Haemoglobinopathies

1. HAEMOGLOBINOPATHIES
HAEMOGLOBINOPATHIES
DR. NEHA

2. TOPICS
 Definition and history
 Prevalence
 Pathophysiology- 1.Sickle Cell Anaemia
2.Thalassemia syndromes
 Haemoglobin Electrophoresis
 Treatment

3. DEFINITION
 Haemoglobinopathies are a group of genetic
disorders caused by production of structurally
abnormal hemoglobin molecule , synthesis of
insufficient quantities of normal hemoglobin , or,
rarely both.
 Sickle cell anemia (Hb S )(Qualitative defect)
 Thalassemias (Quantitative defect)

4. HISTORY
Dr. James Herrick

6.  Dr Vernon Mason
 SICKLE CELL
ANEMIA

9. PATHOPHYSIOLOGY
 SS cells may look normal
when fully oxygenated ;
sickling occurs when O
decreased.
 Other causes of sickling
include decrease in pH and
dehydration of patient.
 Cells become rigid , impeding
blood flow to tissues. Tissue
death , organ infarction and
pain results.
 Sickling is reversible upto a
point.
 Have both extravascular
hemolysis and intravascular
hemolysis.

11. PREVALENCE

14. CLASSIFICATION

16. SICKLE CELL ANEMIA

17. CLINICAL MANIFESTATIONS
Ø Fever and bacteremia- it is a medical emergency ,
requiring prompt medical evaluation and delivery
of antibiotics– 3rd gen Cephalosporin.
Ø Dactylitis (hand foot syndrome )is first
manifestation of pain in children , ocurring in 50%
of children by 2nd yr. --- pain medications whereas
osteomyelitis requires 4-6weeks of antibiotics.

18. Ø Splenic sequestration---early intervention and
maintainence of hemodynamic stability using
isotonic saline or blood transfusion.
Ø Pain- most commonly in chest, abdomen or
extremities, caused d/t tissue ischemia in
microvasculature .
Ø Lung diseases- 2nd m/c cause of hospital
admission.– acute chest syndrome.

19. OTHER COMPLICATIONS
Ø Kidney disease
Ø Psychological complications
Ø Neurological complications
Ø Priaprism

20.  There are 3 types of crisis
1. Aplastic crisis- associated with infections which
causes temporary suppression of erythropoises.
2. Hemolytic crisis- results in exaggerated anemia.
3. Vaso-occlusive crisis- associated with severe
pain. Hallmark symptom of sickle cell anemia.

21. CLINICAL MANIFESTATIONS
 Infants with sickle cell anemia have abnormal
immune functions and , as early as 6 months of
age, may have functional asplenia.- all by 5 yrs.
 Bacterial sepsis is one of the greatest causes for
morbidity and mortality in this patient
population.


22.  Regardless of age , all patients with sickle cell
anemia are at increased risk of infection and
death from bacterial infection , particularly
encapsulated such as streptococcus pneumoniae
and hemophilus influenzae type b.

23. TREATMENT
Ø Blood transfusion
Ø Supplemental oxygen
Ø Emperical antibiotics
(cephalosporins and
macrolides)
Ø Bronchodilators and
steroids for patients
with asthma.
Ø Optimum pain control
and fluid management.

24. ELECTROPHORESIS
 Electrophoresis is a
comprehensive term that
refers to migration of
charged solutes or
particles of any size in a
liquid medium under the
influence of electric field.
 Tiselius was awarded a
nobel prize in 1948 for his
work on protein separation
by electrophoresis.

25. ELECTROPHORESIS

27. PREVENTIVE CARE
Ø All children require prophylaxis with penicillin or
amoxicillin upto 5 years.
Ø Immunization with pneumococcal ,
meningococcal and hemophilus influenza B
vaccine.
Ø Lifelong folate supplementation
Ø Regularly screening for development of gallstones.
Ø Genetic counselling and testing should be offered
to family.

30. METHEMOGLOBINEMIA
 Normal hemoglobin can be oxidised to
methemoglobin.
 It occurs because of either increased production
of oxidised hemoglobin because of exposure to
enviromental agents or diminished reduction of
of oxidised hemoglobin because of underlying
germ line mutations.

31.  Toxic methhemoglobinemia-sulfonamides, lidocaine
and other aniline derivates, and nitrites. -----
Treatment- 1-2 mg/KgBw of methylene blue I/V , over
a period of 5 mins
 Cytochrome b5 reductase deficiency
 Hereditary methhemoglobinemia can be treated by
ascorbic acid 300-600mg daily divided into 3-4 doses.

34. TYPES OF THALASSEMIAS
Ø Alpha thalassemia silent alpha
thalassemia trait hemoglobin H
disease alpha thalassemia
Major(Hydrops fetalis)
Ø beta thalassemia minor beta thalassemia
intermedia beta thalassemia major .

37. HEMOGLOBIN BART’S HYDROPS
FETALIS
Ø Most severe form .
Ø Incompatible with life
Ø Having no functioning
alpha gene.(--/--)
Ø Baby born with hydrops
fetalis , is edematous
and shows ascitis
caused by accumulation
serous fluid in fetal
tissues as a result of
severe anemia.
Ø Hepatosplenomegaly
and cardiomegaly.

39. BETA THALASSEMIA MAJOR
Ø Characterized by
microcytic
hypochromic anemia
with extreme
poikilocytosis .
Ø Detected early in
childhood– failure to
thrive, pale, jaundice,
abdominal
enlargement and
hepatospenomegaly.
Ø Hb level- 4-8g/dl

40. Ø Severe anemia causes
marked bone changes
due to expansion of
marrow space for
increased
erythropoieses.
Ø Failure to thrive and
die young are 2
hallmarks.

41. COMPLICATIONS

42. MANAGEMENT
Ø Hematopoietic stem cell transplantation.
Ø Blood transfusion
Ø Chelation therapy
The optimal time to start chelation is 1-2 years
post transfusion (ferritin level- 1000-1500μg/L)---
- deferoxime , deferiprone
Ø Hydroxyurea-
15-20mg/kg/day used to increase HbF production
and reduce the need for transfusion support.