Thalassaemia
‘ Named from the Greek Word for
sea, thalassa- A group of Autosomal
Recessive Hematologic Disorders that Caus...
Inherited Hemoglobin Disorders
IN MALAYSIA….
Non Transfusion
Dependent Thalassemia
Guideline for Management of Non-transfusion Dependent Thalassaemia 2013, Thalassaemia International Foundation
(TIF)
Hb-E/β Thalassemia
O Due to G to A substitution in codon no. 26 of beta

globin gene
O Produce abnormal Hb and abnormally ...
O HbE/β thalassemia classified into:
O Severe (Hb 4-5g/dL, transfusion dependent, clinical

symptoms similar to beta thala...
Genotypes/phenotypes Thalassemia in Asia - by Suthat Fucharoen MD of the Thalassemia Research Center Institute of Molecula...
HbH Thalassemia
(α Thalassemia Intermedia)
Transfusion Therapy
Transfusion Therapy
O Optimum Transfusion Therapy:
O Permit normal growth and activity level
O Prevent skeletal changes as...
When to start regular transfusion
in NTDT
O 1st few months – careful assessment
O Practical recommendations:
O Hb level mu...
O Frequent transfusion is considered with

reassessment of tapering or withdrawal when a
sustained clinical benefits is ac...
O Transfusion may be considered in primary

prevention (high risk population), management
or secondary prevention of follo...
O Blood products:
O Storage <2weeks, conditioning to achieve mean
O
O
O
O

24-hour-post-transfusion RBC survival >75%
Leuc...
O Transfusion regimes:
O Moderate transfusion: maintain pre-Hb 9-10g/dL
O Hyper transfusion: maintain pre-Hb >10g/dL, imme...
Effectiveness of Transfusion Therapy:
O Measured in terms of rate of fall in level of Hb shouldn’t

exceed:
O 1g/dL/week i...
Problems of Thalassemia Transfusion
Programme in Developing Countries:
O Inadequate voluntary blood donation
O Absence of ...
Chelation
Therapy
O Thalassemia intermedia:
O If transfusion >8 units/year  reclassified as beta

thalassemia major
O Need to identify comp...
Standard of care guidelines for thalassemia 2012- children’s hospital and research centre
Standard of care guidelines for thalassemia 2012- children’s hospital and research centre
Oakland
DFO
(100% effectiveness as 1g of DFO excrete 93mg of
iron)

Desferrioxamine
(DFO)
Works in 2 ways

Rapid process: reduce t...
O IV desferrioxamine
O 24H infusion
O 50mg/kg/day  7 days a week
O Indications:
O Severe iron overload, persistent >2500u...
Deferiprone (L1)
(1,2 dimethyl-3-hydroxypyrid-4-one)
O 3 molecules of L1 combine with 1 atom of iron

(bidentate) & passed...
O Adverse reaction of medication
O Neutropenia
O <500-1500/mm3  neutropenia (more common)
O < 500/mm3  agranulocytosis
O...
Deferasirox (exjade)
O Dose
O 20-30mg/kg/day
O Remove iron from liver as effectively as DFO at 35-

40mg/kg/day
O Combinat...
Standard of care guidelines for thalassemia 2012- children’s hospital and research centre
Oakland
Thank you
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Thalassaemia

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  • Notes:Ferritin may be a misleading measurement; liver iron is the much more accurate one. Young children may have more toxicity with chelators and may need dose adjustment.Therapeutic index (TI) is often used in determining the deferoxamine dose when ferritin is analyzed. The therapeutic index is equal to the mean daily dose (mg/kg) / serum ferritin (mg/l). The targetis to maintain the value of TI at under 0.025. The mean daily dose of deferoxamine is calculated by multiplying the dose administered in each treatment by the total number of doses administered perweek, then dividing by seven—the number of days in a week. Ferritin measurements should be accompanied by periodic LIC measurements.Consultation with thalassemia specialists should be considered in dose adjustments.Nontransfused or intermittently transfused patients should receive chelation therapy and have their iron stores closely monitored. Their dosing should be modified on an individual basis withconsultation.LIC refers to dry weight, which is the standard method for reporting liver iron by liver biopsy and MRI. The wet weight conversion, which is a direct measurement determined by SQUID, is achievedusing a divisor of 5 to 6.
  • Thalassaemia

