medicine.E. thalassemia.(dr.anwar shexa)
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medicine.E. thalassemia.(dr.anwar shexa) medicine.E. thalassemia.(dr.anwar shexa) Presentation Transcript

  • ‫‪THALASSEMIAS‬‬ ‫ﺍﻠﻣﺗﻮﺴﻃ ﺑﺣﺮﺍﻷﺒﻴﺾ ﻓﻗﺮ ﺪﻢ‬ ‫ﻛﻪﻢ‬ ‫ﺨﻮﻴﻧﻰ‬ ‫ﺪﻩﺮﻴﺎﻯ‬ ‫ﺴﭙﻰ‬ ‫ﻧﺎﻮﻩﺮﺍﺳﺖ‬
  • Professor Anwar Sheikha MD, FRCP, FRCPath., FCAP, FRCPA, FRCPI, FACPSenior Consultant Clinical & Lab. Hematologist Clinical Professor of HematologyUniversity of Mississippi Medical Center, Jackson, Mississippi Professor of Hematology, University of Salahaddin, Erbil, Kurdistan, IRAQ
  • IT IS VERY COMMON IN KURDISTANIT IS A VERY EXPENISIVE DISEASE IT IS PREVENTABLEIT HAS BECOME AN ADULT PROPBLEM AS WELL RESEARCH POTENTIAL
  • THALASSEMIAS AMONG THE COMMONEST GENETIC DISORDERS WORLDWIDE 5% ~ 2% α and β heterozygotes Globin Variants WORLDWIDE BIRTHRATE OF HOMOZYGOUS OR DOUBLE HETEROZYGOUS GLOBIN DISORDERS 2.4/ 1000 BIRTH2/1000 0.44/1000HbSS THALASSEMIAS SULY OR HAWLER SHOULD HAVE 440 PATIENTS/ MILLION
  • THALASSEMIAS AMONG THE COMMONEST GENETIC DISORDERS WORLDWIDE 5% ~ 2% α and β heterozygotes Globin mia VariantsTh alasse Minor % WORLDWIDE BIRTHRATE OF 7% HOMOZYGOUS OR DOUBLE r Hawle 6% HETEROZYGOUS GLOBIN DISORDERS Mos ul 4% 2.4/ 1000 BIRTH Sul y 4.6% Basra d 3.2% da Bagh .7% 0.44/1000 k 3 Duho THALASSEMIAS SULY OR HAWLER SHOULD HAVE 440 PATIENTS/ MILLION
  • BLOOD LOSS ANEMIAMARROW HEMOLYSISCAUSES
  • MAIN CAUSES OF ANEMIAIRON DEFICIENCY 29% ACD 28% ACUTE BLEEDING 18% HEMOLYSIS 18% OTHERS
  • BLOOD LOSS ANEMIAMARROWCAUSES HEMOLYSIS Hb
  • Hemoglobin
  • Hemoglobin Synthesis in the Red cell
  • Globin Chainsα 141 amino acidsβ 146 amino acidsγ 146 amino acidsδ 146 amino acidsHbA HbF HbA2αβ 2 2 αγ2 2 αδ2 2
  • Globin Chainsα 141 amino acids ‫ﮐﻮﻴﺨﺎ‬β 146 amino acids ‫ﮋﻦ‬γ 146 amino acids ‫ﮋﻦ‬δ 146 amino acids ‫ﮋﻦ‬HbA HbF HbA2αβ 2 2 αγ2 2 αδ 2 2
  • GlobinChainsSynthesis
  • Definition The thalassemia syndromes are a group of hereditary disorders in which a defect in the synthesis of one or more of the globin chains of Hb is present. Hypochromic Red cells ↓Hb Microcytic Red cells
  • Definition The continued normal synthesis of the unaffected globin chain leads to the accumulation of unstable aggregates of these unmatched globin chains. Marrow Destruction Precipitated OXIDATIVE unstable MEMEBRANE aggregates DAMAGE Splenic Destruction
  • β-Thalassemia
  • β- β-thalassemia thalassemia minor major Problem for the Problem for the Community Patient
  • Incidence of Heterozygous β ThalassemiaSouthern Italian,Sicilian, and 10%Greek populationsIn certain Greek islands & some villages of Sardinia 20% to 30%.In Southeast Asian populations 5%In African andAmerican blacks 1.5%.
