Thalassemia cpc
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CASE AND TOPIC PRESENTATION IN CLINICO PATHOLOGICAL CONFERENCE IN SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN

CASE AND TOPIC PRESENTATION IN CLINICO PATHOLOGICAL CONFERENCE IN SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN

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  • Listen to the mother, <br /> What are her worries? <br /> What does she think is the problem? <br /> Ask her to define her terms? <br /> Quote verbatim what she says. <br /> Understand her idioms. <br />
  • The HBB gene provides instructions for making a protein called beta-globin. <br /> When there is a mutations in the HBB gene, it prevents the production of any beta-globin. <br /> The absence of beta-globin is referred to as beta-zero (B0) thalassemia. <br /> Other HBB gene mutations allow some beta-globin to be produced but in reduced amounts. A reduced amount of beta-globin is called beta-plus (B+) thalassemia. <br />
  • HEPATOMEGALY <br /> Extra medullary erythropoiesis <br /> Iron released from breakdown of endogenous or transfused RBCs cannot be utilized for Hb synthesis – hemosiderosis <br /> Hemochromatosis <br /> Infections – transfusion related - Hep B,C, HIV <br /> Chronic active hepatitis <br /> Infection causes <br /> Poor nutrition <br /> Increased iron in body <br /> Blockage of monocyte-macrophage system <br /> Hypersplenism- leukopenia <br /> Infections associated with transfusions <br />
  • Jaundice causes <br /> Unconjugated hyperbilirubinemia - hemolysis <br /> Hepatitis - transfusion, hemochromatosis <br /> GB stones - obstructive jaundice <br /> cholangitis <br />
  • Osmotic fragility test : increased- resistance to h’lysis <br />
  • Spleenectomy <br /> Vaccination(Pneumococcal ,H. Influenzae B, Meningococcal) <br /> Prophyllactic pencillin (post spleenectomy) <br />
  • Iron-chelating agents: desferrioxamine- <br /> Dose: 30-60mg/kg/day <br /> IV / s/c infusion pump over 12 hr period 5-6 days /wk <br /> Start when ferritin >1000ng/ml <br /> Best >5 yrs <br /> Vitamin C 200 mg on day of chelation - enhances DFO induced urinary excretion of Fe <br /> Adverse effects <br /> Cardiotoxicity – arrythmias <br /> Eyes - cataract <br /> Ears - sensorimotor hearing loss <br /> Bone dysplasia-growth retardation <br /> Rapid infusion- histamine related reaction- hypotension, erythema, pruritis <br /> Infection, sepsis <br /> DEFERIPRONE <br /> Oral chelator - > 2yrs old Dose: 50-100mg/kg/day <br /> Adverse effects: <br /> Reversible arthropathy <br /> Drug induced lupus <br /> Agranulocytosis <br /> Other oral chelators <br /> Deferrothiocine <br /> Pyridoxine hydrazine <br /> ICL-670 – removes Fe from myocardial cells <br />

Thalassemia cpc Presentation Transcript

  • 1. Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 1
  • 2. A young boy known case of “beta Thalassemia Major”
  • 3. Resham kareem Roll no “354” Final year MBBS Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 3
  • 4.     Abdul Manan s/o Jamil Ahmad 6 years Resident of Kott Samaba Presented through Pediatrics Emergency on 1st Feb 2014 Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 4
  • 5.  Fever  Vomiting  Altered level of consciousness  Yellowish discoloration of eyes and urine Saturday, February 8, 2014 2 days pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 1 day 5
  • 6.  Patient is a known case of Beta Thalassemia Major diagnosed at the age of 6 months.  He was in his usual state of health 2 days back when he developed high grade fever which was sudden in onset,, intermittent and not associated with rigors and chills, flu, and cough. Fever was relieved by medication.  Fever was associated with vomiting, 2-3 times per day, vomitus was yellow in color and contained food particles but no h/o blood in vomitus. Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 6
  • 7.  He developed altered level of consciousness and irritable behavior. It was associated with drowsiness, confusion, disorientation and mood swings.  My patient developed yellow discoloration of eyes and urine , which was associated with itching and bruises. Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 7
  • 8.  There was H/O poor intake of both liquid and solid. CVS:  There is H/O breathlessness on exertion but no Edema feet or cyanosis. Respiratory system:  No H/O cough, wheezing or chest pain GUS:  There is H/O Pain in flank, dysuria, oliguria and yellow colored urine GIT  There is no H/O of diarrhea, constipation, hematemesis or melena, clay colored stool Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 8
  • 9. CNS: No H/O of fits, visual loss and weakness. Endocrine No H/O polydipsia, polyphagia, heat or cold intolerance. Locomoter system There is no H/O of joint pain, swelling and stiffness of joint. Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 9
