By: Dinsy Paul Juliet James Priya K Sravan Kumar. Potturi Govinda Ajmera
By: Dinsy Paul Juliet James Priya K Sravan Kumar. Potturi Govinda Ajmera
By: Dinsy Paul Juliet James Priya K Sravan Kumar. Potturi Govinda Ajmera
Dinsy Paul
Juliet James
Priya K
Sravan Kumar. Potturi
Govinda Ajmera
DEFINITION
Anemias 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 to the
levels that are required for adequate tissue
oxygenation or which results in decreased oxygen-
carrying capacity of the blood.
Anemias are often a sign of underlying pathology.
Therefore a rapid diagnosis of the cause of the anemia
is essential.
Anemias can result from :
1) Faintness
2) Fatigue
3) Dizziness
4) Irritability
5) Malaise
6) Palpitation
7) Headache
8) Shortness of breath
9) Angina
10) Ankle edema
Treatment of IDA
Aim of treatment is to correct the anemia and replenish iron
stores.
Treatment of IDA consist of 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.
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.
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
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)
Causes of treatment failure for IDA
1) Poor patient adherence
2) Inability to absorb iron
3) Incorrect diagnosis
4) Continued bleeding
PARENTERAL IRON THERAPY
PREPARATIONS
1) Iron Dextran; 50mg iron/ml
2) Sodium ferric gluconate; 2.5mg iron/5ml
3) Iron sucrose; 20mg iron/ml
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.
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.
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.
Stages of B deficiency
12
-ve bal. ” ” ” ”
Depletion of
Stores Slight ↓ ” ” Possible
B12 def.
Anemia Severe ↓ ↑ ↓ Probable
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.
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.
Dietary cobalamin
Stomach
Pepsin and HCL
Release of cobalamin
R- Protein
Cobalamin – R- Protein
complex
Cobalamin -R- Protein complex
from Bile
Binding complex
Degradation by pancreatic
enzymes
Free cobalamin
Intrinsic factor
Cobalamin -Intrinsic factor
complex Most circulating
cobalamin complex
Clinical manifestations
• Macrocytosis
• Anisocytosis(cells of unequal size)
• Poikilocytosis(misshapen red cells)
• Thrombocytopenia
• Enlarged Spleen (spleenomegaly), Slight fever
• Mild jaundice and progressive neuropathy
Symptoms
Apathy
Weakness
Fatigue
Palpitation
Breathlessness
Sore tongue
Glossitis
Burning of mouth
Nausea
Heart burn
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)
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
FOLIC ACID Deficiency
Most common Vitamin deficiency
Critical in early pregnancy
Dihydrofolate Polyglutamate
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
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
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
Treatment
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)
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
Classification of Hemolytic Anemia
1. Abnormalities of red blood cell interior
a.) Enzyme deficts
b.) Hemoglobinopathies
Intra-
corpuscular 2. RBC membrane abnormilities Hereditary
a.) Heridity spherocytosis
b.) Paroxyysmal nocturnal hemoglobinuria
c.) Spur cell anemia
3. Extrensic factors
a.) Splenomegaly
Extra- b.) Antibody immune hemolysis Acquired
corpuscular
c.) Microanglopathic hemolysis
d.) Infections, toxins etc.
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.
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
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.
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
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.
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.)
2. Thalassaemia:
No effective treatment for thalassemia
Desferrioxamine and Deferiprone are routinely needed.
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
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.
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.
Etiology
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.
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
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
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
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.
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
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.
Acquired Causes