  • Marriage CounselingHeterozygous Heterozygous β βThalassemia Thalassemia Male Female AT AT AA AT AT TT
  • β Thalassemia α- chains β γ Chains EXCESS Chain Precipitates α 2 γ2HbF↑↑
  • β Thalassemia α- chains β EXCESS Chain Precipitates Marrow Splenic Destruction Destruction Ineffective HEMOLYSIS Erythrpoiesis Hypersplenism ANEMIA
  • An α- Hb-stabilizing proteinblocks reactive oxygen production & reduces oxidative RBC damage
  • γ α- chains β- Chains β Thal. EXCESSα 2 γ2 Chain Precipitates MarrowHbF↑↑ Splenic Destruction Destruction HEMOLYSIS↑ O2 Ineffective Erythrpoiesis Affinity Hypersplenism↑ EPO Skeletal Changes ANEMIA Hyper metabolism HyperuricemiaProliferation ofIneffectiveErythroid Marrow
  • β Thalassemia α- chains β EXCESS Chain Precipitates Splenic Marrow Destruction Destruction HEMOLYSIS Ineffective Erythrpoiesis Hypersplenism BLOOD ANEMIA TRANSFUSION CARDIAC DEATH IRON OVER- LOAD
  • γ α- chains β- Chains β Thal. EXCESSα 2 γ2 Chain Precipitates MarrowHbF↑↑ Splenic Destruction Destruction HEMOLYSIS↑ O2 Ineffective Erythrpoiesis Affinity Hypersplenism BLOOD↑ EPO Skeletal Changes ANEMIA TRANSFUSION Hyper metabolism Hyperuricemia CARDIA C DEATH IRONProliferation of Hepcidin Down Regulation OVER-Ineffective ↑ IRON Absorption LOADErythroid Marrow
  • β β- Liver Thal. Cirrhosis SkinDusky Coloration Pancreatic β cells Diabetes Endocrine Growth Failure Hypothalamic Pituitary Adrenal Axis Secondary Sex Features BLOOD TRANSFUSION CARDIA IRON C OVER- DEATH ↑ IRON Absorption LOAD
  • Blood Picture in Homozygous Thalassemia Severe hypochromic & microcytic anemia Marked anisocytosis, poikilocytosis,misshapen microcytes, occasional macrocytes, target cells, and erythroblasts.Before and after splenectomy, ragged inclusion bodies in the cytoplasm of nucleated red cells andreticulocytes consisting of precipitated α -chains are evident after incubation with methyl violet. In well transfused patients, the blood picture may appear virtually normal, reflecting almost total suppression of endogenous erythropoiesis
  • Hemoglobin Electrophoresis ‫ﺃﻓﺴﺎ‬ <
  • α-Thalassemias
  • Father Mother αα αα αα/αα αα/αααα/αα αα/αα
  • αα/αα-α/αα --/-- --/αα --/-α
  • αα/αα-α/αα --/-- --/αα --/-αHbH Hb Barts(β4) (γ 4)
  • αα/αα-α/αα --/-- Silent Hydrops --/αα --/-α α- thal minor HbH
  • Thalassemia Intermedia 12 gm/dL Thal.Hb minor 9 gm/dL Thal. intermedia 6 gm/dL Thal. major
  • MANAGEMENT OF THALASSEMIAS VERY COSTLY ESPECIALLY IN EMERGING COUNTRIESUNDISCOUNTED LIFETIME COST OF ONE PATIENT IN UK IS > ₤800,000
  • DO NOT ALLOW ANOTHER THALASSEMIA CHILD TO BE BORN IN KURDISTANThis is the cheapest way to manage this disease
  • γ α- chains β- Chains β Thal. EXCESSα 2 γ2 Chain Precipitates MarrowHbF↑↑ Splenic Destruction Destruction HEMOLYSIS↑ O2 Ineffective Erythrpoiesis Affinity Hypersplenism BLOOD↑ EPO Skeletal Changes ANEMIA TRANSFUSION Hyper metabolism Hyperuricemia CARDIA C DEATH IRONProliferation of OVER-Ineffective ↑ IRON Absorption LOADErythroid Marrow
  • β β- Liver Thal. Cirrhosis SkinDusky Coloration Pancreatic β cells Diabetes Endocrine Growth Failure Hypothalamic Pituitary Adrenal Axis Secondary Sex Features BLOOD TRANSFUSION CARDIA IRON C OVER- DEATH ↑ IRON Absorption LOAD
