2. INTRODUCTION: ANAEMIA
• Anemias are a group of diseases characterized by a decrease in
hemoglobin (Hb) or red blood cells (RBCs), resulting in decreased
oxygen-carrying capacity of blood.
• The World Health Organization defines anemia as Hb less than 13 g/dL
(<130 g/L; <8.07 mmol/L) in men or less than 12 g/dL (<120 g/L; <7.45
mmol/L) in women.
• The oxygen carrying capacity of the blood is therefore decreased.
• Red blood cells carry hemoglobin, an iron-rich protein that attaches to
oxygen in the lungs and carries it to tissues throughout the body.
3. CONT…
• Anemia is sign not diagnosis.
• There are many kind of anemia, each with its own cause. It is
characterized by insufficient erythrocytes or hemoglobin.
• Loss of blood is the most common cause of anemia.
• Anemia can be temporary or long term, and it can range from mild to
severe.
• These condition leads to fatigue and intolerance to cold, which related to
lack of oxygen needed for energy and heat production, and paleness
which is due to low hemoglobin content.
4. AETIOLOGY OF ANAEMIA
Two different mechanisms work:
• Increased haemoglobin loss due to either:
– hemorrhage (red cell loss) or
– haemolysis (red cell destruction).
• Reduced haemoglobin synthesis due to either:
– lack of nutrient
– bone marrow failure.
5. Classification of Anaemias
• Two of the widely accepted classifications are based on the pathophysiology
and morphology
PATHOPHYSIOLOGIC CLASSIFICATION
Anaemia due to blood loss.
a) Acute post haemorrhagic anaemia
b) Chronic blod loss.
Anaemia due to impaired red cell formation
MORPHOLOGIC CLASSIFICATION
• Microcytic, hypochromic
• Normocytic, normochromic
• Macrocytic, normochromic
8. IRON DEFICIENCY ANAEMIA
• Iron deficiency anaemia is a common type of anaemia a condition in
which blood lacks adequate healthy red blood cells due to iron
deficiency.
• Red blood cells supply oxygen to the whole body. Without enough
amount of iron body can’t produce enough of haemoglobin.
• As a result, iron deficiency anaemia produces tiredness and shortness
of breath.
• Iron is distributed in active metabolic and storage pools. Total body
iron is about 3.5 g in healthy men and 2.5 g in women.
9. CONT…
The distribution of body iron is:
• Hb: 2 g (men), 1.5 g (women)
• Ferritin: 1 g (men), 0.6 g (women)
• Haemosiderin: 300 mg.
• Myoglobin: 200 mg.
• Tissue enzymes (haeme and non-haeme): 150 mg
• Transport-iron compartment: 3 mg.
10. CONT…
• Iron is absorbed in the duodenum and upper jejunum. Dietary iron is
usually in the ferric state which needs its conversion to ferrous state
for absorption.
• Iron from intestinal mucosal cells is transferred to transferrin, an iron
transport protein synthesized in the liver; transferrin can transport iron
from cells (intestinal, macrophages) to specific receptors on
erythroblasts, placental cells, and liver cells.
• For haeme synthesis, transferrin transports iron to the erythroblast
mitochondria, which insert the iron into protoporphyrin for it to
become haeme.
11. CONT…
• Iron is stored in 2 forms, ferritin and haemosiderin.
• The most important is ferritin, which is a soluble and active storage
fraction located in the liver cells, bone marrow, spleen, in RBCs and
in serum.
• The second storage pool of iron is in haemosiderin, which is relatively
insoluble and is stored primarily in the liver (in Kupffer cells) in bone
marrow (in macrophages).
12.
13. Transport, utilization, storage and excretion
↓
Iron on entering plasma is immediately converted to the ferric form and
complexed with a glycoprotein transferrin (Tf).
↓
Iron is transported into erythropoietic and other cells through attachment of
transferrin to specific membrane bound transferrin receptors(TfRs).
↓
The complex is engulfed by receptor mediated endocytosis. Iron dissociates
from the complex at the acidic pH of the intracellular vesicles.
↓
The released iron is utilized for hemoglobin synthesis or other purposes.
Tf and TfRs are returned to the cell surface to carry fresh loads.
14. Dietary sources
• Rich : Liver, egg yolk, oyster, dry beans, dry fruits, wheat germ, yeast.
• Medium : Meat, chicken, fish, spinach, banana, apple.
