3. Normal hemoglobins are tetramers of two
α-like and two β-like globin polypeptide
chains.
α-chain: 141 amino acids ( chromosome
16)
β-chain: 146 amino acids ( chromosome
11)
4. CLASSIFICATION
Structural hemoglobinopathies : hemoglobins with
altered amino acid sequences eg HbS
Thalassemias : defective biosynthesis of globin chains
Thalassemic hemoglobin variants : structurally
abnormal Hb associated with co‐inherited thalassemic
phenotype
a) HbE,
b) Hb Constant Spring,
c) Hb Lepore
Hereditary persistence of fetal hemoglobin
Acquired hemoglobinopathies
A. Methemoglobin
B. Sulfhemoglobin
C. Carboxyhemoglobin
D. HbH in erythroleukemia
5. SICKLE CELL DISEASE
SCD is an inherited chronic hemolytic anemia
whose clinical manifestations arises from
tendency of the hemoglobin to polymerize and
deform red cells into the circulation .
GENETICS
In 6th position in beta globin chain of
hemoglobin VALINE replaces the GLUTAMIC
ACID .
7. EFFECT OF HbS
ON ERYTHROCYTE
A) Membrane damage leading to cellular
dehydration
B) Cells become adherent to vascular
endothelium
C) There will be both intravascular and extra
vascular hemolysis
D) There will be reduced ability of the red cells to
deform .
F) Finally there will be loss of response of vessel
to NO leading to thrombosis ultimately
8.
9. CLINICAL MANIFESTATIONS
Clinical symptoms will vary among people with
SCD.
Usually the symptoms are more severe in people
with HbSS or sickle thalassemia.
ANAEMIA
1) It mainly depends upon the underlying β –
globulin genotype.
2) the baseline hemoglobin will be comparatively low
than normal individuals .
10. ANAEMIA
1) It mainly depends upon the underlying β – globulin
genotype.
2) the baseline hemoglobin will be comparatively low
than normal individuals .
Gradual fall in HB value will be due to varied
causes , like
1) iron def , 2) folic acid / b12 def 3) CRF
An acute fall in HB may be due to
1) APLASTIC CRISIS
2) SPLENIC SEQUESTRATION.
11. APLASTIC CRISIS
Sudden cessation of marrow erythropoiesis
mainly related to PARVO VIRUS B 19 infection
leading to abrupt fall in Hb levels.
Typically presents 5-7 days after exposure.
Clinical features- worsening of symptoms of
anaemia
Blood picture – severe anaemia ,
reticulocytopenia .
Treatment – mainline of management is PRBC
transfussion.
Usually resolves with in 2 weeks
12. SEQUESTRATION CRISIS
Acute sequestration may be characterized by
1) acute exacerbation of anemia. ( drop of Hb >
2gm/dl)
2) reticulocytosis
3) tender enlarging spleen
4) rarely hypovolemia
Treatment is mainly replasing blood volume and
RBC mass.
usually reoccurs in 50 % of cases .
And hence splenectomy is recommended after the
acute event abated.
13. ACUTE PAINFUL SYNDROME ( sickle crisis)
1) It is the most frequent symptom with which
patient present .
Pathology : vaso-occlution of bone marrow leading to
bone infarct.
• More common in young adults than old age.
• Precipitating factor are
1) cold , 2)dehydration , 3) infection ,4) stress
• The diagnosis is mainly based on history and
physical examination.
• TREATMENT -1) adequate analgesia – NSAID (
ketorolac),morphine ,meperidine , acetaminophen ,
naproxen.
• 2) adequate hydration.
15. INFECTIONS
1) Early loss of splenic function leads to increased risk
of infection and sepsis.
Most common infections were
1) Meningitis ( MC; S.pneumoniae)
2) pneumonia ( MC: Mycoplasma and respiratory
virus)
3)osteomylitis ( MC: SALMONELLA )
4) uti
5) sepsis ( MC: Streptococcus )
TREATMENT : Antimicrobial IV therapy has to be
given.
Prophylactic penicillin has to be given
Age < 3 – oral penicilline V 125 mg BID daily
AGE > 3 - oral penicilline V 250 mg BID daily
Pneumococcal , H. influenzae , hepatitis B Vaccination
16. NEUROLOGICAL COMPLICATIONS
1) TIA / STROKE / FOCAL SEIZURE are the
common clinical manifestation of SCD
2) precipitating factors are 1) low HB 2) high TC
3) low HBF 4) high systolic BP.
3) both hemorrhagic stroke and ischemic stroke can
occur
4) SCD patients with neurological complaints has to
be evaluated with CT or MRI as needed .
5) the main line of management in both the type of
stroke is Partial-exchange transfusion .
6) repeated transfusion were done to maintain the
HbS less than 30 % for secondary prevention .
7) Transcranial doppler ultrasound ( TCD) was
used as an effective tool in screening to detect
stenosis in asymptomatic patients.
ROLE OF ASPIRIN IS STILL UNDER EVALUATION
FOR SECONDARY PREVENTION OF ISCHEMIC
20. SICKLE CELL TRAIT
HbS <50%, HbA >50%
Normal life span with very rare
complications.
Complications include sudden death during
exercise, splenic infarcts at high altitude,
hematuria, hyposthenuria, bacteriuria, renal
medullary carcinoma.
No restriction on activities.
21. DIAGNOSIS
SCREENING
1) PERIPHERAL SMEAR.
Sickle shaped or cigar shaped deformed rbc
average reticulocyte count is 10 %
platelet count and white blood count may also be
increased.
howell-jolly bodies may be present.