  • MANAGEMENT OF THALASSEMIAS EVALUATION BLOOD GENE TRANSFUSION THERAPY IRON BMT CHELATION SPLENECTOMYHEPCIDIN NORMALLYCONTROLS IRONABSORPTION; IT IS ? HEPCIDINDOWNREGULATED ? α - STABILIZING AGENTSIN THALASSEMIA
  • Initial Evaluation of the Patient with Thalassemia Clinical assessment Hematologic evaluation (CBC, Hb electrophoresis) α:non-α globin chain synthesis ratio Red cell phenotype Serum iron, total iron-binding capacity Serum Ferritin concentration Red blood cells and serum folate Total and direct Bilirubin Serum ALT, albumin, PT, APTT Hepatitis screen Initiation of hepatitis B vaccine series Parental counseling and education
  • Monthly Evaluation of the Patient with Thalassemia History and physical examination CBC Parental counseling If receiving iron chelation therapy, compliance review
  • 6 Evaluation of the Patient with Thalassemiamonthly Serum ALT Ferritin
  • Yearly Evaluation of the Patient with Thalassemia <10 LIVER BIOPSY (Histology & HIC) Hepatitis screen Serum ALT, Albumin, PT ENDOCRINE Serum Ca2 , PO4, Mg2, Zn2 , PTH, TSH Monitoring of deferoxamine toxicity
  • >10 Evaluation of the Patient with ThalassemiaYears BIOPSY (Histology & HIC) LIVER Hepatitis screen Serum ALT, Albumin, PT Endocrinology consultation Fasting blood glucose ENDOCRINE Serum Ca2, PO4, Mg2, Zn2 Serum PTH, TSH GnRH stimulation test HEART Cardiology consultation Monitoring of Radionuclide angiography deferoxamine ?48-h Holter monitoring toxicity
  • Blood Transfusion Presence When & How? Deterioration & severity + in appetite or + of S&S of activity level, + anemia Failure of Presence growth of disfiguring & skeletal development changes Assess patient for few months after Dx before making this decision Many patients with thal. intermedia embark on a life of unnecessary B.T. if they present with an unusually low Hb during an intercurrent illness
  • TRANSFUSION REGIMENSDO NOT AVOID B.T. BECAUSE OF IRON OVERLOAD IRON ABSORPTION IS ALREADY INCREASED GOALSCorrect Anemia Suppress Erythropoiesis Inhibit increased GIT absorption of iron HYPERTRANSFUSION SUPERTRANSFUSION Pre B.T. Level Pre B.T. Level > 10 gm/dL > 12 gm/dL
  • HYPERTRANSFUSION SUPERTRANSFUSION Pre B.T. Level Pre B.T. Level > 10 gm/dL > 12 gm/dL IRON OVER LOAD Moderate Transfusion Maintain Pre-Transfusion Hb at ~ 9.5 gm/dL This regimen reduces transfusion requirements,adequately suppresses marrow activity & is associated with a lower incidence of endocrine and cardiac complications
  • Ideally Transfuse 15 mLPacked Red Cells/Kg B.Wt. every 28 to 35 days AVAILABILITY OF VOLUNTARY BLOOD DONORS
  • FFECTIVENESS OF DIFFERENT TRANSFUSION PROGRA Steady-State Hb exceeding 9 g/dL NO NO evidence Reduces direct that evidence super- the of transfusion incidence improved is of impact of associated bone super- with linear Malformations growth transfusion & superior causes on to that of regression bone other of bone metabolism regimens changes splenectomy has decreased after hypertransfusion programs
  • Type of Red Cell Concentrates Leukocyte-reduced RBC preparationsThe most convenient and cost-effective procedure depends on the financial resources PRACTICAL FILTERS EXPENSIVE Effective in reducing WBC & Frequency of FTR NEOCYTES
