Transcript thalassemia overview

Points to be discussed:
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Definitions
Patho-physiology
Signs & Symptoms
Diagnosis
Options of management.
Complications
Preventive measures
Long term follow up of patients
DEFINITIONS
 THALASSEMIA MAJOR
 THALASSEMIA INTERMEDIA
 THALASSEMIA MINOR, TRAIT,
HETEROGENOUS
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An example of inheritance:
Marriage between two carriers
Developmental expression of the globin
chains
 Embryonic hemoglobins
 z2e2
 a2e2
 z2g2
 Fetal hemoglobins
 a2g2 HbF
 Adult hemoglobins
 a2d2 HbA2
 a2b2 HbA
Three Normal Hemoglobins
 Hb A
a 2b 2
96%
 Hb A2
a 2d 2
3%
 Hb F
a 2g 2
1%
b-THALASSAEMIA
An abnormality associated with one b
gene is called b-thal minor (bTm).
An abnormality associated with two b
genes is called b-thal major (bTM).
b chain production may be decreased or
absent resulting in excess free a chains.
If production is decreased we refer to the
phenotype as b+, if absent bo.
HAEMATOLOGICAL PROFILE
B T Minor
Hb
N-Dec
RCC
Inc (Marrow compensating for
ineffective haematopoiesis
MCV
Dec 
MCH
Dec 
Hypochromasia
+
Anisocytosis
++ (Microcytes)
Poikilocytosis
Target Cells+
Immature Forms
Polychromasia Coarse basophilic
stippling
 Mentzer: MCV
--- --- = if <13 thal minor
RBC
>13 then iron deficiency
 Shine - Lal: (MCV)2 X MCH = if
<1530 then thal minor
>1530 then iron deficiency
 England- Frazer : MCV- (Hgb X 5)RBC- 3.4 = if negative : thal minor
positive : iron def
-
Hb. ELECTROPHORESIS
 HbA:
 HbF:
Present
N-Slightly Inc (Only compensating
for 1 chain)
 HbA2: Inc (4-5%, reason unknown but
this feature is used diagnostically
differentiating from bTM or a TM)
b TM
b0b0 – most severe – no b chain
production.
b0b+ - moderately severe – some
b chain production.
b+b+ - Increased HbF with
normal or elevated HbA2 – there
is remained HbA.
Clinical severity
varies
accordingly.
CLINICAL ASPECTS
 Hepatomegaly and splenomegaly.
 Chronic
haemolysis
that
may
be
accompanied by gallstones, gout and icterus
(jaundice).
 Not usually detected until 6 months of age.
 Excess iron from blood transfusions may
lead to cardiac and hepatic problems.
 As with other haemolytic anaemias,
more iron is absorbed from the gut
exacerbating iron overload.
 Largely overcome by the use of
Desferroxamine.
HAEMATOLOGICAL PROFILE
Hb
Anisocytosis
Dec
+++ (Macrocytes,
Microcytes)
Poikilocytosis
Target cells +++
Tear drops
Schistocytosis
Acanthocytes, Howell Jolly
Bodies, Target Cells (post
splenectomy)
Immature Forms
Polychromasia ++
Nucleated RBC +++ (bone
marrow response)
Blood Film - BTM
•
X-RAYS IN THAL. PTs
TRANSFUSIONAL IRON OVERLOAD IN
THALASSEMIA
120
Death
100
Cardiac Failure
Hypoparathyroidism
Iron (g)
80
Hypothyroidism
60
Diabetes
40
Hypogonadism
Cardiac arrhythmia
20
Hepatic Fibrosis --> Cirrhosis
0
1
3
5
7
9
11 13 15 17 19
Age (years)
Thalassemia Centre, Dept. of Pediatrics
University of Turin, Italy
IRON ACCUMULATION IN
TRANSFUSION-DEPENDENT ANEMIAS
Blood Transfusion
0.3-0.5 mg iron/kg/day
In a 50 kg person

15-25 mg/day
Iron
Accumulation
13-24 mg/day
Iron Excretion
(Urine & Feces)
1-2mg/day
Management
 Medical /Nursing management
 Social and Behavioral management
 Management of complications
 Compliance
Medical Management
 Blood Transfusion-----Dr. Khawla
 Chelation Therapy---- Dr Ahmad
 Bone Marrow Transplant
 Gene Therapy
TRANSFUSION CARE OF THE CHILD WITH
THALASSEMIA MAJOR
Red Blood Cell Transfusion:
 Transfusion ≥ Hb 9.0 g/dl
 Extended red cell genotype
 Match donor blood to ABO, rhesus and Kell
 filter or wash blood – (white cell depletion)
 Vaccinate with hepatitis B Pre-tX
Bone Marrow Transplant
 HLA matched Donor
 Preparation of the patient
 Consider selection criteria
 Stem cells could be collected by:

Bone Marrow Aspiration

Peripheral apheresis

Cord Blood
When
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COMPLICATIONS

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

Cardiac
Endocrine
Hepatic
Renal
Skeletal
Virus transmission
Blood reactions.
TRANSFUSIONAL IRON OVERLOAD IN
THALASSEMIA
120
Death
100
Cardiac Failure
Hypoparathyroidism
Iron (g)
80
Hypothyroidism
60
Diabetes
40
Hypogonadism
Cardiac arrhythmia
20
Hepatic Fibrosis --> Cirrhosis
0
1
3
5
7
9
11
13
15
17
19
Age (years)
Thalassemia Centre, Dept. of Pediatrics
University of Turin, Italy
CROSS-SECTIONAL STUDY OF 342 PATIENTS
IN THE NIH-SPONSORED THALASSEMIA CLINICAL
RESEARCH NETWORK REGISTRY*
16-24 yr
(n=93)
25+ yrs
(n=129)
Hypogonadism (req. meds)
Diabetes Mellitus
41%
9%
62%
21%
Thyroid Disease
Hypoparathyroidism
Cardiac Disease (req. meds)
8%
1%
5%
17%
9%
Age Group
23%
(30/128)
Reference: Adapted from Cunningham, et al. Blood. Online Feb. 26, 2004 DOI 10.1182
B-THAL. INTERMEDIA
THALASSEMIA MAJOR – SURVIVAL
Prevention
• Premarietal Screening
• Prenatal diagnosis
• Pre Implantation Genetic
Diagnosis