This document provides an overview of non-transfusion dependent thalassemia (NTDT), which includes conditions like beta thalassemia intermedia and hemoglobin E/beta thalassemia. NTDT is characterized by ineffective erythropoiesis, chronic anemia, and iron overload without requiring lifelong transfusions. Patients with NTDT present after age 2 with anemia symptoms and are at risk for complications involving bones, liver, heart, and endocrine and blood clotting issues. Management includes monitoring iron levels and using chelation therapy if needed, screening for complications, and occasionally transfusions or hydroxyurea.

1. Non-transfusion-
dependent Thalassemia
Abdullah Aldhban
Pediatric Resident R4

2. OBJECTIVE
Thalassemia Overview
1
TDT /NTDT
2
Pathophysiology and clinical picture
3
Complication of NTDT
4
Management And Prevention
5

6. Thalassemia Overview

7. what is the thalassemia?
Homozygous or heterozygous defect Of globin molecule lead to impalance in
production Globin chains.
• Two major types of thalassemia:
– Alpha (α) - Caused by defect in rate of synthesis of
alpha chains.
– Beta (β) - Caused by defect in rate of synthesis in
beta chains.

8. mode of inheritance ?
Autosomal Recessive

9. Beta thalassemia
Beta thalassemia caused
by genes mutation on
chromosome 11

10. Alpha thalassemia
Alpha thalassemia caused by gene
mutation on chromosome 16

12. Non-transfusion dependent Thalassemia /Transfusion dependent
Thalassemia
12

13. Classification Of Thalassemia on dependence of Transfusion
Transfusion dependent Thalassemia
• β Thalassaemia major
• severe Hb E/β Thalassaemia
Non-transfusion dependent
Thalassemia
• Beta Thalassaemia intermedia
• Alpha Thalassaemia
intermedia(Hemoglobin H disease)
• Hemoglobin E disease
• Mild /moderate hemoglobin E-beta
Thalassaemia

14. How To differentiate BW TDT And
NTDT

15. What is the NTDT And what is it Include ?
Non-transfusion-dependent Thalassemia
Group of thalassemic phenotypes that not require lifelong regular blood transfusions for survival
may still need transfusions for specific clinical indications such as infection, growth failure, pregnancy, and surgery
The three most studied NTDT Group are
 beta-thalassemia intermediate
 alpha-thalassemia (HbH disease)
 hemoglobin E/beta-thalassemia

16. Thalassaemia intermedia (TI)
 Thalassaemia intermedia (TI) lie between thalassaemia minor (heterozygous state) and
major (homozygous state)
 Differentiation at presentation between thalassaemia major and thalassaemia intermedia
is essential for designing appropriate treatment .

17. Differentiation at presentation between thalassaemia major and
thalassemia intermedia ?

18. alpha-thalassemia (HbH disease)
 loss of 3 alpha-globin genes(-α/--) leads to a condition known as HbH disease,
or alpha thalassemia intermedia.

19. β-thalassemia/HbE
Haemoglobin E results from a G→A on code number 26 on b glubuline
Hb E/β-thalassaemia results from co-inheritance of a β-thalassaemia allele
from one parent and the structural variant Haemoglobin E from the other.

20. -
20
Clinical pictures of
NTDT

21. Clinical pictures
-Patient with NTDT often present older than 2 years old with symptoms
of anemia, such as pallor, fatigue, dizziness, tachycardia, and dyspnoea
-NTDT patients are at risk of developing complications Like gallstones
hepatosplenomegaly , skeletal deformities, growth retardation.

22. Pathophysiology of NTDT
22

23. Three main factors are responsible for the clinical sequelae of NTDT Is
1- ineffective erythropoiesis
2- chronic anaemia
3 - iron overload
23

24. Ineffective erythropoiesis
Failure in maturation of erythroid progenitor precursors
decrease erythrocytosis from Bone marrow
Lead to bone marrow expansion and development of extramedullary hematopoiesis in
the chest, abdomen, and pelvis, causing skeletal deformities, and hepatosplenomegaly

25. Iron overload In NTDT
Decrease In hepcidin synthesis ( as the sequele of Ineffective erythropoiesis)
Increasing in intestinal iron absorption
Iron overload
liver cirrhosis, liver fibrosis, Endocrinopathies, pulmonary hypertension, cerebrovascular
disease

26. Iron overload In NTDT
All patients with NTDT ≥10 years of age should be frequently assessed Iron
overload
Assessment by using serum ferritin level every 3 months
Iron chelation therapy should be started Serum ferritin level >300 ng/ml
Deferasirox therapy should be administered as follows:
> Starting dose: 10 mg/kg/day
> Dose escalation after 1 month as follows:
- serum ferritin ≥300 to ≤1500 ng/ml: no escalation
- serum ferritin : 1500 to ≤3000 ng/ml: escalate to 15 mg/kg/day