• Poor : Milk and its products, root vegetables
Epidemiology
• Iron deficiency anaemia is the commonest form of anaemia worldwide and
may be present in up to 20% of the world's population.
• A diet deficient in iron, parasitic infestations, for example, hookworm
(causing blood loss), and multiple pregnancies contribute to its high
prevalence in underdeveloped countries.
• Even in Western societies, it has been reported that as many as 20% of
menstruating females show a rise in Haemoglobin levels on iron therapy.
15. Aetiology
• The commonest cause of iron deficiency is due to blood loss.
• In women of childbearing age, this is most commonly due to menstrual loss.
• Amongst adult males, the most likely cause is gastro-intestinal bleeding.
• Other causes of blood loss associated with iron deficiency anaemia include
haemorrhoids, nose bleeds or postpartum haemorrhage.
Major Causes of Iron Deficiency Anaemia
• Inadequate iron absorption
Dietary deficiency
Malabsorption
• Increased physiological demand
• Loss through bleeding
16. Pathophysiology
• IDA is a hypochromic-microcytic anemia – red blood cells (RBCs) are
abnormally small with low levels of hemoglobin (hb)
• Despite the cause, IDA occurs when the body’s iron demand exceeds
that of it’s supply.
• Two types: iron store depletion vs. metabolic/functional
• Inflammatory response of body in response to infection may also
contribute to an acute form of IDA
17. • How quickly IDA develops depends on cause, but develops in three
stages
• Without enough iron, the body uses up all the iron it has stored in the
liver, bone marrow and other organs.
• Once the stored iron is depleted, the body is able to make very few
RBCs. If erythropoietin is present without sufficient iron, there is
insufficient fuel for RBC production.
• The red blood cells that the body is able to make are abnormal and do
not have a normal hemoglobin carrying capacity, as do normal red
blood cells.
18. Iron Store Depletion
Inadequate dietary intake
• Diets low in meat, fish, beans, or iron-fortified foods – commonly
seen with vegetarians or individuals living in poverty
• Mechanism – low iron stores leads to demand > supply
Excessive blood loss
• Hemorrhage, menorrhagia (heavy menstrual bleeding)
• Mechanism – depleting iron stores faster than replacing combined
while increasing body’s demand for iron
19. Metabolic/Functional
Insufficient iron delivery to bone marrow
• Iron stores adequate to meet body’s need
• Mechanism – delivery to bone marrow to be utilized in the production
of RBCs is impaired
Impaired use of iron within bone marrow
• Iron stores adequate to meet body’s need
• Mechanism – even when delivered, there is impaired use of iron in the
bone marrow to produce RBCs
20.
21. Pathophysiology:
Stages of Development
Stage 1
• It is characterized by decreased bone marrow iron stores.
• Level of iron in Hb and serums remain normal, but the serum ferritin level
falls
Stage 2
• Erythropoiesis is impaired, when serum iron falls to below 50 μg/dL.
• Reduction in iron transport to bone marrow, causing iron deficient RBC
production (hemoglobin content of RBC is reduced)
Stage 3
• Small, hemoglobin-deficient cells enter circulation, replacing normal RBC.
• Development of microcytosis (small sized RBCs) and hypochromia (faint
coloured RBCs)
22. Clinical manifestations
• The color of the skin is unreliable.
• Patients at risk of heart failure may present with breathlessness when
anaemic.
• Koilonychia, dysphagia and pica are found only after chronic iron
deficiency and are relatively rare.
• The usual symptoms are weakness, fatigue, dyspnoea on exertion,
palpitations and pallor of the skin, mucous membranes and sclerae.
• Older patients may develop angina and congestive cardiac failure.
• Menorrhagia is a common symptom in iron deficient women.
23. RISK FACTORS
These groups of people may have an increased risk of iron deficiency
anaemia:
Women: Because women lose blood during menstruation, women in
general are at greater risk of iron deficiency anaemia.
Infants and children: Infants, who were low birth weight or born
prematurely, who don’t get enough iron from breast milk or formula
may be at risk of iron deficiency.
Vegetarians: People who don’t eat meat may have a greater risk of
iron deficiency anaemia if they don’t eat other iron-rich foods.
Frequent blood donors: People who routinely donate blood may have
an increased risk of iron deficiency anaemia since blood donation can
deplete iron stores.