  • 10. Diagnosis At 6 month of age diagnosed as Thalassemia Major in SZH,RYK when he presented with progressive pallor, fever and vomiting. Transfusion History Blood transfusion started from 6 months of life. First 3 years, transfusion at monthly interval Afterwards, transfusion at 15 days interval. Chelation therapy Never taken yet because of no awareness Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 10
  • 11. Pregnancy: No history of infection, drug intake, trauma or irradiation to mother Delivery: Birth by uneventful SVD in Private hospital by a doctor Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 11
  • 12. Breast feeding •Exclusively breast fed for 6 months Weaning •Started at 7th month •Contained daliya, cerelac, fruits Current diet •Home made food Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 12
  • 13. major milestones achieved Smile: 1 month Neck holding: 3 months Sitting 7 months Crawling: 10 months Standing: 1 year Walking: 15 months Talking single word: 1 year Accurate speech: 1.5 years “All milestones achieved at normal age” Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 13
  • 14. • • • • • • BCG penta 1, OPV 1, Penta 2, OPV 2, Penta 3, OPV 3, Measles I Measles II at Birth 06 wks 10 wks 14 wks 09 months 15 months Immunization status complete according to EPI schedule. Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 14
  • 15. Age of mother: 35 years Age of father: 40 years Both are confirmed cases of Thalassemia Minor Cousin Marriage 4 live siblings 1st sibling: M, 9 yrs., known case of Thalassemia Major 2nd sibling: M, 7 yrs, known case of Thalassemia Minor 3rd & 4th: twin F, 2 yrs, known case of Thalassemia Minor Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 15
  • 16. There is no other history of hereditary or infectious disease Death: 1st immediately after birth(cause unknown) 2nd spontaneous abortion at 4th month of gestation Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 16
  • 17.    Education of parents: Mother: Intermediate father: matriculation Occupation: father: shopkeeper Monthly Income: 30,000 PKR House: pukka 2 rooms locality: village sanitary condition: good Blood is donated by the blood bank of SZH,RYK Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 17
  • 18.    water supply: proper and underground Fresh water Good sanitation Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 18
  • 19. Behavior of Child: Habit and interests: Class School performance: Saturday, February 8, 2014 positive positive two good pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 19
  • 20.   Pt. received PARACETAMOL for fever in usual dose Pt. also received FURECIMIDE for oliguria Saturday, February 8, 2014 pediatric department, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan, Punjab, Pakistan 20
  • 21. EXAMINATION, 21 INVESTIGATIONS AND MANAGEMENT MUHAMMAD SALMAN ROLL NO. 314 FINAL YEAR
  • 22. Examination at the time of admission 22 6 year old child pale looking having jaundice, not oriented, irritable, drowsy & some dehydrated having vitals H/R 110/min R/R 24/min temp 102 F BP 85/60 mm of Hg
  • 23. General physical examination (current) Abdul Manan, 6 year old boy, average built, Well cooperative and well oriented in time, place and person lying comfortably in the bed. No obvious dysmorphism respiratory distress, cyanosis Pulse rate: 92/min Respiratory rate: 18/min Blood pressure: 100/65 mm of Hg Temperature: 99 F and
  • 24. Anthropometric measurements Head circumference: 51cm Height: 107cm (5th centile) Weight: 17 kg 24
  • 25. 25 • • • • • • • • • • • Pallor jaundice POSITIVE Bruises on skin THALASSEMIC FACIES clubbing koilonychias, NEGATIVE leuconychia . palmer erythema Lymph node and thyroid are not palpable. JVP not raised. Ankle and sacral edema is absent.
  • 26. GIT  26 Orodental hygiene is satisfactory with protrusion of maxillary teeth ABDOMINAL EXAMINATION  INSPECTION abdomen is distended, moving with respiration with no stria, scar mark, dilated veins. Umbilicus is central and inverted, hernial orifices are intact.  PALPATION there is no tenderness, liver is palpable 8cm below the Right costal margin in midclavicular line, firm in consistency, sharp edges, upper border is in 5th ICS with a total span of 14.4 cm. Spleen is also enlarged measuring 10cm below the costal margins , firm in consistency with sharp edges Kidneys are impalpable bimanually bladder not distended
  • 27. 27 •PERCUSSION note is resonant all over except in the region of liver and spleen, where it is dull. no shifting dullness and fluid thrill •AUSCULTATION : bowel sounds are audible, no bruit is audible.
