1. Thalassaemiasa)B-Thalassaemia-> 1. Major 2. Intermedia 3. Minima and minor 4. Traitb) A-Thalassaemia->1. Major 2. HbH 3. TraiT 4. Silent
Introduction 1. Thalassemia comes from the Greek word "thalassemia" which means "anemia by-the-sea." 2. The most common genetic disorder worldwide 3.Children with thalassemia: a) shorter red cell life b) HbF until older age c) red cell prone to oxidative stress
Epidemiology Worldwide- 3% for B-Thalassemia SEA- 5-10% for A-Thalassemia
Thalassemia Major ( Cooley’sanemia)1.Hb- Bo/Bo2. Chromosome 113. Epidemiology:- Indian subcontinent, Mediterranean, Middle East The estimated carrier rate for beta- thalassemia inMalaysia is 3.5-4%. There were 4768 transfusion dependent thalassemia major patients as of May 2010 (Data from National Thalassemia Registry).
Pathophysiology Mutation of B- globin chain deficiency of B-globin chain Increase in gamma and delta chainIncrease in HbF and HbA2, excess A4 Precipitation of globin chain Ineffective erythropoiesis(cell death)
Clinical manifestations:1. Presenting Age: 4- 6 months of life2. Presented with : a) Weakness b) Cardiac decompensation3.Hb level : </=4g/dl4. General symptoms(b4 transfusion)1. Fatigue2. Poor appetite3. Failure to thrive
Lab Findings and investigations 1. Hb Electrophoresis/ HPLC- a) Increased HbF b)Decreased or absent HbA c) HbA2 variable 2. FBC , peripheral blood film– anemia, high reticulocytes, numerous nucleated cell, microcytosis 3. Unconjugated bilirubin- increased 4. Serum ferritin and transferrin – elevated ( even b4 transfusion) 5. Red cell phenotyping (ideal)–transfusion 6.X- ray- bone marrow hyperplasia
7. DNA analysis (optional)- confirm, prenatal diagnosis, detection of carrier 8.Liver function test 9.Infection screen- HIV, Hepatitis B and C, VDRL (before first transfusion) 10. HLA typing ( for all patient with unaffected siblings)
Treatment?When- completed blood investigation to confirm diagnosis:1. Blood transfusion ( life-long)Indication:a)Hb<7g/dl ( 2times, 2 weeks apart with no other factor eg infection)b) Hb>7g/dl if impaired growth, bones changes, hepatosplenomegaly. Goal : Hb – 9.5 g/dl( Post)Maintain : Hb 12-12.5g/dl and <15.5g/dl (mean post)Interval : 2-6 weekly interval( mean 4)Volume : 15-20mls/kg (max) over 4 hours.
2. Assess Iron Overload via : a) Liver biopsyb) Ferritometryc) Serum Ferritin3. Iron Chelation ( Prevent hemosiderosis, haemochromatosis)- Deferoxamine( Desferal) / Deferiprone
4. SplenectomyIndications: a)T. Intermediate- falling steady state Hb b) Transfused- Rising transfusion needsBlood consumption volume of PRBC >1.5x normal or >200-220ml/kg/year in those >5 years age to maintain norm level* Prophylaxis5. Bone marrow transplant(cure!)HLA- matched siblings
Iron chelation therapy?When- > 2years old and serum ferritin reaches 1000ng/ml (10-20 tranfusions)A) Deferoxamine(Desferal) given: -> SC over 10-12 hours via continuous infusion pump -> 5-7 days per week (severity dependent)Aim: Serum ferritin <1000ng/ml. Side effects: 1. Local skin irritation 2. Yersinia infection (fever, abdominal pain, diarrhea)
Toxicity >50mg/kg/day in low serum ferritin 1. Ototoxicity 2. Retinal changes 3. Bone dysplasia B) Deferiprone/L1( Kelfer/Ferriprox) Given: oral Dosage : 75-100mg/kg/day in 3 doses/daily (combination)-Less effective and side effectsa) Neutropeniab) Arthritisc) Hepatic fibrosis
MonitorEach time1. Clinical assessment : Height, Weight, Liver and Spleen size2. Pre transfusion Hb, platelet , Post transfusion(half hour)3. Volume transfusedEvery 3-6 months1 Growth &Development2.Serum Ferritin3.LFT
Every year (/more)1. Growth &Development2. Endocrine assessment( RBS,T4/TSH,Ca(PTH and vit D,Po4)3. Pubertal and Sexual (>10years)4. FSH,LH,Estrogen and testosterone5. Infection screen (Hep B and C , HIV, VDRL) (6 monthly)6. Cardiac assessment- ECG, Echo7. Liver Iron store
Thalassemia intermedia1. Combination of B- thalassaemia mutation ( Bo/B+, Bo/B variant, E/Bo)2. Late onset (> 2 years of age)2. HB level – >7g/dlControversy whether to transfuse
Thalassaemia minima or minor HB- heterozygotes (Bo/B, B+/B+) ( more severe than trait but less severe than intermediate Investigate phenotype and monitor iron accumulation
B- Thalassemia trait Misdiagnosed as iron deficiency Test: 1.Presistent red cell distribution width 2. Hb electrophoresis- Increased HBF and HBA2.
Alpha- Thalassemia Epidemiology:Malaria area especially in SEA.Intro1. 4 A-globin chain and therefore 4 deletional A Thalssaemia phenotype.2. Chromosome 16
A- Thalassaemia Deletion of A-globin Clinical manifestations geneSilent Trait 1 Diagnosed after birth with 2 gene deletion of Hb H ( B4)- Africa- AmericanA- Thalassaemia trait 2 Microcytic anemia, Hb elctrophoresis norm, ( eliminate Fe def and conf DNa testingHb H disease 3 Marked microcytosis and anemia, HB electrophoresis. ( may be assymtomatic)A- Thalassaemia Major 4( Transfusion Hydrop fetalis ( epsilon(Hb Barts Syndrome) dependent) globin gene must be present to survive, with mainly Barts’s , Gower 1, 2, Portland)
Hb B -mild to moderate anaemia, hepatosplenomegaly, and jaundice. Some affected individuals also have bone changes(overgrowth of the upper jaw and an unusually prominent forehead).Alpha Thalassaemia Major Additional signs and symptoms:severe anaemia, hepatosplenomegaly, heart defects, and abnormalities of the urinary system or genitalia. serious complications for women during pregnancy: preeclampsia) premature delivery, and abnormal bleeding.
Treatment 1. Folate supplementation 2. Splenectomy 3. Transfusion- Intermittent for severe anemia (Hb H) Chronic transfusion (survivors of Hydrop fetalis) 4. Bone marrow transplant
Reference Nelson Textbook for Paediatrics, 17th Edition Illustrated Paediatrics, 3rd edition, Lissauer Clayden. Paediatric Protocols Malaysia, 2nd Edition CPG Malaysia www.Emedicine.com