  • Complications of Blood Transfusion ALLOIMMUNIZATION↑ ~ LATE TRANSFUSION (> 1 to 2 years) ↑~ Highest # of B.T < Mediterranean Patients Asian 3% and 10% ~ 21% Anti-Rh Anti- Kell LOWER RATES in ABO, Rh, and Kell Ag-matched BT from 1st transfusion AIHA is more common in splenectomized patients
  • DISEASESTRANSMITTED THROUGH BLOOD TRANSFUSION HEPATITIS B HIV HEPATITIS C CMV Yersinia Malaria etc. Syphilis
  • SPLENECTOMY PAST PRESENT ~ 10 YEARS OF AGE With improved~ Annual Transfusion transfusion, Requirement hypersplenism > is reduced & many patients 200 to 250 ml do not require Packed cells/ splenectomy kg B. Wt. PARTIAL SPLENECTOMY
  • SPLENECTOMY OPSIStreptococcus Neisseria pneumoniae meningitides Hib DELAY SPLENECTOMY UNTIL AFTER AGE 5 Daily Oral PartialPneumovax Penicillin Splenectomy
  • IronChelationDOUBLES LIFE EXPECTANCY
  • Iron Chelation DeferoxamineDesferrioxamine Desferal
  • Thalassemia Survival without (Group 1) & with (Group 2) Effective Chelation
  • Survival Beyond 12 Years EFFECTIVENESS OF DFO
  • EXPENSIVE BUT Deferoxamine INCONVENIENT PARENTERAL COMPLIANCE ONLY PROBLEMS
  • UNTIL YESTERYEARIT WAS THE ONLY TREATMENT AVAILABLE
  • IRON OVERLOAD & HEART in THALASSEMIA Serum FERRITIN maintained < 2500 µg/L ~ Cardiac DFS of 91% after 15 years HIC< 15 mg iron/g liver, dry weight, is protected from cardiac disease IT IS THE LEADING DFO from an early age ~ prevalence of heart disease CAUSE by age 15 years OF DEATH 2% INTHALASSEMIA
  • Assessment of Body Iron Burden in ThalassemiaTest CommentsIndirectSerum/plasma Ferritin Noninvasiveconcentration Lacks sensitivity and specificity Poorly correlated with hepatic iron concentration in individual patients ===============Serum transferrin Poorly correlated with hepatic ironsaturation concentration in individual patients ===============Tests of 24-h Less than half of outpatient aliquotsdeferoxamine-induced collected correctly;urinary iron excretion Ratio of stool:urine iron variable; poorly correlated with hepatic iron concentration
  • Test CommentsImaging of tissue ironCT: Liver Variable correlation with hepatic ironMRI: Liver Variable correlations with hepatic iron; cannot distinguish acceptable and dangerous ranges; imprecise if hepatic iron >20 mg/g, or if fibrosis present Only modality available to image cardiac Heart & or pituitary iron stores; correlations with Anterior Pituitary tissue iron not demonstratedEvaluation of organ Most tests lack sensitivity and specificity;function Limited information ~ functional status Reference Method. PreciseDirect Hepatic Biopsy assessment of body iron burden.Iron Quantitation Safe under US guidance.SQUID “Superconducting Noninvasive; excellent correlation withsusceptometry” biopsy-determined hepatic iron
  • MANAGEMENT OF IRON CHELATION IN THALASSEMIAS HIC HEAPTIC IRON CONCENTRATION mg iron/gm Liver Dry Weight NORMAL 3.2 to 7 0.2-1.6 7 to 15 >15 (As in (As in Heterozygous Homozygous Hemochroma- Hemochrom- tosis Patients) atosis) CardiacTo achieve this Disease level, DFO No Morbidity Hepatictoxicity will be Normal Life Fibrosis Early Death very high Expectancy
  • Hepatic Iron BurdenHomozygousHemochromatosisHIC = 7.0 – 15.0HeterozygousHemochromatosis NormalHIC = 3.2 – 7.0 HIC = 0.2 – 1.6