  • 28. CVS 28  INSPECTION: apex beat is not visible, there are no pulsation, prominent veins or scar  PALPATION: apex beat is palpable in 5th intercostal space medial to mid clavicular line and is of normal character. No other sounds, thrill or left parasternal heave is palpable.  AUSCULTATION: 1st and 2nd heart sounds are of normal character with no added sound
  • 29. CNS 29 Higher mental functions are intact. Speech is normal. Cranial nerves are intact Motor and sensory systems are normal  No sign of meningeal irritation are present.  Gait is normal     GROSSLY INTACT
  • 30. Respiratory system There is normal vesicular breathing on auscultation with no added sounds.  30
  • 31. 31 INVESTIGATIONS
  • 32. Complete Blood Count  Hb: 6.9gm/dl  T.L.C: 5500/mm3  Neutophil: 77%  Lymphocyte:  Eosinophils ; 4%  monocytes:  Platelets: 18% 1% 25,000/mm3 32
  • 33. PERIPHERAL MORPHOLOGY Dimorphic picture ++  Microcytosis ++  Hypochromic, ++  anisocytosis, ++  poikilocytosis, +  target cells few  Schistiocytosis  1 NRBC/ 100 WBCs  Reticulocyte count : 3.8 %  33
  • 34. Hb electrophoresis Done at the age of 6 months Hb F: 98.1 % Hb A2: 1.9 % Hb A: 0 % 34
  • 35.  Serum ferritin level: >2000ng/ml (normal-less than 400)  Serum LFT’s: Bilirubin=9.5mg/dl ALT=1261 IU/l AST=739 IU/l  Serum alkaline phosphatase=486U/L  Serum albumin = 3 g/dl  Serum RFT’s: Blood urea= 203 mg/dl  Creatinine= 1.4 mg/dl  PT : control 18,  test 14 APTT : control 39 test 33 35
  • 36.  Serum electrolyte: Sodium=131mmol/L 36 Potassium=3.4mmol/L  ECG ----- normal  Ultrasound of abdomen: hepatospleenomegaly, PV vein size is normal  Anti HCV: positive , HbSAg: negative (result for anti HCV by ELISA awaited)  Complete urine examination : pus cell 4-6/hpf albumin + Blood sugar (random): 90 mg/dl  Thyroid function test T4 TSH 1.39ng/dl 4.41µIU/ml normal
  • 37. 37 Skull X-ray lateral view : thinning of cortex and widening
  • 38. 38 CXR ------ heart size is normal
  • 39. FINAL DIAGNOSIS BETA THALLASEMIA MAJOR WITH complications hepatic encephalopathy (stage II) Hepatorenal syndrome/ARF Hyperspleenism 39
  • 40. 40 TREATMENT GIVEN IN THE HOSPITAL RIMSHA NAZIR ROLL NO.201 FINAL YAER
  • 41.  MAINTENANCE OF ABC and monitoring of vitals  NG tube and foley catheter passed  Hydration  I/V antibiotics  Lactulose  Enema  Vit. K  Aminoglycoside through NG tube  Cimetidine  Blood transfusion 41
  • 42. TREATMENT OUTCOME 07.02.2014  Now pt. is fully conscious, co-operative, oriented in time, space and person with stable vitals.  His current investigations  LFTs bilirubin 3.7 mg/dl ALT 272 IU/L AST 129 IU/L Al.phos 326 IU/L  CBC Hb. 7.7 g/dl  RFTs urea 32 mg/dl Creatinine 0.8mg/dl  blood transfusion advised 42
  • 43. THALASSEMIA Dr. ZAHID MEHMOOD FCPS-II Resident Pediatric Dept.
