Kathryn Maguire - Haematology Association of Ireland

Iron Cycle

Consequences of Ironoverload• Serious clinical sequelae &,unless iron levels effectivelycontrolled, patients are likely tosuffer significant morbidity &mortality;• Tissue damage & fibrosis inliver• Heart failure• Hypothalamic & pituitarydamage• Other endocrine problemsincluding glucoseintolerance, diabetes mellitus,hypothyroidism &hypoparathyroidism

Assessment of Iron Overload• Ferritin level• Normal range (15-300ug/L)• Gives a rough estimate of the extent of iron overload• Inaccurate < 1yr• Acute phase reactant• Hepatic iron concentration is the most reliablemeasure of iron burden• the “gold standard” is a liver tissue biopsy which notonly estimates quantity of iron but allows a histologicalassessment of the distribution of haemosiderin & extentof tissue damage

Liver Biopsy showing IronAccumulation

Estimation Of Iron Overloadcont…• Non-invasive & validated methods of measuringliver iron include:• Magnetic susceptometry using superconductingquantum interference device (SQUID)• Magnetic resonance imaging (MRI T2*)• MRI more readily accessible & can also image theheart, pancreas & pituitary gland• An assessment of liver iron concentration isrecommended every 12-18 months

Paediatric patients (RBHSC) ontreatment for Iron Overload• 6 patients on a chronic blood transfusion programme:5 with Diamond Blackfan anaemia & 1 withCongenital dyserythropoietic anaemia• Current age range: 2 - 23 years• 5 of the patients initiated chelation therapy withDesferral (at 18mths - 4 yrs) & were all switched toExjade (starting at 20mg/kg/day) when it becameavailable early 2007• 1 patient started on Exjade as it was available whenchelation therapy was indicated• 1 patient placed back on Desferral (continuous IVinfusion) for a period but now back on Exjade

PatientP1R.BP2J.MP3B.CP4C.SP5J.FP6T.SDesferal started 29 mths 5 yrs 3 yrs 2 yrs 3 yrsInitial Ferritin 1500 (May ‘88) 2600 (Sept’98) 1000 1543 (June 04) 817 (Sept’04)Length on desferral 19 yrs 9 yrs 5 yrs 2 yrs 4 1/2 yrsHighest ferritin level 1955 (Feb’01) 3616 (July 05) 2851 (Dec 04) 2181 (June 05) 3522 (Jan’05)Complications Ovarian failure panhypopituitarismPortacathfractured &lodged inpulmonaryarteryMultiple gallstonesHearing deficient -hearing aidsAge Exjade started& dose18 mths125mg21 yrs750mg14 yrs500mg8 yrs375mg4 yrs375mg7 yrs250mgInitial ferritin 1698 1415 2877 1833 3/07 1488 6/06 1651Current ferritin &dose of Exjade2834250mg(24mg/kg)545650mg(16mg/kg)899 (had been4207)750mg(21mg/kg)1049Ferritin (hadbeen 3200)750mg(30mg/kg)845DesferralInfusion 4/09 -12/09Exjade750mg/500mgalt days(24mg/kg)2950 (had been 3500)500mg (28mg/kg)ComplicationsPoorappetitenone As above none Liver BX(1/09):heavy Fedeposition &early fibrosis.Loading inheart. Re-startedIV Desferral4/09. ImprovedFuture PlanFor MRI&/or liverBx 5 yrsNo siblingdonorCompatibleHLA siblingNo BMT atpresentNo siblingdonor. Not forunrelated donorBMTLiver Bx(4/09) -no loadingAnnual MRI -recent noloadingNo compatibleHLA siblingSiblingallogenic BMTFeb’10MRI & Liver BxSibling not HLAmatch. ? UnrelatedBMT

Summary• Iron released from breakdown of RBCs• With repeated blood transfusions & no specificmechanism for excretion, iron accumulates in tissues• Extensive iron -induced injury develops in heart, liver,pancreas, thyroid, & other organs• Although ferritin provides estimate of iron loading,MRI T2* & liver biopsy more reliable• Chelators: parental/oral. Oral has advantages of easeof administration, improved quality of life• Regular monitoring of bloods as well as ear & eyetests required whilst on chelation therapy