2. Session 1 - Diagnosis of thalassemia - Dr. Akhil Ranjan Biswas.ppt
1. Dr. Akhil Ranjon Biswas
Associate Professor, BMT
Dept. of Hematology
Dhaka Medical College & Hospital
akhil.biswas@yahoo.com
Diagnosis of Thalassemia and Related
Hemoglobin Disorders
8. Pathophysiology of Phenotypic Heterogenecity: A Glimpase
Stable hemoglobin molecule in adult is a tetramer formed of-
2 alpha globin chain, with,
2 beta (Hb A), gamma (Hb F) or delta (Hb A2) globin chain.
Quantitative imbalance between alpha and non-alpha globin chain
are responsible for clinical expression of thalassemia.
10. Present talk will principally cover β
thalassemia and related disorders
11. According to Disease Potential Thalassemias are
1. Symptomatic Thalassemia: Thalassemia Major & Thalassemia
Intermedia
2. Asymptomatic and silent carrier
From here on, term ‘thalassemia’ will be used for symptomatic
thalassemias.
12. Diagnosis of symptomatic thalassemia (Thalassemia Major &
Thalassemia Intermedia) typically relies on
1. Clinical features (symptoms and signs): Few unique but mostly
non-specific
2. Typical lab findings
13. Clinically Popular Features of Thalassemia
1. Moderate to severe pallor/anemia
2. Mild jaundice
3. Splenomegaly
4. Hepatomegaly
5. Stunted growth
6. Typical facial changes: frontal bossing, prominent maxilla and
zygoma, depressed nasal bridge.
7. Poorly developed or undeveloped secondary sexual character
8. Typical radiological finding
14.
15.
16. Most of those popularly known pictures are associated with mostly
irreversibly complicated thalassemia major, certainly destined to
deadly outcome shortly.
For successful and meaningful management of thalassemia we must
be able to diagnose symptomatic thalasemmia before appearance
of those popular picture
So, clinical features of thalassemias to be redefined
17. Clinical features of thalassemia
Clinical features of thalassemia necessarily mean clinical features of
symptomatic thalassemias, namely thalassemia major and
thalassemia intermedia. Though thalassemia major and
intermedia present generally almost similar features but in
significantly different spectrum.
18. Clinical features of thalassemia
Features of thalassemia major
Should present within 2 years of age if addressed properly
Failure to thrive
Repeated infection
Pallor
Splenomegaly (and hepatomegaly if not transfused sufficiently)
May have clinically evidenced jaundice
Regular transfusion required before 2 year of age for normal
growth and development
Bony expansion causing frontal bossing, malar prominence etc
along with growth retardation revealed later in childhood if not
transfused sufficiently.
19. Clinical features of thalassemia
Features of thalassemia intermedia
Very diverse spectrum of expression, in one end it merge with
thalassemia major and on the milder end it merge with thalassemia
minor.
Pallor, splenomegaly etc become clinically evident after 2 year of
age
Heterogeneous clinical expression: some patients require transfusion
since early childhood and some patient may be able to maintain
normal growth and development without any transfusion.
Some patient may present in adulthood with paraplegia due to
extramedullary hemopoiesis in spinal canal, with features related to
iron loading, chronic jaundice, episodic or chronic fatigue etc.