  • 44. INTRODUCTION BASIC 3 TYPES •Hb A •Hb A2 •Hb F 2α + 2β 2α + 2δ 2α + 2γ 1.The α-globin genes are encoded on chromosome 16 , 2. γ, δ, and β-globin genes are encoded on chromosome 11 PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 44
  • 45. fetal period 1ST TRIMESTER HB F ,2nd trimester Hb A, 3rd trimester Hb A2 At birth appears Hb F 98% gradually decline till 6months At 6 months Hb A >95%, Hb A2 ≤3.5 %, Hb F <1.5%. •If synthesis of α chain is suppressed – level of all 3 normal Hb A (2α ,2β), A2 (2α ,2 δ),F(2α ,2γ) are reduced •If β chain is suppressed - Hb A (2α ,2β), is suppressed PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 compensatory rise in Hb F & Hb A2 45
  • 46. DEFINITION • Thalassemia syndromes are a heterogeneous group of inherited anemias characterized by reduced or absent synthesis of either alpha or Beta globin chains. • One of the most common single gene disorders ETIOLOGY • Autosomal recessive • Mutations PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 46
  • 47. CLASSIFICATION OF THALASSEMIAS • β Thalassemia • α Thalassemia • γ Thalassemia • δ Thalassemia • δ β Thalassemia • Hemoglobin Lepore syndrome • Hb C Thalassemia • Hb D Thalassemia (Punjab) • Hb E Thalassemia PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 47
  • 48. Αlpha-THALASSEMIA NO. OF GENES PRESENT GENOTYPE CLINICAL CLASSIFICATION 4 genes 3 genes 2 genes αα/αα αα/- α - α/- α αα/- - α/- - -/- - Normal Silent carrier α thalassemia trait 1 gene 0 genes or Hb H Disease Hb Barts / Hydrops fetalis PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 48
  • 49. ALPHA THALASSEMIA • Highest prevalence in Thailand • α chains shared by fetal as well as adult life. Hence manifests in both • These thalassemias don’t have ineffective erythropoiesis because β and γ tetramers are soluble chains and hence not destroyed always • Silent carrier – not identified hematologically, • Diagnosed when progeny has Hb Barts/ Hb H PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 49
  • 50. BETA THALASSEMIA PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 50
  • 51. HISTOTY Dates back over 50,000 year ago in a valley of Italy and Greece now covered by the Mediterranean. Thalassemia is a Greek word Thalassa which means the sea (Refer to the Mediterranean) emia which means “related to blood” PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 51
  • 52. EPIDEMIOLOGY Worldwide ,15million have clinically apparent thalassemic disorders About 100,000 babies worldwide are born with thalassemia each year. Globally in 2010 it resulted in about 18,000 deaths Genetic disorder of hemoglobin are the commonest single gene disorder in Pakistan. PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 52
  • 53. THALASSEMIA IN PAKISTAN In Pakistan the disease is seen in almost all the parts of country, with an estimated carrier rate of 5-8% ( About 9.8 million carriers in total population) Approximately 4000-5000 beta thalassemia children are born each year. Average life expectancy in Pakistan is 10 years. At present disease load is around 100,000 patients throughout the country. PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 53
  • 54. THALASSEMIA IN RAHIM YAR KHAN (SZH) Total thalassemic patients registered in SZH,RYK are 160 Total admissions 14433 2013 Thalassemia PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN 1335(9%) Saturday, February 8, 2014 54
  • 55. β/ β Normal CLASSIFICATION OF Β THALASSEMIA CLASSIFICATIO GENOTYPE N CLINICAL SEVERITY β thal minor/ trait β / +, β β/ 0 β Silent β thal intermedia β + / +, β β +/ 0 β Moderate β thal major β 0/β 0 Severe PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 55
  • 56. PATHOPHYSIOLOGY • Since ẞ chain synthesis reduced - 1. gamma 2‫ ץ‬and delta δ2 chain combines with normally produced α chains ( Hb F (α2 2‫ , )ץ‬Hb A2 (α2 δ2) - Increased production of Hb F and Hb A2 2. Relative excess of α chains → α tetramers forms aggregates → precipitate in red cells → inclusion bodies → premature destruction of maturing erythroblasts within the marrow (Ineffective erythropoiesis) or in the periphery (Hemolysis)→ destroyed in spleen PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 56
  • 57. PATHOPHYSIOLOGY….. continued Anemia result from lack of adequate Hb A → tissue hypoxia→ ↑ EPO production → ↑ erythropoiesis in the marrow and sometimes extramedullary → expansion of medullary cavity of various bones Liver spleen enlarge → extramedullay hematopoiesis PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 57