24. DIAGNOSIS
• Examination of the upper and lower tract is an important investigation. This
may include upper gastro- intestinal tract endoscopy, colonoscopy, barium
enema (X-ray of the colon and rectum) and small bowel biopsy.
• Complete blood count (CBC)
• A test to determine the size and shape of red blood cells
• Additional tests
26. Treatment
• Prophylaxis of iron deficiency anaemia
• Iron supplementation to correct anaemia and replenish stores.
• Oral iron in the ferrous form is cheap, safe and effective in most patients.
Depending on the state of the body's iron stores, it may be necessary to
continue treatment for up to 6 months to both correct the anaemia and
replenish body stores.
• The standard treatment is ferrous sulphate 200 mg two to three times a day.
• It typically takes between 1 and 2 weeks for the haemoglobin level to rise 1
g/dL.
• Parenteral iron therapy in iron deficiency anaemia should be reserved for
patients who fail on oral therapy, usually because of poor adherence or
intolerable gastro intestinal side effects.
• Patients who have lost blood acutely may require blood transfusions
27. CONT…
• Iron dextran may also be
given by deep intramuscular
injection.
Intravenous iron should not be
given during acute bacterial
infections, since it may stimulate
bacterial growth.
• As intravenous iron significantly
reduces the oral absorption of
iron, there is no rationale for
giving oral iron for several days
after administering intravenous
iron.
29. MEGALOBLASTIC ANAEMIA
• The megaloblastic anaemias are disorders caused by impaired DNA
synthesis and are characterised by a distinctive abnormality in
the hematopoietic precursors in the bone marrow in which the
maturation of the nucleus is delayed relative to that of the
cytoplasm.
• Megaloblasts are both morphologically and functionally abnormal
with the result that the mature red cells formed from them and
released into the blood are also abnormal in shape and size, the
most prominent abnormality being macrocytosis.
30. • The underlying defect for the asynchronous maturation of the
nucleus is defective DNA synthesis due to deficiency of vitamin
B12 (cobalamin) and/or folic acid (folate).
• Less common causes are interference with DNA synthesis by
congenital or acquired abnormalities of vitamin B12 or folic
acid metabolism.
• In addition to abnormal red cells, the white cells and platelets
may be affected.
31. WHAT IS MEGALOBLASTIC ANAEMIA
• Megaloblastic anaemia is a type of anaemia characterized by the
formation of unusually large, abnormal and immature red blood cells
called as megaloblasts by the bone marrow, which are released into the
blood.
• Anemia is based on ineffective erythropoiesis.
• These red cells are large in shape
The two major causes are folate deficiency and vitamin B12 deficiency.
• Pernicious anaemia is a specific autoimmune disease that causes
malabsorption of vitamin B12 due to a lack of intrinsic factor.
32. EPIDEMIOLOGY
Folate deficiency anaemia
• Much of the world's population has a marginal dietary intake of
folate. Body stores are low, and as soon as there is a decrease in
dietary intake or there is increased folate demand, deficiency readily
occurs.
Vitamin B12 deficiency anaemia
• Strict vegans (e.g. Hindus) commonly have low vitamin B12 levels due
to their dietary deficiency.
33. AETIOLOGY
Folate deficiency anaemia
• Folate is readily available in a normal diet. Fruit, green vegetables and yeast all
contain relatively large amounts of folate.
• Alcoholism
• Malabsorption
• Deficiency of thiamine and factors (e.g. enzymes) responsible for folate metabolism
• Increased needs in Pregnancy, infant, rapid cellular proliferation and cirrhosis.
Vitamin B12 deficiency anaemia
• Deficiency occurs from inadequate intake or malabsorption.
• The only dietary source of vitamin B12 (cyanocobalamin) is from food of animal
origin. It is present in meat, fish, eggs, cheese and milk.
• Deficient intrinsic factor
• Coeliac disease
• Chronic pancreatitis
34. FOLATE DEFICIENCY ANAEMIA:
PATHOPHYSIOLOGY
Dietary folate conjugated to polyglutamic acid.
↓
Polyglutamate form converted to monoglutamate form by the enzymes present in the gut.
↓
Further converted to tetrahydrofolate form.
↓
The folate eventually acts as a coenzyme involved in a number of reactions including DNA and
RNA synthesis.
↓
During DNA synthesis, the folate coenzyme is oxidized to the dihydrofolate form, which is
inactive and has to be reactivated by the enzyme dihydrofolate reductase.