    1. 1. Thalassaemia ‘ Named from the Greek Word for sea, thalassa- A group of Autosomal Recessive Hematologic Disorders that Cause Hemolytic Anemia due to Decreased or Absence Synthesis of a Globin Chains and Impairs Erythropoiesis’
    2. 2. Inherited Hemoglobin Disorders
    3. 3. IN MALAYSIA….
    4. 4. Non Transfusion Dependent Thalassemia
    5. 5. Guideline for Management of Non-transfusion Dependent Thalassaemia 2013, Thalassaemia International Foundation (TIF)
    6. 6. Hb-E/β Thalassemia O Due to G to A substitution in codon no. 26 of beta globin gene O Produce abnormal Hb and abnormally sliced nonfunctional mRNA O HbE : produced at reduced rate  behaves as mild β+ thalassemia
    7. 7. O HbE/β thalassemia classified into: O Severe (Hb 4-5g/dL, transfusion dependent, clinical symptoms similar to beta thalassemia major) O Moderate (Hb 6-7g/dL, transfusion independent, clinical symptoms as beta thalassemia intermedia) O Mild ( Hb 9-12g/dL, transfusion independent, asymptomatic)
    8. 8. Genotypes/phenotypes Thalassemia in Asia - by Suthat Fucharoen MD of the Thalassemia Research Center Institute of Molecular Biosciences, Mahidol University, Thailand http://www.slideshare.net/Thalassaemia_Intl_Fed/overview-of-genotypes-and-phenotypes-of-thalassemia-in-asia?from_search=44
    9. 9. HbH Thalassemia (α Thalassemia Intermedia)
    10. 10. Transfusion Therapy
    11. 11. Transfusion Therapy O Optimum Transfusion Therapy: O Permit normal growth and activity level O Prevent skeletal changes associated with marrow hyperplasia O To reduce splenomegaly/hypersplenism O To decrease absorption of dietary iron O Leads to minimal iron overload
    12. 12. When to start regular transfusion in NTDT O 1st few months – careful assessment O Practical recommendations: O Hb level must not be an indicator- unless in severe anemia (Hb <5g/dL) O Occasional blood transfusion in anticipated acute stress, hemoglobin drop or blood loss O Pregnancy O Surgery O infections
    13. 13. O Frequent transfusion is considered with reassessment of tapering or withdrawal when a sustained clinical benefits is achieved: O Declining Hb level in parallel with profound O O O O O O O enlargement of spleen (rate 3cm/year in period of maximal growhth and development) Growth failure Poor school performance Reduce exercise tolerance Failure of secondary sexual development in parallel with bone age Signs of bony changes Frequent hemolytic crisis (HbH disease) Poor quality of life
    14. 14. O Transfusion may be considered in primary prevention (high risk population), management or secondary prevention of following complications O Thrombotic or cerebrovascular disease O Pulmonary hypertension with or without secondary heart failure O Extramedullary hematopoietic pseudotumor O Leg ulcers
    15. 15. O Blood products: O Storage <2weeks, conditioning to achieve mean O O O O 24-hour-post-transfusion RBC survival >75% Leucodepleted packed cells with hemoglobin content more than 40g ABO and Rh(D) matched blood Rh (C,c,E,e) and Kell matching highly recommended Viral screeening
    16. 16. O Transfusion regimes: O Moderate transfusion: maintain pre-Hb 9-10g/dL O Hyper transfusion: maintain pre-Hb >10g/dL, immediate post transfusion Hb 14g/dL, return to baseline by 3-4weeks O Super transfusion: maintain pre-Hb>11g/dL or hematocrit >35% O Post-transfusion Hb should not exceed 16g/dL due to high risk of hyperviscosity O Amount: O 10-20ml/kg/day  rate 5-7ml/kg/H (~3-4weekly) O Cardiac insufficiency  1-3ml/kg/H (not exceed 5ml/kg/H) (~2weekly) O Annual 180-200ml/kg
