Points to be discussed:  Definitions  Patho-physiology  Signs & Symptoms  Diagnosis  Options of management.  Complications  Preventive measures  Long term follow up of patients

DEFINITIONS  THALASSEMIA MAJOR  THALASSEMIA INTERMEDIA  THALASSEMIA MINOR, TRAIT, HETEROGENOUS

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An example of inheritance: Marriage between two carriers

Developmental expression of the globin chains  Embryonic hemoglobins        Fetal hemoglobins   HbF  Adult hemoglobins   HbA2   HbA

Three Normal Hemoglobins  Hb A  2  2 96%  Hb A2  2  2 3%  Hb F  2  2 1%

THALASSAEMIA An abnormality associated with one  gene is called  -thal minor (  Tm). An abnormality associated with two  genes is called  -thal major (  TM).  chain production may be decreased or absent resulting in excess free  chains. If production is decreased we refer to the phenotype as  +, if absent  o.

HAEMATOLOGICAL PROFILE B T Minor HbN-Dec RCCInc (Marrow compensating for ineffective haematopoiesis MCV Dec  MCH Dec  Hypochromasia+ Anisocytosis++ (Microcytes) PoikilocytosisTarget Cells+ Immature FormsPolychromasia Coarse basophilic stippling

 Mentzer: MCV = if <13 thal minor RBC >13 then iron deficiency  Shine - Lal: (MCV) 2 X MCH = if 1530 then iron deficiency  England- Frazer : MCV- (Hgb X 5)- RBC- 3.4 = if negative : thal minor positive : iron def

Hb. ELECTROPHORESIS  HbA:Present  HbF:N-Slightly Inc (Only compensating for 1 chain)  HbA2:Inc (4-5%, reason unknown but this feature is used diagnostically differentiating from  TM or  TM)

 TM  0 b 0 – most severe – no  chain production.  0 b + - moderately severe – some  chain production.  +  + - Increased HbF with normal or elevated HbA 2 – there is remained HbA. Clinical severity varies accordingly.

CLINICAL ASPECTS  Hepatomegaly and splenomegaly.  Chronic haemolysis that may be accompanied by gallstones, gout and icterus (jaundice).  Not usually detected until 6 months of age.  Excess iron from blood transfusions may lead to cardiac and hepatic problems.  As with other haemolytic anaemias, more iron is absorbed from the gut exacerbating iron overload.  Largely overcome by the use of Desferroxamine.

HAEMATOLOGICAL PROFILE HbDec Anisocytosis+++ (Macrocytes, Microcytes) PoikilocytosisTarget cells +++ Tear drops Schistocytosis Acanthocytes, Howell Jolly Bodies, Target Cells (post splenectomy) Immature FormsPolychromasia ++ Nucleated RBC +++ (bone marrow response)

Blood Film - BTM

X-RAYS IN THAL. PTs

Transfusional Iron TRANSFUSIONAL IRON OVERLOAD IN THALASSEMIA Thalassemia Centre, Dept. of Pediatrics University of Turin, Italy Hepatic Fibrosis --> Cirrhosis Cardiac arrhythmia Hypogonadism Diabetes Hypothyroidism Hypoparathyroidism Death Cardiac Failure

Blood Transfusion mg iron/kg/day Blood Transfusion mg iron/kg/day IRON ACCUMULATION IN TRANSFUSION-DEPENDENT ANEMIAS In a 50 kg person  mg/day In a 50 kg person  mg/day Iron Excretion (Urine & Feces) 1-2mg/day Iron Accumulation mg/day Iron Accumulation mg/day

Management  Medical /Nursing management  Social and Behavioral management  Management of complications  Compliance

Medical Management  Blood Transfusion-----Dr. Khawla  Chelation Therapy---- Dr Ahmad  Bone Marrow Transplant  Gene Therapy

TRANSFUSION CARE OF THE CHILD WITH THALASSEMIA MAJOR  Transfusion ≥ Hb 9.0 g/dl  Extended red cell genotype  Match donor blood to ABO, rhesus and Kell  filter or wash blood – (white cell depletion)  Vaccinate with hepatitis B Pre-tX  Transfusion ≥ Hb 9.0 g/dl  Extended red cell genotype  Match donor blood to ABO, rhesus and Kell  filter or wash blood – (white cell depletion)  Vaccinate with hepatitis B Pre-tX Red Blood Cell Transfusion:

Bone Marrow Transplant  HLA matched Donor  Preparation of the patient  Consider selection criteria  Stem cells could be collected by:  Bone Marrow Aspiration  Peripheral apheresis  Cord Blood

24 When

COMPLICATIONS  Cardiac  Endocrine  Hepatic  Renal  Skeletal  Virus transmission  Blood reactions.

Transfusional Iron TRANSFUSIONAL IRON OVERLOAD IN THALASSEMIA Thalassemia Centre, Dept. of Pediatrics University of Turin, Italy Hepatic Fibrosis --> Cirrhosis Cardiac arrhythmia Hypogonadism Diabetes Hypothyroidism Hypoparathyroidism Death Cardiac Failure

CROSS-SECTIONAL STUDY OF 342 PATIENTS IN THE NIH-SPONSORED THALASSEMIA CLINICAL RESEARCH NETWORK REGISTRY* Reference: Adapted from Cunningham, et al. Blood. Online Feb. 26, 2004 DOI % (30/128) 23% (30/128) 5% Cardiac Disease (req. meds) 9% 1% Hypoparathyroidism 17% 8% Thyroid Disease 21% 9% Diabetes Mellitus 62% 41% Hypogonadism (req. meds) 25+ yrs (n=129) 25+ yrs (n=129) yr (n=93) yr (n=93) Age Group

B-THAL. INTERMEDIA

Adapted from B. Modell and V. Berdoukas, 1984 THALASSEMIA MAJOR – SURVIVAL

Prevention Premarietal Screening Prenatal diagnosis Pre Implantation Genetic Diagnosis