic infusions.

60. Iron overload the risk of blood borne virus transmission and
sensitization.
Strong opioids are required for pain relief. Morphine is a more
logical choice of opioids.
2. Thalassaemia:
No effective treatment for thalassemia
Desferrioxamine and Deferiprone are routinely needed.
Binds with free iron and Oral, but it is reported to cause
Iron bound to ferritin(serum reversible neutropenia so given
Ferritin reaches 1000ug/l) to pateints who are intolerant to
Desferrioxamine

61. Splenectomy
Drugs increases HbF: combination of drugs
Hydroxycarbamide (hydroxyurea) and erythropoietin
3. G6PD deficiency:
No specific treatment
During acute episodes the patient should be kept well hydrated
to ensure good urine output thus preventing Hb damaging the
kidney
Blood transfusion

62. Patient care
1. Sickle Cell
 Encourage to take their prophylactic penicillin and folic acid
therapy regularly
 Opioid addiction are prevented by giving analgesic
treatments recognize that the crises are extremely painful and
patient requires effective analgesia
2. Thalassaemia
 Need to educate the patient regarding the cytotoxic nature of
hydroxycarbamide (hydroxyurea)
3. G6PD deficiency
 Patients can be given a list of drugs to avoid
 Drug therapy does not play a large part in the management.

63. Anemia of CHRONIC DISEASE
It is an hypoproliferative anemia that has traditionally been
associated with infections, inflammatory, hepatic disease or
neoplastic disease lasting for more than 1 to 2 months.
ACD is a response to stimulation of the cellular immune
system by various underlying disease processes. ACD
commonly develops in AIDS patients, especially those with
opportunistic infections or malnutrition, HIV infects
hematopoietic cells, which can lead to abnormal hematopoiesis
and bone marrow suppression. In addition, the drugs used to
treat AIDS and associated illness can cause bone marrow
suppression.
Etiology

65. Pathophysiology
In this anemia RBC’s have shortened life span
Bone marrows capacity to respond to EPO is inadequate to
maintain normal Hb concentration
This anemia may be due to a block in release of iron from the
endothilial cells of the marrow
Cytokinins such as IL1, γ interferron and tumor necrosis factor
released during these illness may inhibit the production or
action of EPO or the production of RBCs

66. Signs and Symptoms
1. Fatigue
2. Breathlessness
3. Swollen feet
4. Chest pain
5. Decreased mental activity
Laboratory findings
1. Serum iron level
2. Bone marrow examination

67. Treatment
Recovery from the anemia usually occurs with resolution of
the underlying process. During inflammation Iron(Fe) therapy
is ineffective by either oral or parenteral route.
Exogenous EPO (recombinant human EPO or epoetin alpha)
has been used to stimulate erythropoiesis in patients with
chronic disease.
The epoetin alpha 150 units/kg given subcutaneously three
times weekly is effective.
Most patients tolerate epoetin alpha therapy well.
Iron deficiency can occur in patients treated with epoetin alpha

68. However close monitoring of iron level is necessary during
epoetin alpha therapy
Oral iron supplementation should be given if transferrin
saturation drops to 20% or the serum ferritin level drops below
100u/L
More common toxicities of epoetin alpha are fever, bone pain
and fatigue.

69. Aplastic Anemia
It is group of disorders characterized by pancytopenia in
peripheral blood, vairiable hypocellularity in bone marrow,
absence of underlying malignent or myeloproliferative disease.
ETIOLOGY
1. Congenital – rare
2. Acquired- virus or chemical
Other etiologies
Hepatitis, infectious mononucleosis, dengue and influenza
Regular exposure to irradiation
Major component of inherited conditions

70. Causes
Damage to the bone marrow's stem cells causes
aplastic anemia. When stem cells are damaged, they
don't grow into healthy blood cells.
The cause of the damage can be acquired or
inherited. Acquired aplastic anemia is more
common, and sometimes it's only temporary.
Aplastic anemia that's inherited is rare.
In more than half of the people who have aplastic
anemia, the cause of the disorder is unknown. Some
research suggests that stem cell damage may occur
because the body's immune system attacks its own
cells by mistake.