  • 58. IRON OVER LOAD Causes •Hemolysis •Increased hematopoiesis •Increased absorption from GIT •Repeated blood transfusion PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 58
  • 59. ACCUMULATION OF IRON • Deposition in pituitary - endocrine disturbance - short stature, delayed puberty, poor sec. sexual characteristics • Hemochromatosis - cirrhosis of liver • Cardiomyopathy (cardiac hemosiderosis) -cardiac failure • Deposition in pancreas -diabetes mellitus • Lungs: restrictive lung defects • Adrenal insufficiency • Hypothyroidism, hyperparathyroidism • Increased susceptibity to infections (iron favours bacterial PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN growth) espc : Ye rs inia infections Saturday, February 8, 2014 59
  • 60. CLINICAL FEATURES INFANTS: • Age of presentation: 6-9 mo (Hb F replaced by Hb A) • Progressive pallor and jaundice • Cardiac failure • Fever • Hepatomegaly • Splenomegaly PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 60
  • 61. CLINICAL FEATURES BY CHILDHOOD: Severe anemia-cardiac dilatation Jaundice Transfusion dependent Changes in skeletal system  Growth retardation PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 61
  • 62. SKELETAL CHANGES THALASSEMIC FACIES Frontal bossing, maxillary hypertrophy, depression of nasal bridge , Malocclusion of teeth PARAVERTEBRAL MASSES: • • • • • Broadening of ribs at costo-vertebral attachment Paraparesis PATHOLOGICAL FRACTURES: Cortical thinning Increased porosity of long bones DELAYED PNEUMATISATION OF SINUSES - sinusitis PEDIATRIC DEPARTMENT, SHEIKH ZAYED PREMATURE FUSION MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, OF EPIPHYSES - Short PUNJAB, PAKISTAN stature Saturday, February 8, 2014 62
  • 63. CLINICAL FEATURES (THALASSEMIA INTERMEDIA) • Moderate pallor, usually maintains Hb >6gm% • Anemia worsens with pregnancy and infections (erythroid stress) • Less transfusion dependant • Skeletal changes present, progressive splenomegaly • Growth retardation • Longer survival than Thalassemia major PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 63
  • 64. CLINICAL FEATURES (THALASSEMIA MINOR) • Usually ASYMPTOMATIC • Mild pallor, no jaundice • No growth retardation, no skeletal abnormalities, no splenomegaly • MAY PRESENT AS REFRACTORY IRON DEFICIENCY ANEMIA (Hypochromic microcytic anemia) • Unresponsive/ refractory to Fe therapy • Normal life expectancy PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 64
  • 65. DIAGNOSIS BLOOD PICTURE •Hb – reduced (3-9mg/dl) •RBC count – increased •WBC, platelets – normal, PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 65
  • 66. PERIPHERAL BLOOD PICTURE • RBC indices – MCV & MCH,MCHC reduced • microcytic hypochromic anemia, anisopoikilocytosis, target cells, nucleated RBC, leptocytes, basophilic stippling, tear drop cells • Cytoplasmic incl bodies in α thal • Post splenectomy : Howell-Jolly and Heinz bodies • Reticulocyte count increased (upto 10%) but Relative Reticulocytopenia PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 66
  • 67. • Total. Bilirubin & Indirect. bilirubin – increased • B.M. study: hyperplastic erythropoiesis PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 67
  • 68. Hb ELECTROPHORESIS Beta Thalassemia Major Hb F: 98 % Hb A2: 2 % Hb A: 0 % PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 68
  • 69. X ray skull: “ hair on end” appearance or “crew-cut” appearance PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 69
  • 70. IRON OVERLOAD ASSESSMENT • S.Ferritin • Urinary Fe excretion • Liver biopsy - standard • Myocardial-liver MRI indexes PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 70
  • 71. TREATMENT • Supportive Treatment • Psychological/social support • Blood Transfusion • Chelation Therapy ( For iron overload) • Surgical • Bone marrow transplant • Newer therapy PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 71
  • 72. SUPPORTIVE TREATMENT • Vitamin C – increases iron excretion • Restrict Fe intake – decrease meat, liver, spinach • Folate – 1 mg/day • Genetic counselling • Psychological support • Hormonal therapy – GH, estrogen, testosterone, thyroxin PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 72
  • 73. PSYCHOLOGICAL/SOCIAL SUPPORT • WISH • BLOOD DONATION • MORAL SUPPORT • CHELATION THERAPY PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 73
  • 74. BLOOD TRANSFUSION • BT at 4-6 wks interval Packed RBC, leucocyte-poor • Hb to be maintained – (Hb >10.5 gm/dl) • If regular transfusions and chelation - no hepatomegaly, no facies • 10-15ml/kg RBC raises Hb by 3-5gm/dl – PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 74