Growth retardation, bone deformity, hepatomegaly only seen in more
20. Laboratory investigation
1. CBC:
1. Hb <9 g/dl
2. MCV - low/variable
3. MCH- low
4. MCHC- low or normal
5. RDW- markedly raised
6. WBC & Plt generally
normal
2. PBF : Gross anisopoikilocytosis,
tear drop cells, target cells,
normoblast, basophilic
stippling etc
21. Laboratory Diagnosis
Hemoglobin electrophoresis:
Common thalassemia genotypes are
Compound heterozygous HbE/ β thalassemia
Double heterozygous/homozygous β thalassemia (β/β thalassemia)
Less common genotypes are
δβ thalassemia compound heterozygote with Hb E or β thalassemia or homozygous
δβ
Hb Lepore/Hb E, Hb Lepore/β, Hb Lepore/Hb Lepore
Hb H disease
*Hb S/β thalassemia is a sickling disorder rather than thalassemia
22. Laboratory Diagnosis: Hb Electrophoresis
β/β thalassemia:
Hb A: 0 to variable
Hb F: >15 to 99%
Hb A2: Variable but <8%
Most likely β thalassemia major
23. Laboratory Diagnosis: Hb Electrophoresis
β/β thalassemia:
Hb A: 0 to variable
Hb F: >15 to 99%
Hb A2: Variable but <8%
Most likely β thalassemia intermedia
24. Laboratory Diagnosis: Hb Electrophoresis
Hb E/β thalassemia:
Hb A: 0 to variable
Hb F: >15 to variable
Hb E: > 40 to variable
Hb A2: Variable but <8%
25. Laboratory Diagnosis: Hb Electrophoresis
Hb E/β thalassemia:
Hb A: 0 to variable
Hb F: >15 to variable
Hb E: > 40 to variable
Hb A2: Variable but <8%
26. β/β thalassemia:
Hb A: 0 to variable
Hb F: >15 to 99%
Hb A2: Variable but <8%
Laboratory Diagnosis: Hb Electrophoresis
δβ/β or δβ/ δβ thalassemia:
Hb A: 0 to variable
Hb F: >15 to 99%
Hb A2: <3%
δβ/β or δβ/ δβ thalassemia: Conditions tricky to diagnose
27. Laboratory Diagnosis: Hb Electrophoresis
•26 year old lady
•Height 160 cm
•Well developed 2ndary sexual character
•Occasional transfusion requirement
•Hb 7.5 gm/dl with typical PBF of
thalassemia
Diagnosis?
28. Laboratory Diagnosis: Hb Electrophoresis
This type of electrophoretic
pattern with thalassemia
intermedia like clinical
expression suggest δβ/β or
δβ/ δβ thalassemia
29. Laboratory Diagnosis: Hb Electrophoresis
Significant aberration from classical electrophoretic pattern is not
uncommon.
So, electrophoresis pattern should always be interpreted in the
context of clinical features, PBF and transfusion history.
Parent screening may be needed in some cases.
30. Laboratory Diagnosis: Additional
Serum bilirubin: total (raised but not >5 mg/dl), direct (normal
unless complicated) & indirect (raised)
Retculocyte count: relative reticulocytopenia
Serum ferritin: usually raised
*Lot more investigations are related to management issues and to be
discussed in relevant sections
31. Carrier Detection
• Detection of asymptomatic/silent carriers are primarily driven by CBC and
almost certainly confirmed by Hb Electrophoresis (capillary preferred)
• There are some other cheaper and easily accessible methods those are
less specific and sensitive
• Relevant types in Bangladesh are
• Hb E trait
• β thalassemia trait
• Homozygous Hb E (Hb E disease)
• δβ thalassemia trait
• Hb Lepore trait
* α thalassemia traits can’t be diagnosed but suspected from blood picture and electrophoresis.
32. •Apparently Healthy
•Age >12 year
•No red cell transfusion in preceding 4 month
CBC MCV <78 fl or MCH <27 pg
Capillary
Hemoglobin
Electrophor
esis
A2 >3.7%
F <5%
A= Rest
A2+E >12%
F <1%
A= Rest
Hb A= 0%
Hb F= <5%
A2+E= Rest
A2 <3.2
F= 5-20%
A=Rest
A2 <3.3
F <1
A= Rest
(Normal pattern)
Other
patterns
MCV <72fl + Normal MCHC
Hb E trait β
thalasse
mia trait
Homozygous
Hb E (Hb E
disease)
δβ
thalassemia
trait
Probable α thal
trait when iron
deficiency is
excluded
Expert Consultation
34. Mentzer index ≤12 is most specific but not very sensitive
predictor of thalassemia minor
Mentzer Index = MCV÷ RBC (million/cmm)
MCV cut off value <72 fl is the most sensitive but very unspecific
predictor of thalassemia minor
35. Red cell indices in thalassemia minor
Mentzer index = 12 Mentzer index = 10