  • MANAGEMENT OF IRON CHELATION IN THALASSEMIAS Radiographs of cartilage Ped. Radiologist & in wrists, knees, thoraco- Endocrinologist BASELINE lumbosacral spine; bone with experience age; standing & sitting Ht. in DFO toxicity DEFER *LIVER BIOPSY BY US GUIDE ONE YEAR HIC <3.2 CHELATION *QUANTITATIVE LIVER IRONAFTER BLOOD mg/g *LIVER HISTOLOGY ReassessTRANSFUSON Dry Wt. *PCR FOR HEPATITIS C RNA HIC in 6/12 Initiate DFO HIC >3.2 25 mg/g mg/kg/night Dry Wt. X5 nights/wk
  • MANAGEMENT OF IRON CHELATION IN THALASSEMIAS II HIC <3.2 Discontinue DFO mg/g Reassess HIC Liver Dry Weight in 6 mo Biopsy assess HIC As 3.2 to 7 Continue DFO Before mg/g 25 mg/kg/night Dry Weight x 5 nights/wkYEARLYBEFORE + AGE All HIC Other Increase DFO >7 5 Tests & mg/g Dry Weight to 35 mg/kg/night x 6 nights/wk Exams (Fe/TIBC/ Severe spinal ↓DFO 25 mg/kg/night Ferritin, etc) x 4 nights/wk even if or As HIC >7 mg/g Dry Wt.; metaphyseal Before Reassess HIC in 12 mo changes
  • HIC <3.2 Discontinue DFO Liver mg/g Biopsy Dry Weight Reassess HIC in 6/12 assess HIC Continue DFO at Q As 3.2 to 7 40 mg/kg/night 18 Before mg/g x 5 nights/wk + Dry Weightmonthly All from Other HIC Tests Increase DFO age 7 to 15 to 50 mg/kg/night & mg/g5-10 yr Exams x 6 nights/wk Dry Weight (Fe/TIBC/ Ferritin, etc) As HIC > Increase DFO Before 15 mg/g to 50 mg/kg/night Dry Weight x 7 nights/wk Severe spinal or metaphyseal changes  ↓ DFO to 25 mg/kg/night x 4 nights/wk even if HIC >7; Reassess HIC in 12 months
  • HIC <3.2 Discontinue DFO Liver mg/g Biopsy Dry Weight Reassess HIC in 6/12 assess HIC Continue DFO at As 3.2 to 7 Q Before mg/g 40 mg/kg/night x 5 nights/wk 18 + Dry Weight monthly All Other HIC >10 Tests Increase DFO 7 to 15 Years & to 50 mg/kg/night mg/g Exams x 6 nights/wk Dry Weight (Fe/TIBC/ Ferritin, etc) HIC > Increase DFO As 15 to 18 mg/g to 50 mg/kg/night Before Dry Weight x 7 nights/wkHIC >18 mg/g  Consider continuous IV DFO 50 mg/kg/24 h by implantable port Severe spinal or metaphyseal changes ↓ DFO to 25 mg/kg/night x 4 nights/wk even if HIC >7; Reassess HIC in 12 months
  • Ascorbate SupplementationVitamin C supplementation may result in a markedimprovement in deferoxamine-induced iron excretionthrough expansion of the chelatable iron pool to whichdeferoxamine has access.In parallel, ascorbate-induced expansion of this poolmay aggravate the toxicity of iron in vivo.100 mg ascorbic acid should be administeredapproximately 30 to 60 minutes after initiation of aninfusion of deferoxamine, only on days during whichdeferoxamine is administered Vitamin C is given PO 100 mg/night during DFO infusion
  • Initiation of Iron Chelation WHEN? Early Chelation Early Intensive DFO before Reduces risk of 3 years hepatic fibrosis from early iron overload, prior to ↑Ferritn.Abnormal linear growth & Prevents Growth failuremetaphyseal dysplasia & Helps sexual maturation
  • DO LIVER BIOPSY ONE YEAR AFTER Regular Blood Transfusion MEASURE HIC Start DFO if >6 mg/gm Liver Dry Wt. IF BIPOSY CANNOT BE DONESTART S.C. DFO AT 25 to 35 mg/kg B.Wt. /24 hrs one year after Regular Blood Transfusion
  • Usually, patients and parents administer DFO by an overnight S.C. infusion over 8 to 12 hrs through a needle inserted into the abdomen, thigh, or upper arm.Net negative iron balance is usually maintained with 50 mg/kg body weight/night, 5 nights each week.