  • 75. CHELATION THERAPY • ( 1 unit of blood contains 250 mg iron) • DESFERRIOXAMINE • DEFERIPRONE • DEFERASIROX PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 75
  • 76. BONE MARROW TRANSPLANTATION • • • • • Severely affected child Minimum transfusions No iron toxicity Age usually < 5 years HLA identical donor (sib) • Risk factors: Hepatomegaly >2cm Portal fibrosis Iron overload Older age • Success rate In low risk young patients, the 5yr thalassemia free survival rate is 73 -94% at National Institute of Blood Disease & Bone Marrow PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Transplantation, Karach Saturday, February 8, 2014 76
  • 77. SURGICAL TREATMENT - SPLENECTOMY • Deferred as long as possible. At least till 5-6 yrs age • Spleenectomy (indications): • Hyperspleenism (spleenomegaly+mono/bi/pancytopenia) • Massive splenomegaly causing mechanical discomfort • Progressively increasing blood transfusion PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 requirements (>180-200 ml/kg/yr) packed RBC 77
  • 78. NEWER THERAPIES • GENE MANIPULATION AND REPLACEMENT • Hb F AUGEMENTATION • Hydroxyurea • Myelaran • Butyrate derivatives • PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 78
  • 79. PRENATAL DIAGNOSIS • β/α ratio: <0.025 in fetal blood – Thal. major • Chorionic villous biopsy at 10-12 wks • amniocentesis at 15-18th wk gestation Analysis of fetal DNA • PCR to detect β globin gene PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 79
  • 80. PREVENTION: • Preventing marriage b/w traits • Antenatal diagnosis • Termination of pregnancy if Thalassemia major PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 80
  • 81. COMPLICATIONS • Hypersplenism ------- surgery • Bleeding Diathesis--- FFP • Hemosiderosis ------- chelation therapy • Hepatitis and hepatic encephalopathy • Pathological Fractures • Growth Retardation • Diabetes Mellitus • Failure to attain Puberty • Complications of Repeated Blood Transfusions PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 81
  • 82. COMPLICATIONS….. continued • Repeated infections • Cardiac complications (Anemia , Hemosiderosis) • Pericarditis • Arrythmias • Heart Block • CCF PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 82
  • 83. • • • • • • • • • • • MANAGEMENT OF HEPATIC ENCEPHALOPATHY MAINTENANCE OF ABC and monitoring of vitals and protein restriction NG tube and foley catheter passed Gastric lavage if malena or haemetemesis I/V antibiotics for infection Lactulose to change gut flora Enema for constipation Hydration Vit. K Oral Aminoglycoside / Metronidazole H2 blocker/ PPI PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Blood transfusion if there is anemia Saturday, February 8, 2014 83
  • 84. HEPATORENAL SYNDROME • Hepatic failure, hypernatremia, hypokalemia, oliguria, deranged RFTs • Two types type 1 – acute type II -- chronic • Withdrawal of nephrotoxic drugs • Renal function recovers if hepatic function improves PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 84
  • 85. WHAT WE CAN DO FOR THIS PATIENT FURTHER • Chelation therapy • Hb F augmentation • Spleenectomy and vaccination • Bone marrow transplantation • Prevent other complications of thalassemia PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 85
  • 86. CAUSES OF DEATH IN THALASSEMICS • The most common cause of death in older children was heart disease(cardiomyopathy) followed by infection &liver disease. • While in younger children infections outnumber the cardiac complications. PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 86
  • 87. KEY MESSAGE •Prevention is better than cure • Better to prevent thalassemia. • IF not, Better to prevent complications of thalassemia. • How: By monitoring patients clinically & by investigations in PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN order to detect earlier ,so intervention can be done. Saturday, February 8, 2014 87
  • 88. W HAT W AIM FOR THALASSEMIA E PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN  Saturday, February 8, 2014 88
  • 89. .  It was like a dream come true for 12-year old Naima Gul, resident ofFebruary 8, 2014 Swat, 89 when Saturday, Mingora, she became the first female pilot of the Pakistan. PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN
  • 90. PEDIATRIC DEPARTMENT, SHEIKH ZAYED MEDICAL COLLEGE/HOSPITAL, RAHIM YAR KHAN, PUNJAB, PAKISTAN Saturday, February 8, 2014 90