71. Acquired Causes
A number of diseases, conditions, and factors
can cause aplastic anemia, including:
Toxins, such as pesticides, arsenic, and benzene
Radiation and chemotherapy (treatments for
cancer)
Medicines, such as chloramphenicol (an
antibiotic rarely used in the United States)
Infectious diseases, such as hepatitis, Epstein-
Barr virus, cytomegalovirus (si-to-MEG-a-lo-VI-
rus), parvovirus B19, and HIV

72. Autoimmune disorders, such as lupus and
rheumatoid arthritis
In some cases, cancer from another part of the
body can spread to the bone and cause aplastic
anemia.

73. Inherited Causes
Certain inherited conditions can damage the
stem cells and lead to aplastic anemia. Examples
include Fanconi anemia, Shwachman-Diamond
syndrome, dyskeratosis congenita, and
Diamond-Blackfan anemia

74. RISK FACTORS OF APLASTIC
ANEMIA
Aplastic anemia is a rare, but serious blood
disorder. In the United States, about 500–1,000
people develop this type of anemia each year.
The disorder is two to three times more common
in Asian countries.
People of all ages can get aplastic anemia.
However, it's most common in adolescents,
young adults, and the elderly. Men and women
are equally likely to have it.
 risk for aplastic anemia is higher if :

75. Taken certain medicines or had radiation or
chemotherapy treatment (treatments for cancer)
Been exposed to toxins
Certain infectious diseases, autoimmune
disorders, or inherited conditions

76. SIGN AND SYMPTOMS
Low numbers of red blood cells, white blood
cells, and platelets cause most of the signs and
symptoms of aplastic anemia.
Signs and Symptoms of Low Blood Cell Counts
The most common symptom of a low red blood
cell count is fatigue (feeling tired or weak). Not
having enough hemoglobin in the blood causes
fatigue. Hemoglobin is an iron-rich protein in
red blood cells that carries oxygen to the body.

77. A low red blood cell count also can cause
shortness of breath; dizziness, especially when
standing up; headache; coldness in your hands or
feet; pale skin, gums, and nail beds; and chest
pain.
If you don't have enough hemoglobin-carrying
red blood cells, your heart has to work harder to
circulate the reduced amount of oxygen in your
blood. This can lead to arrhythmias, heart
murmur, an enlarged heart, or even heart failure.

78. White blood cells help fight infections. Signs and
symptoms of a low white blood cell count include
fevers, frequent infections that can be severe,
and flu-like illnesses that linger.
Platelets stick together to seal small cuts on
blood vessel walls and stop bleeding. People who
have low platelet counts tend to bruise and bleed
easily, and the bleeding may be hard to stop.

79. Types Common of bleeding linked to a low
platelet count include nosebleeds, bleeding
gums, pinpoint red bleeding spots on the skin,
and blood in the stool. Women also may have
heavy menstrual bleeding.
Paroxysmal Nocturnal Hemoglobinuria
About one-third of people who have aplastic
anemia have a condition called paroxysmal
nocturnal hemoglobinuria (PNH). This is a red
blood cell disorder. Most people who have PNH
don't have any signs or symptoms.

80. OTHER SIGN SYMPTOMS
Aplastic anemia can cause signs and symptoms
that aren't directly related to low blood cell
counts. Examples include nausea (feeling sick to
your stomach) and skin rashes.
Shortness of breath
Swelling or pain in the abdomen or swelling in
the legs caused by blood clots
Blood in the urine
Headache
Jaundice

81. Pathogenesis
It involves destruction inhibition or impairment of
stem cells, development of abnormal micro cells or
lack f hemopoietic co factores.
Exogenous agents(virus,drug,metabolites)
inter the body
attaches to hemopoietic stem cells
agent-stem cell combination stimultus auto immune
procesm cells
distroy stem

82. Recovery may occurs with termination of immune
process and regeneration of patient stem cells .
If auto immune process continues
immunosuppressive therapy alone may be effective
or followed by marrow transplantation .
Drug included marrow aplasia –dose related or
idiosyncratic.
Chloramphenicol best drug given by oral, I.M,I.V and
topical administration.