↓
The enzyme inhibited by methotrexate and to a lesser extent by trimethoprim and pyrimethamine.
35.
36. VIT. B12 DEFICIENCY ANAEMIA:
PATHOPHYSIOLOGY
Enzymes in the stomach release vitamin B12 from protein complexes
↓
One molecule of vitamin B12 then combines with one molecule of a glycoprotein called
intrinsic factor.
↓
The vitamin B12 enters the ileal cell and is then transported through the blood attached to
transport proteins.
↓
Vitamin B12 is a coenzyme for the removal of a methyl group from
methyltetrahydrofolate
↓
Lack of vitamin B12 traps the folate as methyltetrahydrofolate and prevents DNA
synthesis
37.
38.
39.
40. CLINICAL MANIFESTATIONS
Folate deficiency anaemia and Vitamin B12 deficiency anaemia
Serious malabsorption
• Coeliac disease.
• Reduced absorption is seen in Crohn's disease.
Mild thrombocytopenia
The spleen may be slightly enlarged
• Slight fever
Mild jaundice may be present due to the increased breakdown of
haemoglobin found in the abnormal red cells.
41. • Patients notice a tingling in their feet and a loss of vibration sense.
• Occasionally, patients have muscle weakness, difficulty in walking
or experience frequent falls.
• Shortness of breath
• Abnormal paleness of the skin
• Glossitis (swollen tongue)
• Diarrhoea, Nausea, Fast heartbeat
42. COMPLICATIONS
COMPLICATIONS OF VIT B 12 DEFICIENCY
Neurological changes
• Vision problems, Memory loss
• Loss of physical coordination which can affect whole body and cause
difficulty speaking or walking.
• Damage to parts of the nervous system, particularly in the legs
• Vit B12 deficiency lead to temporary infertility (an ability to conceive).
• Stomach Cancer
• Neural tube defects: For pregnant women not having enough vit B12 can
increase the risk of developing a serious birth defect known as neural tube
defect.
• Neural tube is a narrow channel that eventually forms the brain and
spinal cord.
43. TREATMENT
• Hydroxycobalamin as intramuscular injection 1000 μg for 3 weeks
and oral folic acid 5 mg tablets daily for 4 months.
• Blood transfusion should be avoided since it may cause circulatory
overload.
• Diuretics may also need to be given, especially if the patient has
congestive heart failure.
• Potassium supplements may be needed in the elderly and patients
receiving diuretics or digoxin.
44. PERNICIOUS ANAEMIA
• Pernicious anaemia is a specific autoimmune disease that causes
malabsorption of vitamin B12 due to a lack of intrinsic factor.
• Pernicious anaemia is usually a disease of the elderly, the average
patient presenting at 60 years of age.
45. CLINICAL MANISFESTATIONS
• Mainly due to vitamin B12 deficiency.
Include:
• Anaemia, glossitis, neurological abnormalities (neuropathy,
subacute combined degeneration of the spinal cord, retrobulbar
neuritis(inflammation of optic nerve)
• Gastrointestinal manifestations (diarrhoea, anorexia, weight loss,
dyspepsia), hepato splenomegaly, congestive heart failure and
haemorrhagic manifestations.
• Other autoimmune diseases such as autoimmune thyroiditis may be
associated.
47. • Sickle cell syndromes, which can be divided
into sickle cell trait (SCT) and sickle cell
disease (SCD), are hereditary conditions
characterized by the presence of sickle
hemoglobin (HbS) in red blood cells (RBCs).
• SCT is the heterozygous inheritance of one
normal β-globin gene producing hemoglobin A
(HbA) and one sickle gene producing HbS (HbAS)
gene.
• Individuals with SCT are asymptomatic.
• SCD can be of homozygous or compounded
heterozygous inheritance.
• Homozygous HbS (HbSS) has historically been
referred to as sickle cell anemia (SCA).
48. AETIOLOGY
• HbAA- normal person
• HbAS- sickle cell trait (they have a normal life span)
• HbSS- sickle cell disease/anemia
• The sickle cell gene is passed from generation to generation in a
pattern of inheritance called autosomal recessive inheritance.
• This means both mother and father must pass on the defective form
of the gene for a child to be affected.
• If only one parent passes the sickle cell gene to the child, the child
will have sickle cell trait.