    17. 17. Effectiveness of Transfusion Therapy: O Measured in terms of rate of fall in level of Hb shouldn’t exceed: O 1g/dL/week in splenectomized patients O 1.5g/dL/week in non-splenectomized patients O Investigations: O Antibodies (alloimmunization) to RBCs O Enlarged spleen (hypersplenism) and/or hepatomegaly O Poor quality of blood – shorter life span, function less effectively O Bleeding from GIT O Increased rate of destruction due to use of medications (e.g. ribavirin) O Increased rate of destruction due to infections
    18. 18. Problems of Thalassemia Transfusion Programme in Developing Countries: O Inadequate voluntary blood donation O Absence of component preparation facilities of O O O O blood centres, hence packed RBC may not be available Absence of extended phenotyping testing in patient and donor No screening facilities for irregular antibodies Leucofilters are generally unaffordable by many Poor chelation compliance and affordability
    19. 19. Chelation Therapy
    20. 20. O Thalassemia intermedia: O If transfusion >8 units/year  reclassified as beta thalassemia major O Need to identify complications of TI  age related complications associated with chronic anemia O Serum ferritin >500mcg/dL in untransfused patient O Ferritin measurement alone is insufficient O Need annual assessment of liver iron concentration or MRI T2* in late childhood or early adolescnce
    21. 21. Standard of care guidelines for thalassemia 2012- children’s hospital and research centre
    22. 22. Standard of care guidelines for thalassemia 2012- children’s hospital and research centre Oakland
    23. 23. DFO (100% effectiveness as 1g of DFO excrete 93mg of iron) Desferrioxamine (DFO) Works in 2 ways Rapid process: reduce toxicity of iron in body by mopping up free radicals Slow process: binds with iron to form ferrioxamine 2 main sources of iron pools 1st pool: iron formed by breakdown of RBC (70%) 2nd pool: liver (largest iron storage) released when ferritin and hemosiderin broken down in liver Excreted in urine Excreted in stools Convert Fe3+ to Fe2+ (easily moved and bound to DFO Vitamin C Should be given at the same time/ 30 min after chelation starts 50mg/day in <10 yrs old, 100mg/day in older children If not on chelation: may promote increased circulating Fe2+
    24. 24. O IV desferrioxamine O 24H infusion O 50mg/kg/day  7 days a week O Indications: O Severe iron overload, persistent >2500ug/L O LIC >15ug/g/dry weight liver O Heart complications O Female with severe iron overload planning for pregnancy O Patient planned for bone marrow transplant/ chronic active hepatitis C O Others: over 8-12H infusion, more than 5 days/week O Dose 40-50mg/kg/day
    25. 25. Deferiprone (L1) (1,2 dimethyl-3-hydroxypyrid-4-one) O 3 molecules of L1 combine with 1 atom of iron (bidentate) & passed in the urine O Pools: same as DFO + small molecular size enables them to enter cells and remove intracellular iron O Dosage: 75-100mg/kg/day in 3 divided dose
    26. 26. O Adverse reaction of medication O Neutropenia O <500-1500/mm3  neutropenia (more common) O < 500/mm3  agranulocytosis O Look for signs of sepsis/infection. May need to stop L1 immediately O Resumes back if TWC >3000/mm3, ANC >1000/mm3, platelet >100000/mm3 O Joint pain/swelling- may be due to transferred of iron from other pools to the joint O GIT- nausea or vomiting (mild) O Zinc deficiency  L1 may bind to other metals e.g. zinc O Liver toxicity
    27. 27. Deferasirox (exjade) O Dose O 20-30mg/kg/day O Remove iron from liver as effectively as DFO at 35- 40mg/kg/day O Combination therapy – contraindicated O Provide 24H protection O Tridentate chelator  bind to Fe3+ & excreted via stool O Has the ability to remove iron from heart O Adverse effects: O GIT: diarrhea/nausea/vomiting O Renal or liver impairment –rare
    28. 28. Standard of care guidelines for thalassemia 2012- children’s hospital and research centre Oakland
    29. 29. Thank you
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