27. Complication of NTDT
27

28. cardiopulmonary complications
Multiple cardiopulmonary complications, including congestive heart failure, pericardial changes, valvular
defects, and, most importantly, pulmonary hypertension
Annual routine echocardiography to assess tricuspid-valve regurgitant jet velocity rejection (TRV) is
recommended
Patients with possible or confirmed pulmonary hypertension may benefit from the
following interventions
# Blood transfusion
# Hydroxyurea
# Sildenafil citrate
# Adequate control of iron overload status
# Anticoagulant therapy

29. Hepatobiliary complications
-The majority of iron overload deposits are in the liver that will incrase risk of liver
fibrosis, cirrhosis
-Patients with NTDT ≥10 years should be screened for hepatic function and disease as
follows:
1-Liver function tests: every 3 months for all patients
2- Liver ultrasound: annually in patients with serum ferritin level ≥800 ng/ml
3- Alpha-feto protein: annually in cirrhotic patient

30. in Patients with NTDT who are ≥10 years
-Evaluation for growth every 6 months if fall more than 5% , decreased height velocity or delayed bone
age we have to refer him to Endocrinologist
- Annual screening with Free thyroxine and thyroid-stimulating hormone , Parathyroid hormone ,
Adrenocorticotropic hormone stimulation test
Endocrinopathies
Iron overload causes dysregulation of the hypothalamic-pituitary axis
lead to endocrine disorders including delayed puberty, growth retardation, hypogonadism, diabetes mellitus,
hypothyroidism, hypoparathyroidism, and adrenal insufficiency

31. -Annual screening for bone mineral density should be started from age 10 years by Vitamin D and calcium
Bone disease
subsequent of bone marrow expansion from ineffective erythropoiesis
Lead to Bone deformities, including frontal bossing, maxillary hypertrophy, depression of nasal bridge, shortening
of long bones and osteopetrosis

32. Thrombotic disease
especially
> Patients with a diagnosis of β-thalassaemia intermedia
> Splenectomized patients
Patients with a history of pulmonary hypertension
Patients with iron overload level ≥800 ng/ml)
> Patients with a personal or family history of thrombosis
Prophylactic intervention with anticoagulants or antiaggregants in high-risk patients should follow local or international guidelines.
Duo to chronic hypercoagulable state , endothelial injury from iron overload
high risk of thrombosis

33. Blood transfusion
Indication of
Acute Transfusion
-Hemoglobin level < 5 gm/dL , Surgery , Infections
Chronic Transfusion
 Declining hemoglobin level with profound enlargement of the spleen
 Growth failure (height is more indicative of growth pattern than weight)
 Poor performance at school
 Diminished exercise tolerance
 Failure of secondary sexual development along with bone age
 Signs of bony changes
 Frequent hemolytic crisis (hemoglobin H disease)
 Poor quality of life

34. Indication of Splenectomy In NTDT
Splenectomy should be Consider after age of 5 y in cases of:
 Symptomatic Hypersplenism with worsening anaemia, leucopenia, or thrombocytopenia
 Massive splenomegaly (largest dimension >20 cm) with concern about possible splenic rupture
Whenever splenectomy is indicated, patients should receive the following vaccines At least 2 weeks
before procedure
1- Pneumococcal 23-valent polysaccharide vaccine
2-Haemophilus influenzae vaccine
3- Meningococcal polysaccharide vaccine
4- Influenza vaccine, annually

35. Indication of Hydroxyurea In NTDT
There are no randomized clinical trials to recommend an evidence-based use of hydroxyurea in NDTD
patient But there is some Cohort study's recommend to start Hydroxyurea In :
 -Thalassemia intermedia homozygous for the XmnI polymorphism
 Patients with the following clinical morbidities:
# Leg ulcers
# Pulmonary hypertension
# Extramedullary hematopoietic pseudotumors
Hydroxyurea dose starting from 10 mg/kg/day with dose escalation by 3-5 mg/kg/day every 8 weeks to
the maximal not 20 mg/kg/day.

36. REFERENCES
 Non-Transfusion-DependentThalassemia: A Panoramic Review.Medicina 2022, 58, 1496.
https://doi.org/10.3390/medicina58101496Academic Editors: Roberto Castelliand Paul Imbach
 Ali Taher, Elliott Vichinsky, Khaled Musallam, Maria Domenica Cappellini, Vip Viprakasit, David Weatherall .
Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT). Nicosia (Cyprus):
Thalassaemia International Federation; 2017.

37. Thank you