• With one normal Hb gene and one defective form of the gene, people
having sickle cell trait make both normal Hb and sickle cell Hb.
49. TYPES
• The four main types of sickle cell anemia are caused by different
mutations in these genes.
• Hemoglobin SS disease
• Hemoglobin SB+ (beta) thalassemia
• Hemoglobin SB 0 (Beta-zero) thalassemia
• Hemoglobin SD, hemoglobin SE, and hemoglobin SO
50. PATHOPHYSIOLOGY
• A mutation in the HBB gene is the cause behind development of sickle
cell anaemia.
• Hb consists of four protein subunits, typically, two alpha-globin and two
beta-globin subunits.
• The HBB gene provides instructions for making beta-globin.
• Abnormal versions of beta globin includes haemoglobin S (HbS),
haemoglobin C (HbC), and haemoglobin E (HbE).
• In people with sickle cell disease, at least one of the beta-globin subunits
in Hb is replaced with haemoglobin S.
51.
52. • In sickle cell anaemia, haemoglobin S replaces both beta-globin
subunits in haemoglobin.
• Basic genetic defect is the single point - there is substitution of
valine for glutamic acid at 6-residue position of Beta globin.
• The membrane of red blood cells containing HbS is damaged,
leading to intracellular dehydration.
• During deoxygenation, red blood cells containing HbS change from
biconcave disc shape to an elongated crescent shaped or sickle
shaped cell. This process is called sickling.
53. • The mechanism responsible for sickling upon deoxygenation of
HbS containing red cells is the polymerisation of deoxygenated HbS
which aggregated to form elongated rod like polymers.
• These elongated fibres align and distort the red cell into classic
sickle shape.
• The oxygen dependent sickling process is usually reversible.
However, damage to red cell membrane leads to formation of
irreversible sickled red cells.
54.
55. SIGNS AND SYMPTOMS
• Patients with severe variants of the disease have chronic anaemia,
arthralgia, anorexia, fatigue and splenomegaly.
• A crisis can be precipitated by infection and fever, dehydration,
hypoxia or acidosis.
• Infarction of the long bones and larger joints or an infarction of a large
organ, for example, the liver, lungs or brain, may all occur.
• Severe pain is a common feature, depending on the site of the
infarction. Destructive bone and joint problems are frequently seen.
56. COMPLICATIONS
• Stroke: occurs if sickle cells block blood flow to an area of brain.
• Acute chest syndrome: this causes chest pain, fever, difficulty breathing.
It can be caused by a lung infection or by sickle cells blocking blood
vessels in lungs.
• Pulmonary hypertension: people with SCA can develop high blood
pressure in their lungs
• Organ damage: blood is having low oxygen so chronic deprivation of
oxygen rich blood can damage nerves and organs, including kidneys, liver
and spleen.
• Blindness: block tiny blood vessels that supply blood to eyes and leads to
blindness.
• Priapism: sickle cells block blood vessels in the penis and leads to
impotence, painful and long lasting erections.
57. TREATMENT
• Prophylactic antibiotics: Penicillin V 250 mg twice a day is usual for
adults with erythromycin prescribed for patients allergic to penicillin.
• Administration of pneumococcal vaccine and Haemophilus
influenzae vaccine is now common.
• Folic acid is commonly used because of the high turn over of red
cells.
• Hydroxycarbamide is effective and may reduce the frequency of
crises
• Strong opioids are required for pain relief. Morphine is a more logical
choice of opioid and has been successfully used in patientcontrolled
analgesia systems.
59. INTRODUCTION
• Thalassemia is a genetic blood disorder inherited from a person’s
parents which is characterised by less and abnormal haemoglobin
production and anaemia.
• Other problems like an enlarged spleen, yellowish skin, and dark
urine can also exist with thalassemia.
• There are two main types, alpha thalassemia and beta thalassemia.
• Severity of alpha and beta thalassemia depends on how many of
the four genes for alpha globin or two genes for beta globin are
missing.
60. TYPES OF THALASSEMIA
• On the basis of gene involved and the subunit of Hb affected it can be
divided into following types:
A. Alpha thalassemia
B. Beta thalassemia
C. Beta thalassemia major
D. Beta thalassemia intermedia
E. Beta thalassemia minor
F. Delta thalassemia
61. CAUSES
• Thalassemia is caused by mutations in the DNA of cells that
make haemoglobin.