2) SICKLING TEST : sickling of RBC can be induced
by adding a drop of blood with sodium metabisulfite.
23. DISEASE MODIFIERS
HYDROXYCARBAMIDE - Used in SCD patients
with severe clinical manifestations .
1)It increases the concentration of HBF.
2)Its use had effectively reduced the painful
episodes and acute chest syndrome.
3)Dose = 20 mg/kg / day to a max of
2000mg/day
4)Adverse effect – myelosuppression .
5) Decitabine is used to improve HBF levels in
patients not responding to hydroxycarbamide
24. EXCHANGE TRANSFUSION - Severe acute
vaso-occlusive crisis , intractable pain , stroke ,
priapism and acute chest syndrome .
ALLOGENEIG HEMATOPOIETIC STEM CELL
TRANSPLANTATION is performed as a curative
procedure.
GENE THERAPY .
25.
26. THALASSAEMIA are group of disorder with a
genetically determined reduction in the rate of
synthesis of one or more types of normal
hemoglobin polypeptide chain .
Thalassemia is an inherited autosomal recessive blood
disorder.
27. BETA THALASSAEMIAS
A genetic mutation in beta thalassaemia leads to
reduced production of beta chain with raised
alpha chain and a subsequent decreased
amount of HB A .
Beta globin synthesis is controlled by one
gene on each chromosome 11
28. • Alpha thalassemia is the result of deficient or absent
synthesis of alpha globin chains, leading to excess beta
globin chains.
•Alpha globin chain production is controlled by
two genes on each chromosome 16
Alpha Thalassemia
29. BETA THALASSAEMIA –
PATHOLOGY
In β-thalassemia, there is an excess of α-globin
chains relative to β and α- globin tetramers (α4)
are formed. These inclusions interact with the
red cell membrane and shorten red cell survival,
leading to anemia and increased erythroid
production ( extra medullary hematopoiesis).
The γ-globin chains are produced in increased
amounts, leading to an elevated Hb F (α2γ2).
30.
31. ALPHA THALASSAEMIA
Normal production of alpha chains is absent which
results in excess production of gamma- globin chains
in the fetus and newborn or beta- globin chains in
children and adults.
The β-globin chains are capable of forming
soluble tetramers (beta-4, or HbH)
This form of hemoglobin is still unstable and
precipitates within the cell, forming insoluble
inclusions called Heinz bodies
32.
33. CLINICAL FEATURES
• Anemia
• Marked hepatosplenomegaly
• Marrow hyperplasia frontal bossing & prominent
malar eminence
• Chipmunk facies or thalassemic facies
• Iron overload – cirrhosis , pancreatic haemosiderosis
• Growth retardation
• Delayed puberty
• High output failure
• Gall stones
37. Use of RDW Values in the
Diagnosis of Thalassemia
Microcytic Anemia
Children 6 months ‐6 years of age:
MCV <70fl Children 7 to 12 years of
age: MCV <76fl
↓
RDW
↓ ↓
Normal Elevated (>15)
↓ ↓
Favors Thalassemia Ferritin level
↓ ↓
Normal(>100ng/mL) Low(<10ng/mL)
↓ ↓
Favors Thalassemia Favors Iron
Deficiency
anemia
39. TREATMENT
• Blood transfusion to maintain hematocrit
• Folate supplementation
• Avoid iron therapy
• Desferrioxamine for iron chelation
• Splenectomy
• Allogenic bone marrow transplantation
• Gene therapy
• Antenatal diagnosis of thalassemia syndromes is now
widely available.
• DNA diagnosis is based on PCR amplification of
fetal DNA, obtained by amniocentesis or chorionic
villus biopsy .
40. HAEMOGLOBIN E
It is mainly found in south east part of asia , india,
burma , srilanka .
GENETICS : 26th position in beta chain lysine or
glutamic acid .
TYPES
HbE trait , HbE disease
Clinical features :Patient are mostly asymptomatic ,
may have mild jaundice and anemia .
PAERIPHERAL SMEAR : showing marked
hypochromia , target cells and reduced MCV , MCH .
Usually no treatment is neaded.
But when associated with SCD or THALASSAEMIA
may lead to severe disease
.
41. HAEMOGLOBIN D
Mostly found in north west india , pakistan and
iran.
It was originaly called as HbD LOS ANGLES
GENETICS : 121th position in beta chain
glutamine for glutamic acid .
HbD mobility in electrophoresis cellulose acetate
is identical as HbS .
HbD do not sickle and asymptomatic .
42. ACQUIRED
HEMOGLOBINOPATHIES
METHAEMOGLOBINAEMIA
1) Excess accumulation of methaemoglobin in
red cell.
2) Methaemoglogin lacks capacity to carry
oxygen.
CAUSES :
1) Drugs ( sulphonamides , primaquine , nitrates ,
kcl.)
2) toxin exposure : nitrobenzene and aniline
3) congenital
CLINICAL FEATURES :
Cyanosis , headache , tachycardia , muscular
cramps , weakness ,
43. DIAGNOSIS
chocolate brown colour of blood .
spectroscopic identification of methaemoglobin .
usually clinical : cyanosis with no or little
dyspnea.
Treatment : to remove the cause .
methylene blue 2mg/kg in 1 % aqueous solution.
44. SULPHAEMOGLOBINAEMIA
Abnormal sulphur containing haemoglobin .
does not act as an oxygen carrier .
caused by ingestion of sulphur containing
drugs.
it is irreversible .
clinical feature : cyanosis.
diagnosis : spectroscopy
Treatment is removal of the cause .
