Management of transfusion dependant thalassemia.

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Transfusion dependant thalassemias:

• 80-85% of homozygous β° thalassemias
• 25% of homozygous β⁺ thalassemias

Treatment:

1. Guidelines for Transfusion therapy:

• RBC depleted of leukocytes
• Matched for D,C,c,E,e & kell Ag
• Cytomegalovirus safe units for stem cell transplantation candidates
• Usual intervals 3-4wks
• Hb goal 9.5-10.5g/dl
• Monitor for
• Transfusion ass infections
• Transfusion ass reactions
• Alloimmunization

2. Monitoring for iron overload:

Serum ferritin: screening technique

R2 MRI Quantitative liver Iron: best indicator usually started at 10yr.

Chelation therapy:

Chelation used in case of iron overload

General after 1 yr of transfusion

S. Ferritin > 1000ng/ml

Liver Iron >5000μg/g dry weight

Not <2yrs of age

Goals

1. Prevent hemosiderosis induced tissue injury
2. Avoid chelation toxicity.

Chelators

Deferoxamine	Deferasirox	Deferiprone
I.V / S.C	Oral	Oral 2nd line
8hr/d for 5-7days/wk	O.D	T.D.S
25mg/kg - 60mg/kg	20mg/kg/d - 40mg/kg/d	75mg/kg/d - 99mg/kg/d
Excellent safety and efficacy	Adherence	Easily enter cardiac & other tissues
Skin reaction Ototoxic Retinal changes Bone dysplasia Truncal shortening	Kidney damage G.I symptoms Hepatic transaminitis	Transient Agranulocytosis C.I when febrile

3. Hydroxyurea:

Used in β thalassemia intermedia

Dose: 10mg/kg - 20mg/kg

Mean increase in Hb is 1gm/dl

Reduced risk of

• Leg ulcers
• Pulmonary HTN
• Extramedullary hematopoiesis

Risk of developing cytopenia

4. Hemopoietic stem cell transplantation:

In low risk HLA matched siblings

- survival rate is 90%

- event free survival is 80%

Gene therapy with lentiviral vectors for no donar pts 

5. Splenectomy:

Indications:

• hypesplenism
• falling steady state Hb
• ↑ transfusions frequency

Adverse effects:

• Infections risk
• Venous thrombosis
• Pulmonary HTN
• Leg ulcers
• Silent cerebral infarction

Prophylaxis:

• Prophylactic penicillin
• Immunization against capsulated bacteria

Preventive monitoring of Thalassemia pts:

1. Cardiac disease:

Major cause of death

Periodic electrocardiogram from 10yrs of age - risk of arrhythmias

Serial electrocardiogram to monitor

• Cardiac function
• Pulmonary artery pressure (Pulmonary HTN frequently occurs in non transfusion dependant pts - indication of BT)

After 8yrs chronic transfusions - cardiac hemosiderosis may occur

• Require T2 MRI for diagnosis
• Intense combination chelation therapy

2. Endocrine disease:

↓ endocrinal functions usually after 5yrs age/ 3yrs transfusion therapy due to

• Hemosiderosis in pituitary and other glands causes
• Hypothyroidism
• G.H deficiency
• Hypo parathyroidism
• Diabetes mellitus
• Osteoporosis
• Adrenal insufficiency
• Nutritional deficiencies

Measures:

Bi-annual: Height, weight, pubertal development

From 10yrs age: Bone scan

Vit D, Vit C, Zn supplementation

3. Psychological support:

• Culturally sensitive anticipatory counseling
• Early use of child life services
• Early social service consultation for financial & social issues