  • Monitoring of DFO-Related ToxicityToxicity Investigations Frequency Alteration in TherapyHigh Audiogram Yearly; if patient Interrupt DFO immediatelyFrequency symptomatic, Assess body iron burdenSensorineural immediate D/C DFO x 6 mo if HIC <3 mg/g reassessment Repeat audiogram at 3-moHearing Loss intervals until normal or stable Adjust DFO to HICRetinal Retinal Exam Yearly; if patient Interrupt DFO immediately; symptomatic, Assess body iron burdenabnormalities immediate D/C DFO x 6 mo if HIC <3 mg/g reassessment Review at 3-mo intervals until normal or stable Adjust DFO to HICMetaphyseal X-rays of wrists, knees, Yearly Reduce DFO to 25 mg/kg/d & spinal thoraco-lumbar-sacral Assess body iron burdenabnormalities spine; bone age of wrist discontinue DFO x 6 mo if HIC <3 Reassess HIC and radiographs after 6 mo; Adjust DFO to HICDecline in Determination of sitting Twice yearly Reduce DFO to 25 mg/kg/d and standing heights Assess body iron burden;height discontinue DFO x 6 mo if HIC <3velocity, Reassess HIC and radiographssitting height, after 6 mo. Adjust DFO to HIC;or both Regular (6-mo) assessment
  • 2005 Apotex DEFERIPRONE “L1” Serum Ferritin noticed to rise during therapy ?? L1 has been acknowledged to be inadequately effectivein a substantial proportion of patients in all peer-reviewed articles to have quantitated body storage iron In all of these studies, HIC have exceeded the threshold for cardiac disease and premature death in between 18% and 65% of patients after extended therapy
  • DEFERIPRONE TOXICITYRodents: Adrenal hypertrophy / gonadal & thymic atrophy, marrow atrophy and pancytopenia, growth retardation, & embryotoxicityHumans: Embryotoxicity, teratogenicity, neutropenia, and agranulocytosis Before L1 can be considered for clinical use, evaluation of its long-term toxicity in controlled clinical trials in which hepatic iron and histology are evaluated prospectively is mandatory. This step is particularly important in view of the grave prognostic implications of the progression of liver and cardiac disease in iron-loaded patients. The decision in 1999 to permit licensing of deferiprone in Europe was under legal challenge
  • 2006 DEFERIPRONE “L1” CUMULATIVE WORLDWIDE EXPERIENCE INDICATES THAT IT IS SAFE & EFFECTIVE ADVANTAGES OVER DESFERAL CAN PENETRATE CELL MEMBRANE & CHELATE TOXIC INTRACELLULAR IRON ?MORE EFFECTIVE IN REMOVING MYOCARDIAL IRON
  • DEFERIPRONE “L1”SEQUENTIAL COMBINED DESFERAL DEFERIPRONE CHELATION SHUTTLE HYPOTHESIS DEFERIPRONE CHELATES IC IRON & TRANSPORTS IT EXTRACULLARLY TO THE MORE POWERFUL DF BETTER COMPLIANCE
