Non transfusion dependent thalassemia

1
,

• Non Transfusion Dependent Thalassemia
• (NTDT)
• Thalassemia from genetic disease to clinical
  diagnosis
• Anwer Ghani
• FIBMS
• iRAQ

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Non-transfusion-dependent thalassemia (NTDT) is a
term used to describe thalassemia phenotypes that
do not depend on regular blood transfusions for
survival and daily function.
3
NTDT phenotypes include patients with
ß-thalassemia intermedia, hemoglobin
E/ß-thalassemia, and Hemoglobin H disease
(a-thalassemia intermedia) but also those with
structural variant of hemoglobin associated with
a or ß thalassemia in heterozygous condition
which often have analogous characteristics.
4
Non-transfusion-dependent thalassemia (NTDT) is a
broad term encompassing patients who do not
require lifelong transfusion therapy for
survival.
5
NTDT patients commonly, present to medical care
later in childhood and with milder anemia and
clinical symptoms compared to patients with
transfusion-dependent forms.
6
In NTDT, iron overload is likely mediated by a
variety of factors, including increased
erythropoiesis, hypoxia and the contribution of
factors such as erythroferrone, which suppresses
hepcidin synthesis in the liver.
7
Because hepcidin functionally inhibits iron
egress from cells by binding and internalizing
the iron transporter ferroportin in enterocytes,
iron absorption is increased under conditions of
reduced hepcidin synthesis.
8
In hypoxic conditions, synthesis of molecules
responsible for mediating iron absorption
(including ferroportin) are increased in the
duodenum, further contributing to the iron
overload in NTDT.
9
Presentation of NTDT may include mild to severe
anaemia, enlarged spleen and/or liver, skeletal
deformities, growth retardation, elevated serum
ferritin and iron overload.
10
The contributing factors to disease progression
are ineffective erythropoiesis and increased
haemolysis, which lead to chronic anaemia.
11
The body's attempts to correct the anaemia result
in constantly activated erythropoiesis, leading
to marrow expansion and extramedullary
haematopoiesis.
12
Diagnosis of NTDT is largely clinical.
13
NTDT patients are at risk of developing a wide
variety of clinical complications including
gallstones, leg ulcers, growth retardation,
pulmonary hypertension (PHT), splenomegaly, liver
disease and thromboembolic events.
14
Many of the clinical complications common in NTDT
can be prevented by early intervention
strategies.
15
A diagnosis of NTDT before the onset of clinical
complications is therefore a valuable investment
in the future health of patients.
16
NTDT patients with moderately severe phenotype
can develop a haemolytic crisis during an acute
pathogenic infection or high fever.
17
The Hb levels of NTDT patients experiencing a
haemolytic crisis rapidly decline and as a result
they can be mistaken for having TDT and
erroneously entered into a management programme
of lifelong, regular transfusions.
18
Clinical symptoms such as clinical anaemia,
fatigue, lethargy, poor feeding, poor weight
gain, intercurrent infection, liver and spleen
size and development of bone deformities. These
parameters will be carefully considered to
categorize patients into either TDT or NTDT
phenotypes.
19
However, even though NTDT can be defined by
genotype, the diagnosis is mainly clinical and it
is based on the severity of the patient's
condition.
20
Taher et al. have suggested raising baseline Hb
for NTDT patients to over 9 µg/dL in order to
prevent future complications as a prophylactic
measure.
21
It is known that NTDT patients develop extensive
liver iron loading although their serum ferritin
levels are relatively low compared with the serum
ferritin levels indicative of liver iron loading
in transfusion-dependent patients .This
complicates the monitoring of physiological iron
loads in NTDT, because the current thresholds for
serum ferritin used to guide chelation therapy in
transfusion-dependent patients cannot be
extrapolated to NTDT patients.
22
Management of NTDT is based on managing symptoms.
23
Management of NTDT includes blood transfusions,
hydroxyurea treatment, iron chelation and
sometimes splenectomy.
24
Minihepcidins or agents that induce hepcidin
expression in Hbbth3/ mice decreased transferrin
saturation, heme synthesis, hemichrome formation,
and improved RBC lifespan, anemia, and
splenomegaly.
25
Prognosis for well managed patients is good, with
most patients living a normal life.
26
In NTDT, effective iron chelation can keep serum
ferritin levels relatively low, thereby
preventing the development of clinical
complications due to iron overload.
27
In conclusion, luspatercept treatment) Reblozyl)
improved quality of life and RBC transfusion
burden compared with placebo in patients with
NTDT in the BEYOND trial, Dr Kattamis said in a
presentation accompanying his research teams
poster.
28
Reference 1-Published 30 Vip Viprakasit, Paul
Tyan, Sarayuth Rodmai Ali T Taher
Identification and key management of
non-transfusion-dependent thalassaemia patients
not a rare but potentially under-recognised
condition. September 2014. Orphanet Journal of
Rare Diseases volume 9, Article number 131
(2014). 2- Paolo Ricchi,1 Aldo Filosa,1 Aurelio
Maggio,2 and Suthat Fucharoen3
Non-Transfusion-Dependent Thalassemia A Complex
Mix of Genetic Entities Yet to Be Fully
Discovered. Hindawi Volume 2015 Article ID
161434. 3- Khaled M. Musallam et al Survival and
causes of death in 2,033 patients with
non-transfusion-dependent ß-thalassemia.
Haematologica. 2021 Sep 1 106(9) 24892492. 4-
Vicki Moore Outcomes in Non transfusion-Dependent
ß-Thalassemia With Luspatercept or Placebo.
HematologyAdvisor December 14, 2021.