Quick Reference of Thallasemia

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MANAGEMENT OF TRANSFUSION DEPENDENT THALASSAEMIA QUICK REFERENCE FOR HEALTH CARE PROVIDERS

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KEY MESSAGES

• Thalassaemia is an inherited blood disorder affecting all major ethnicities in Malaysia.

• AllpatientswithMCH<27pgshouldbescreenedforthalassaemia.

• Cascadescreeningandappropriategeneticcounsellingshouldbeprovidedtotheimmediateandextendedfamilymembersofanindexpatient.

• Allthalassaemiamajorpatientsshouldreceivesafeandoptimalbloodtransfusions.

• Monitoringandtreatmentofironoverloadmustbeoptimisedtoimprovesurvival.

• Monitoring and treatment of cardiac, infective and endocrine complications willensurebetterqualityoflifeandsurvival.

• Effective patient management requires good collaboration between transfusionmedicine,laboratoryandclinicalservices.

• Bonemarrowtransplantationfromamatchedsiblingdonor isanestablishedcurativetreatmentoption.

This Quick Reference provides key messages and a summary of the main

recommendations in the Clinical Practice Guidelines (CPG) Management

of Transfusion Dependent Thalassaemia (November 2009).

Details of the evidence supporting these recommendations can be found

in the above CPG, available on the following websites:

Ministry of Health Malaysia : h t t p : / / w w w . m o h . g o v . m y

Academy of Medicine Malaysia : h t tp : / /www.acadmed.org.my

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DIAGNOSTIC CRITERIA

CliniCal Features laboratory Features

thalassaemia Major(presentationusuallyat4-6 months or child youngerthan2yearsold)

AnaemiaHepatosplenomegalyGrowthfailure/retardation

Hb :<7g/dLHbF:>90%HbA2:normalorhighHbA:usuallyabsent

thalassaemia intermedia(presentationatlaterage)

Milder anaemiaThalassaemia faciesHepatosplenomegaly

Hb :8-10g/dLHbF:>10%HbA2:4-9%,if>10%-suggestsHbEHbA:5-90%HbHdisease:presenceofHband

b thalassaemia trait Normal to mild anaemiaNo organomegaly

Hb:>10g/dLMCH:<27pgHbF:2.5-5%HbA2:4-9%,if>20%suggestsHbEtraitHbA:>90%

a thalassaemia trait Normal to mild anaemiaNo organomegaly

Hb:>10g/dLMCH:<27pgHbanalysis:normalHinclusionmaybepresentDNAstudiesmaybenecessary

• Formoredifficultcases,molecularstudiesmaybeemployed

Transfusionshouldbeinitiatedwhenthepatientisconfirmedtohavethalassaemiamajorand Hb<7g/dLmorethan2weeksapart.

In thalassaemia intermedia, consider transfusion when patient has failure to thrive or bonydeformitiesorextramedullarymasses.

Allpatientsshouldhave full redcellphenotypingconsistingofABO,Rh,Kell,Kidd,DuffyandMNSspriortofirsttransfusion.

Pre-transfusionHbshouldbekeptbetween9–10g/dL.

PosttransfusionHbshouldbebetween13.5-15.5g/dL.

Freshblood<14daysandleucodepletedbloodareadvisable.

Volumeoftransfusion:15–20ml/kg,2–4weeksapart.

Inthepresenceofhypersplenism,considersplenectomy.

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Mild Moderate severe

Serumferritin(µg/L) <2500 2500-5000 >5000

LIC(mgFe/gDW) <7 7-15 >15

CardiacT2*MRI(ms) >20 10-20 <10

ALGORITHM FOR IRON CHELATION IN TRANSFUSION DEPENDENT THALASSAEMIA

Start Iron Chelation Therapy if serum ferritin > 1,000 µg/L

(usually at age 2-3 years)

MonotherapyFirst line Iron Chelator: DFO 20-40 mg/kg/day (children) and up to 50 - 60 mg/kg/day (adults) s/c slow infusion 5 nights per week

If inadequate chelation with DFO, consider:• DFX 20 - 30 mg/kg/day in young children more than 2 years old OR • DFP 75 - 100 mg/kg/day if more than 6 years old

Mild iron overload:Serum ferritin < 2,500 µg/L T2*heart > 20 ms LIC < 7 mg Fe/g DW(If MRI is available, T2* MRI is indicated for those >10 years old)

Continue current iron chelator and aim for serum ferritin < 1,000 µg/L

Check compliance, Optimise dose of current drug or monotherapySwitch to alternatives:- Another monotherapy- Consider DFP-DFO combination- Intravenous DFO