• The mutations associated with thalassemia are passed from
parents to children
62. PATHOPHYSIOLOGY
• Normally, the majority of adult hemoglobin (HbA) is composed of
four protein chains, two α and two β globin chains. In thalassemia,
patients have defects in either the α or β globin chain, causing
production of abnormal red blood cells (In sickle-cell disease, the
mutation is specific to β globin).
• The thalassemias are classified according to which chain of the
hemoglobin molecule is affected. In α-thalassemias, production of
the α-globin chain is affected, while in β-thalassemia, production of
the β globin chain is affected.
63. • The β-globin chains are encoded by a single gene on chromosome 11;
α-globin chains are encoded by two closely linked genes on
chromosome 16. Thus, in a normal person with two copies of each
chromosome, two loci encode the β-chain, and four loci encode the α-
chain.
• Deletion of one of the α loci has a high prevalence in people of African
or Asian descent, making them more likely to develop α-thalassemia.
• β-Thalassemias are not only common in Africans, but also in Greeks
and Italians.
64. Alpha Thalassemia: PATHOPHYSIOLOGY
• α-thalassaemias are disorders in which there is defective synthesis of α
globin chains resulting in depressed production of haemoglobins that
contain α-chains i.e. HbA, HbA2 and HbF.
• The α- thalassaemias are most commonly due to deletion of one or more
of the α-chain genes located on short arm of chromosome.
• Since there is a pair of α-chain genes, the clinical manifestations of α
thalassaemia depend upon the number of genes deleted.
• Accordingly, α-thalassaemias are classified into 4 types:
1. Four α-gene deletion: Hb Bart’s hydrops foetalis.
2. Three α-gene deletion: HbH disease.
3. Two α-gene deletion: α-thalassaemia trait.
4. One α-gene deletion: α-thalassaemia trait (carrier).
65. Beta Thalassemia PATHOPHYSIOLOGY
• β-thalassaemias are caused by decreased rate of β-chain synthesis
resulting in reduced formation of HbA in the red cells.
• Instead, most of β-thalassaemias arise from different types of
mutations of β−globin gene.
• The symbol β° is used to indicate the complete absence of β-
globin chain synthesis while β+ denotes partial synthesis of the β-
globin chains.
66.
67. • Transcription defect: Mutation affecting transcriptional promoter
sequence causing reduced synthesis of β-globin chain. Hence the result
is partially preserved synthesis i.e. β+ thalassaemia.
• Translation defect: Mutation in the coding sequence causing stop
codon (chain termination) interrupting β-globin messenger RNA. This
would result in no synthesis of β-globin chain i.e. β° thalassaemia.
• mRNA splicing defect: Mutation leads to defective mRNA processing
forming abnormal mRNA that is degraded in the nucleus.
• Depending upon the extent of reduction in β-chain synthesis, there are
3 types of β-thalassaemia:
• Homozygous form: β-Thalassaemia major
• β-Thalassaemia intermedia
• Heterozygous form: β-Thalassaemia minor (trait)
68. SIGNS AND SYMPTOMS
• Thalassemia disrupts the normal production of haemoglobin and
healthy read blood cells. This causes anaemia.
• With anaemia, blood doesn’t have enough red blood cells to carry
oxygen to tissues resulting in fatiguness.
• Weakness
• Pale or yellowish skin, facial bone deformities
• Slow growth
• Abdominal swelling
• Dark urine.
69. COMPLICATIONS
• Infection
• Iron overload: Excessive iron gets deposited in various organs causing
damage to organs.
• Bone deformities: Causes expansion of bone marrow in widening of
bones. This cause abnormal bone structure, making bones thin and brittle.
• Enlarged spleen: Splenomegaly can make anaemia worse, it reduces life
of RBCs
• Slowed growth rates: May cause decrease in child growth. Puberty may
also get delayed in children with thalassemia.
• Heart problems: Disease such as CHF and Arrythmia may be associated
• with thalassemia.
70. TREATMENT
• Splenectomy helps some patients, and allogeneic stem cell transplant
is used in severe cases.
• Blood transfusions, folic acid supplements, and bone marrow
transplant can be used for the treatment of thalassemia.
• Prevention and treatment of iron overload is done by chelation
therapy (desferrioxamine). Oral chelation with kelfer or deferiprone is
also available now.
