HEMOGLOBINOPATHIES

GROUPS A (1-33) B (34-67) C (68-100) D (101-134)
Test 1 7.27 7.18 7.22 7.23
Total 7.27 7.18 7.22 7.23
How is the score calculated?
Each question has got 10 points. No negative points.

For ‘n’ number of questions, the average score of an individual is calculated = (Score secured)/n
For each group (of ‘x’ members), the average score is calculated as = (Sum of scores of x members)/x
Case
AVENGERS - end game
HEMOGLOBINOPATHIES
Normal hemoglobins found in adults
Hemoglobinopathies
Quantitative defect Qualitative defect
Globin gene mutations/deletions that Globin gene mutations that result in
result in decreased production of globin structural abnormalities of the globin
chains chain:
• Alpha thalassemia • Hb S, Hb C, Hb E and other Hb
• Beta thalassemia variants
• Unstable Hb, Methemoglobin
SICKLE CELL
DISEASE
Sickle cell disease
A single glutamic acid to valine
substitution at position 6 of the beta
globin polypeptide chain.
It is inherited as an autosomal
recessive trait
Homozygotes only produce abnormal

beta chains that make haemoglobin S
(HbS, termed SS), and this results in the
clinical syndrome of
sickle-cell disease.
Heterozygotes produce a mixture of
normal and abnormal beta chains that
make normal HbA and HbS (termed AS),
and this results in sickle-cell trait.
Individuals with sickle-cell trait are relatively resistant to the lethal effects of falciparum malaria in early
childhood; the high prevalence in equatorial Africa can be explained by the survival advantage it confers
in areas where falciparum malaria is endemic.
Pathophysiology
Painful vaso-occlusive crisis
• Pain: most common clinical complication in SCD
• Microvascular entrapment of red cells, occlusion of capillaries and recruitment of inflammatory mediators.
• Cycles of ischemia and reperfusion.
• Majority of pain episodes are managed by patients at home
• 1/3 of patients have daily pain
• Triggers: cold, dehydration, stress, infection
Key points for management:

• Rapid pain control - IV opioid pain medication: NSAIDs 5-7 days
• Hydration and trasnfusions
• Search for infection, other precipitators
• Emperic antibiotics: 3rd gen cephalosporin, macrolide
• Oxygen if hypoxic
Acute Chest Syndrome
• 2nd most common cause of hospital admissions in SCD

• Leading cause of premature death
• Recurrence rate: 80%
• Diagnosis: Acute pulmonary infiltrate in SCD patient
• Presentation: Fever, chest pain, dyspnea, cough, hypoxia
• Causes
o Pulmonary infection
o Fat embolism
o Pulmonary embolism
Laboratory Diagnosis of SCD
• CBC: low hemoglobin, low hematocrit • Peripheral blood film
• High reticulocyte count –Normochromic, normocytic red blood cells
• Hemolysis markers –Sickle cells
• Peripheral smear –Polychromasia
• Hemoglobin identification: –Few target cells
electrophoresis, HPLC –Howell-Jolly bodies (HJB)
–High white blood cell count
–May see high platelet count
Sickle solubility test
• Simple, inexpensive, widely available
• Polymerization of HbS by adding a reducing agent, precipitation, causing solution to become
turbid.
• Positive for SS or AS, does not identify other Hb variants
Hemoglobin analysis: identify, quantify HbS and variants

–High performance liquid chromatography (HPLC)
–Iso-electric focusing (IEF)
–Gel-electrophoresis
Treatment of SCD
 General medical care  Disease Modifying Therapies
• Vaccinations o Hydroxyurea
o Influenza annually o L-glutamine
o Pneumococcal every 5 years o Crizanlizumab
o Hepatitis A/B o Voxelotor
• Annual eye exam for retinopathy o Transfusions
• Nutrition  Curative Therapies
• Control blood pressure o Stem cell transplantation
o Gene Therapy
 Pain management: Acute and Chronic
 Screen for and manage acute and chronic
complications
 Iron overload management
How to blood transfusions and HbF help?
• A regular transfusion program to
suppress HbS production and maintain
the HbS level below 30% may be
indicated in patients with recurrent A high HbF level inhibits polymerisation of
severe complications, such as HbS and reduces sickling. Patients with
cerebrovascular accidents in children sickle-cell disease and high HbF levels have a
or chest syndromes in adults. mild clinical course with few crises
• Exchange transfusion, in which a
patient is simultaneously venesected
and transfused to replace HbS with
HbA, may be used in life-threatening
crises or to prepare patients for
surgery.
Other abnormal hemoglobins
• Another beta-chain haemoglobinopathy, haemoglobin C (HbC)
disease, is clinically silent but associated with microcytosis and target
cells on the blood film.
• Compound heterozygotes inheriting one HbS gene and one HbC gene
from their parents have haemoglobin SC disease, which behaves like a
mild form of sickle-cell disease.
• SC disease is associated with a reduced frequency of crises but is not
uncommonly associated with complications in pregnancy and
retinopathy.
THALASSEMIAS
General overview
A globin gene disorder
• Most common genetic disorder in the world
• Decreased rate of synthesis of one or more globin chains
• Due to deletion or mutations in globin genes
• Resultant unbalanced chain synthesis
– Ineffective erythropoeiesis:
• Excess of normal globin chains, damage to erythroid precursors
– Hemolytic anemia:
• Damage to mature erythroctyes
Silent carrier
HbH disease
α-Thalassemia trait
Hb Bart

HEMOGLOBINOPATHIES

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GROUPS A (1-33) B (34-67) C (68-100) D (101-134)

Test 1 7.27 7.18 7.22 7.23

Total 7.27 7.18 7.22 7.23

How is the score calculated?

Each question has got 10 points. No negative points.

Homozygotes only produce abnormal

Key points for management:

• 2nd most common cause of hospital admissions in SCD

Hemoglobin analysis: identify, quantify HbS and variants

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