Moderate to severe iron overload:Serum ferritin > 2,500 µg/L T2*heart < 20 ms LIC > 7 mg Fe/g DW(If MRI is available, T2* MRI is indicated for those >10 years old)

Abbreviations: DFO – Desferrioxamine DFP – Deferiprone DFX – Deferasirox LIC – Liver Iron Concentration

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no. Monitoring assessMent and investigations

1. Bloodtransfusion HBsAg,AntiHCVandAntiHIV6monthly

2. Growth Weight,heightandphysicalexamination3-6monthly

3. Ironoverload Serumferritin3monthly

Patient>10yearsoldECGandcardiacechocardiographyannuallyLICbyMRI1–2yearlyCardiacMRIT2*1–2yearly

4. Drugtoxicity

Desferrioxamine Auditory/ophthalmologyannually

DeferiproneFullbloodcountweeklyALT3monthly

DeferasiroxRenalprofileandurineproteinmonthlyALTmonthlyAuditory/ophthalmologyannually

5 Complications* Especiallyinolderpatients>10yearsold

5.1 Growthfailure

Testfordiabetesmellitus,hypothyroidism,delayedpuberty,zincdeficiency,bonedisorders,DFOtoxicityBoneageassessmentGHstimulationtests(inreferralcentre)

5.2Delayedpubertyandhypogonadism

Tanner staging 6 monthlyLH,FSH,oestradiolortestosteronePelvicultrasoundforgirlsGonadotropin releasinghormone (GnRH) stimulation testif necessary

5.3 Hypothyroidism FreeT4andTSH

5.4 Diabetesmellitus FastingplasmaglucoseorOGTT

5.5 Osteoporosis/Osteopaenia

Serumcalcium,phosphate,alkalinephosphatase25-OHVitaminDSerumzincSpinalradiograph(APandlateralviews)DEXAscan

5.6 HypoparathyroidismSerumcalcium,phosphate,alkalinephosphataseSerummagnesiumParathyroid hormone

5.7 HypoadrenalismBaselinecortisolat8.00–9.00amACTHstimulationtest

*Monitorannuallyandrefertoappropriatespecialistformanagement

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treatMent Criteria treatMent

HEPATITIS B

1. HBsAgpositivity>6monthsAND

2. Serum HBV DNA > 20,000 IU/ml (105copies/ml) inHBeAgpositivecases,serumHBVDNA>2,000IU/ml (104 copies/ml)inHBeAgnegativecases

AND

3. PersistentorintermittentelevationinALT/ASTlevels, >2Xupperlimitofnormalorsignificantliverdiseaseonliverbiopsy

Interferon a (IFN a) for 4-6 months forHBeAgpositive patients and at least a yearforHBeAgnegativepatients

orPeg-IFN for at least six months for HBeAgpositive patients and 12 months for HBeAgnegativepatients

orLamivudine

HEPATITIS C

1. Persistentanti-HCVpositivity>sixmonthsAND

2. SerumHCVRNApositivity(regardlessofviraltitre) AND

3.Significantliverdiseaseonliverbiopsy

Combination therapy (either conventional orPEG-IFN)withribavirin

TreatmentdurationdependsonHCVgenotype

BACTERIAL INFECTIONS

Significantfeverespeciallypost-splenectomy StopironchelationtherapyBroadspectrumant i-Klebsiel laand anti-Pseudomonalagents(3rd generation cephalosporin±aminoglycoside)

CARDIAC SIDEROSIS

Asymptomatic,mildtomoderatecardiacsiderosis (T2*10-20ms)andnormalcardiacfunction

Intensifyironchelationmonotherapyorswitchtocombinationtherapy

Symptomaticorseverecardiacironoverload Appropriatecardiac therapy,continuousivDFOorcombinationtherapy

DELAYED PUBERTY

Absenceofpubertalchangesat13yearsold(girls) and14yearsold(boys)

Girls:Oralethinyloestradiolorconjugated oestrogenpreparation

Boys:Depottestosterone

SHORT STATURE TreatothercausesofshortstatureGrowthhormoneinjectionmaybeconsidered ifconfirmedgrowthhormonedeficiency

DIABETES MELLITUS Subcutaneousinsulininjection

HYPOTHYROIDISM(primaryorcentral) OralL-thyroxine

OSTEOPOROSIS/OSTEOPAENIA OralcalciumandVitaminDsupplementsBisphosphonatesmaybeconsideredinosteoporosis

HYPOPARATHYROIDISM Oralcalcitriolandcalcium

HYPOADRENALISM Oralhydrocortisone

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Quick Reference of Thallasemia