72. INTRODUCTION
• The anaemia which involves the genetic or hereditary factors is as
follows:
• Sickle cell anaemia
• Thalassemia
• Congenital pernicious anaemia
• Fanconi anaemia
• Hereditary spherocytosis
• Thrombotic thrombocytopenic purpura
• This is characterised by an inability to produce intrinsic factor which
causes absorption of Vitamin B12.
73. Sickle-cell anaemia
• People with sickle-cell anemia have a gene that causes the blood
protein hemoglobin to form abnormally. As a result, red blood cells
are produced in a sickle shape.
• “This can cause painful episodes called crises, and even strokes and
heart attacks.
• People with sickle-cell anemia may also experience swelling in the
hands and feet and a reduced ability to fight infection.
74. Thalassemia
• Thalassemia occurs when your body is unable to produce enough
hemoglobin, which functions to carry oxygen throughout the body.
This condition is also caused by faulty genes.
• People with mild thalassemia often experience nothing more than the
typical symptoms of anemia, such as tiredness, while those with a
moderate or severe form may have an enlarged spleen, slowed growth,
bone problems, and jaundice.
75. Congenital pernicious anaemia
• This rare type of anemia results when a person is born with an inability
to produce intrinsic factor, a protein in the stomach that helps the body
absorb vitamin B12.
• Without vitamin B12, the body cannot make enough healthy red blood
cells, causing you to become anemic.
• The lack of vitamin B12 can lead to other complications, like nerve
damage, memory loss, and an enlarged liver. Like other forms of
pernicious anemia, this condition is usually treated with vitamin B12
supplements, which may need to be taken for a lifetime.
76. Fanconi anemia
• This type of anemia stems from an inherited blood disorder that
prevents the bone marrow from producing an adequate supply of new
blood cells for the body.
• Besides having the classic signs of anemia, such as fatigue and
dizziness, some people with Fanconi anemia are also at greater risk for
infection because their bodies don’t produce enough white blood cells
to fight germs.
• Some patients are also at greater risk for acute myeloid leukemia, a
type of blood cancer, because their bone marrow makes a large number
of immature white blood cells, preventing the production of normal
blood cells.
77. Hereditary spherocytosis.
• This disease, which is usually passed from parent to child through the
genes, is characterized by abnormal red blood cells called spherocytes
that are thin and fragile.
• These cells cannot change shape to pass through certain organs as normal
red blood cells do, so they stay in the spleen longer, where they are
eventually destroyed. The destruction of the red blood cells causes
anemia.
• Most people with hereditary spherocytosis have only mild anemia, but
stresses on the body from infection can cause jaundice and even a
temporary halt in the bone marrow’s production of blood cells.
78. Thrombotic thrombocytopenic purpura
• Known as TTP for short, this anemia-causing condition results from
a certain faulty blood-clotting enzyme, leading to the clumping of
platelets, which are blood cells that help heal wounds.
• When platelets clump together, fewer platelets are circulating
throughout the body, so people with TTP can experience prolonged
bleeding internally, externally, or under the skin. “It can result in
anemia by affecting red blood cells once they get out of the bone
marrow, causing breakages of those red blood cells in the blood,”.
This is known as hemolytic anemia.
80. • Hemophilia is an inherited bleeding disorder in which a person lacks
or has low levels of “clotting factors”. And as a result, the blood does
not clot properly which leads to excessive bleeding.
• People with hemophilia can experience spontaneous or internal
bleeding and often have painful, swollen joints due to bleeding into
the joints. This rare but serious condition can have life threatening
complications.
81.
82. TYPES
• The three forms of hemophilia are hemophilia A, B and C, and these are
according to which clotting factor is deficient:
• Hemophilia A: Hemophilia A is the most common type of hemophilia,
and it is caused by a deficiency in factor VIII.
• Hemophilia B: Hemophilia B is also called Christmas disease, which is
caused by a deficiency of factor IX.
• Hemophilia C: Hemophilia C is a mild form of the disease caused by a
deficiency of factor XI.
• In extremely rare cases, hemophilia can develop after birth called
“acquired hemophilia”.
• This is the case in people whose immune system forms antibodies that
attack factors VIII or IX
83. CAUSES
Mutations
• Caused by a genetic mutation. The mutations involve genes that code
for proteins that are essential in the blood clotting process.
• Haemophilia A is caused by a mutation in the gene for factor VIII, so
there is deficiency of this clotting factor. Haemophilia B (also called
Christmas disease) results from a deficiency of factor IX due to a
mutation in the corresponding gene.