83. Treatment
Treatments for aplastic anemia include blood transfusions,
blood and marrow stem cell transplants, and medicines.
These treatments can prevent or limit complications,
relieve symptoms, and improve quality of life.
In some cases, a cure may be possible. Blood and marrow
stem cell transplants may cure the disorder in people who are
eligible for a transplant. Removing a known cause of aplastic
anemia, such as exposure to a toxin, also may cure the
condition.
Needs of Treatment
People who have mild or moderate aplastic anemia may not
need treatment as long as the condition doesn’t get worse.
People who have severe aplastic anemia need medical
treatment right away to prevent complications.
People who have very severe aplastic anemia need emergency
medical care in a hospital. Very severe aplastic anemia can
be fatal if it's not treated right away.

84. Blood Transfusions
People who have aplastic anemia may need blood
transfusions to keep their blood cell counts at acceptable
levels.
A blood transfusion is a common procedure in which blood is
given to you through an intravenous (IV) line in one of your
blood vessels. Transfusions require careful matching of
donated blood with the recipient’s blood.
Blood transfusions help relieve the symptoms of aplastic
anemia, but they’re not a permanent treatment.
Blood and Marrow Stem Cell Transplants
A blood and marrow stem cell transplant replaces damaged
stem cells with healthy ones from another person (a donor).
During the transplant, which is like a blood transfusion, you
get donated stem cells through a tube placed in a vein in your
chest. Once the stem cells are in your body, they travel to
your bone marrow and begin making new blood cells.
Blood and marrow stem cell transplants often cure aplastic

85. Medicines
If you have aplastic anemia, your doctor may prescribe
medicines to:
•Stimulate your bone marrow
•Suppress your immune system
•Prevent and treat infections
Medicines To Stimulate Bone Marrow
Man-made versions of substances that occur naturally in the
body can stimulate the bone marrow to make more blood cells.
Examples of these types of medicines include erythropoietin
(e-RITH-ro-PO-e-tin) and colony-stimulating factors.
These medicines have some risks. You and your doctor will
work together to decide whether the benefits of these
medicines outweigh the risks. If this treatment works well, it
can help you avoid the need for blood transfusions.

86. Medicines To Suppress the
Immune System
Three medicines—often given together—can
suppress the body’s immune system. They are
antithymocyte globulin (ATG), cyclosporine, and
methylprednisolone.
People who have aplastic anemia may need long-
term treatment with these medicines.
Medicines that suppress the immune system can
have side effects. They also may increase the risk
of developing leukemia (lu-KE-me-ah) or
myelodysplasia (MI-e-lo-dis-PLA-ze-a; MDS).
Leukemia is a cancer of the blood cells. MDS is a
condition in which the bone marrow makes too

87. Ongoing Care
Treatment for aplastic anemia may cause side
effects or complications.
People who have aplastic anemia may be at
higher risk for infection due to low white blood
cell counts. For example, you may want to:
Stay away from people who are sick and avoid
large crowds of people.
Avoid certain kinds of foods that can expose you
to bacteria, such as uncooked foods.
Wash your hands often.
Brush and floss your teeth and get regular dental
care to reduce the risk of infection in your mouth
and throat.
Get a yearly flu shot and pneumonia vaccine.

88. dose regimen
I.V ALG (10 mg/kg) for five alternate days.
I.V methyl prednisolone (8mg /kg/day) or
2mg/kg/day over 9 days.
Oral prednisolone (1.25mg/kg/day) from day 10 -15
declining to 0.1mg /kg /day from days 3-4.

89. Acetaolamide dapsone quinidine
 aspirin diclofenac sulfonamide
Captopril indometacin
Carbamazpine phenytoin chloramphenicol
oxyphenbutazone