  • NOVARTI New Oral ChelatorS DEFERASIROX “EXJADE” A VERY PROMISING IRON CHELATOR GIVEN CONVENIENTLY ONCE DAILY INSHALLA WILL REPLACE ALL OTHER CHELATORS
  • DEFERASIROX “EXJADE”Start with 20 ug/kg/dayDissolve in a big glass of water or apple juice using a non-metallic stirrerGiven one daily preferably before mealHalf-life is around 10 hours, so once daily dose gives 24-houriron chelation from labile iron pool.Iron is excreted almost entirely through feces
  • BMT SUCCESS H/O HEPATOMEGALY OF EFFECTIVE >2 cm BCM BMT CHELATION PORTAL FIBROSISCLASS Pre-BMT OS in <16 Years DFS <16 Year Criteria (3 Year Post-BMT) (3 Year Post-BMT) I 0 90% 83% II 1-2 86% 82% III 3 62% 51%>16 Yr = III i.e. 62% i.e. 51%
  • Post-BMT Moderate 8% ACUTE GvHD CHRONIC Severe 2% ? Graft 25% Mixed Chimerism Failure R/ R/ Original Iron Overload Phlebotomy DFOCORD BLOOD TRANSPLANTATION IN UTERO TRANSPLANTATION
  • Thalassemia Intermedia 12 gm/dL Thal.Hb minor 9 gm/dL Thal. intermedia 6 gm/dL Thal. major
  • Paraspinal Temporal Bone ECTOPIC MARROW URATE NEPHROPATHY ANEMIA FEATURES FOLATEDEFICIENCY OF HYPER- THALASSEMIA SPLENISM INTERMEDIA PREGNANCY COMPLICATIONS IRON OVERLOAD LEG ULCERS GALL STONES
  • MANAGEMENT OF THALASSEMIA INTERMEDIA W&W AGGRESSIVE ? Folate Gene Therapy =========== Splenectomy Splenectomy Blood TransfusionHypertransfusion Chelation BMT
  • Malaria & Thalassemia The high frequency of theα- thalassemias and almost certainly of the β- thalassemias is areflection of heterozygote advantage against Plasmodium falciparum malaria.
  • Malaria & Thalassemiaα- thalassemia appears to enhancethe susceptibility of children toinfection with Plasmodium vivax ata time when maternal immunity may confer some protection against these infections. Thus, earlyincreased exposure to P. vivax mayact as a natural vaccine, inducingcross-species protection later inlife against the more dangerous P. falciparum.
  • In severe untreated β- thalassemia, erythropoiesis may be increased up to tenfold, of which 5% or less may be effective
  • OSTEOPENIA OSTEOPOROSIS ↓ DISABLING PAIN & # CAUSES: I.E. ENDOCRINE DESFERAL R/ CAREFUL VITAMINCHELATION D LIFESTYLE ADJUSTMENTS HORMONE ↑ Ca ↑ ACTIVITY NO SMOKING THERAPY BISPHOSPHONATE PAMIDRONATE & ZOLEDRONATE
  • HEPCIDINA SMALL PEPTIDE THAT INHIBITS IRON ABSORPTION IN SMALL BOWEL NORMALLY HEPCIDIN ↑ IN IRON OVERLOAD IN THALASSEMIA MAJOR HEPCIDIN IS INAPPROPRIATELY REDUCED HEPCIDIN IS FOUND TO BE HUMORALLY DOWNREGULATED HEPCIDIN MAY BE USED THERAPEUTICALLY
  • MAGNETIC SUSCEPTOMETRY GIVES RESULTS EVEN BETTER THAN HIC FORIRON OVERLOAD MEASUREMENT AS OF LATE 2005 ONLY 4 CENTERS IN THE WORLD HAVE THIS CAPACITY