• A condition referred to as haemophilia C involves a deficiency of
clotting factor XI.
84. CAUSES
Family history
• There are several types of haemophilia, and most forms are inherited.
However, about 30 % people have no family history of the disorder. In this,
unexpected change occurs in one genes associated with haemophilia.
Autoimmunity
• Acquired haemophilia is a rare variety of the condition that occurs when a
person’s immune system attacks clotting factors in the blood. It can be
associated with: Pregnancy, Autoimmune conditions, Cancer and Multiple
Sclerosis.
85. SIGNS AND SYMPTOMS
• The extent of symptoms depends on the severity of clotting factor
deficiency.
• People with a mild deficiency may bleed in the case of trauma.
• People with a severe deficiency may bleed for no reason. This is called
“spontaneous bleeding".
• In children with hemophilia, these symptoms may occur around age 2.
• Spontaneous bleeding can cause the following:
• Unexplained and excessive bleeding from cuts or injuries, or after
surgery or dental work Many large or deep bruises
86. Unusual bleeding after vaccinations
• Pain, swelling or tightness in joints
• Blood in urine or stool
• Nosebleeds without a known cause
• In infants, unexplained irritability
• Emergency signs and symptoms of hemophilia include:
• Sudden pain, swelling and warmth in large joints, such as knees, elbows, hips
and shoulders, and in arm and leg muscles
• Bleeding from an injury, especially in severe form of hemophilia
• Painful, prolonged headache
• Repeated vomiting
• Extreme fatigue
• Neck pain
• Double vision
87. PATHOPHYSIOLOGY
• Haemophilia occurs because of a defect in one of the clotting factor
genes on the X chromosome.
• Haemophilia tends to occur in males, since the gene can be passed
from mother to son.
• Haemophilia A and B are inherited in an X-linked recessive genetic
pattern and are therefore much more common in males. This pattern of
inheritance means that a given gene on the X chromosome expresses
itself only when there is no normal gene present.
• Males lack a second X chromosomes so they are unable to recover for
the defective genes.
88. PATHOPHYSIOLOGY
• Females may become carriers of haemophilia, but they are unlikely to
have the disorder.
• Sometimes, haemophilia is acquired because of a spontaneous genetic
mutation.
• This disorder can also develop if the body forms antibodies to clotting
factors in the blood that then stop the clotting factors from working.
89. COMPLICATIONS
• Deep internal bleeding: Bleeding that occurs in deep muscle can
cause limbs to swell. The swelling may press on nerves and lead to
numbness or pain.
• Damage to joints: Internal bleeding may also put pressure on joints,
causing severe pain. Left untreated, frequent internal bleeding may
cause arthritis or destruction of the joint.
• Infection: People with hemophilia are likelier to have blood
transfusions, increasing their risk of receiving contaminated blood
products.
90. COMPLICATIONS
• Adverse reaction to clotting factor treatment: In some people with
hemophilia, the immune system has a negative reaction to the
clotting factors used to treat bleeding.
• When this happens, the immune system develops proteins (known
as inhibitors) that inactivate the clotting factors, making treatment
less effective.
91. DIAGNOSIS
• Blood test
The sample is then graded to determine the severity of the factor deficiency:
• Mild hemophilia is indicated by a clotting factor in the plasma between 5
and 40 %.
• Moderate hemophilia is indicated by a clotting factor in the plasma
between 1 and 5 %.
• Severe hemophilia is indicated by a clotting factor in the plasma of less
than 1 %.
92. TREATMENT
• There is no cure for hemophilia, most people with the disease can
lead fairly normal lives.
• Slow injection of the hormone desmopressin (DDAVP) into a vein
can stimulate a release of more clotting factor to stop bleeding.
• Plasma infusions are needed to stop bleeding episodes.
• Antifibrinolytics help prevent clots from breaking down.
• Fibrin sealants can be applied directly to wound sites to promote
clotting and healing. Fibrin sealants are especially useful in dental
therapy.
93. TREATMENT
• Physical therapy: It can reduce signs and symptoms if internal
bleeding has damaged joints. If internal bleeding has caused
severe damage, may need surgery.
• First aid for minor cuts: Using pressure and a bandage will
generally take care of the bleeding. For small areas of bleeding
beneath the skin, use an ice pack. Ice pops can be used to slow
down minor bleeding in the mouth.
