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Thalassemia Syndrome*

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Thalassemia Syndrome* Diagnosti c A pproac h to Anemic Patients 9 Hg f =%=%9090 in 24 wk %%7070 in term %%22 in 1 year 9 HgA =16=16--2020wkwk DNA assay %5-10 in 24wk fet al %%3030 in term 9 HgA2= %1 in term %%22--33..44 in 1 year 9 Hg A /HgA2 =30 Definition Reduction in RBC mass or Hb concentration. -2SD< normal state 22..55%% of normal population= Anemic Body oxygen metabolism & accompanying CV compensation+ Hb concentration+ adjust with age & sex: Functionally anemic Definition HB (g/dl) HCT (%) MCV (µ3) Age Mean Lower Mean Lower Mean Lower (yrs) Limit Limit Limit 00..55--11..991212..551111..00373733 77 70 22--441212..551111..00383834 79 73 55--771313..001111..55393935 81 75 88--111113. 13.551212..00404036 83 76 1212--1414 Female 13.5 12.0 41 36 85 78 Male 14. 14.001212..55434337 84 77 1515--1717 Female 14. 14.001212..00414136 87 79 Male 15. 15.001313..00464638 86 78 18-49 Female 14. 14.001212..00424237 90 80 Male 16. 16.001414..00474740 90 80 Classification 11-- Physiologic Classification (Best) 22-- Red Cell Size Classification A. RBC Production Disorders (rate < expected for degree of anemii)a) B. Erythroid maturation & Ineffective erythropoesis Disorders CCoya. Hemolytic Anemia RBC Production Disorders (rate < expected fdfor degree o f anemi i)a) Marrow failure Impaired EPO production Marrow failure 1. Aplastic anemia 22.. Pure red cell aplasia 33.. Marrow replacement Marrow replacement Malignancies Osteopetrosis Myelofibrosis • vitamin D deficiency • Pancreatic insufficiency- marrow hypoplasia syndrome Impppaired EPO production • 1. Chronic renal disease 22.. Hypothyroidism, Hypopituitarism 33.. Chronic inflammation 44.. Protein malnutrition 5. HB mutants with decreased affinity for oxygen Erythroid maturation & Ineffective erythropoes is Disor ders Cyyptoplasmic maturation abnormalities Nuclear maturation abnormalities Cyyptoplasmic maturation abnormalities • Iron deficiency • Thalassemia syndrome* • Sideroblastic anemias • Lead poisoning Nuclear maturation abnormalities • Vitamin B12 deficiency • Folic acid deficiency Hemolytic Anemia • 11.. Defects of HB • a. Structural mutants • b. Synth thtietic mutant s ( ThThlalassemi a syndrome) • 22.. RBC membrane defects • 33.. Red cell metabolism defects • 44.. Antibody-Antibody-mediatedmediated Hemolytic Anemia (cont) • 5.Mechanical injury to the erythrocyte • 66.. Thermal injury to the erythrocyte • 77.. Oxidant-Oxidant-inducedinduced red cell injury • 88.. Infectious agent-agent-inducedinduced red cell injury • 99.. PNH • 10. Red cell membrane plasma-induced abnormalities Red cell Size Classification of Anemia A. Microcytic • 1. Iron Def. • 2. Chroni c Lead poisoni ng • 3. Thalassemia syndrome • 4. Sideroblastic anemia • 5. Chronic inflammation • 6. Some congenital hemolytic anemias with unstable HB Important Historical Factors Age: • NtitiNutritiona l IDA is never responsible for anemia in term infants before 6 months of age; rarely seen in premature infants prior to the time they have doubled their birth weight. • In neonatal period: recent blood loss, isoimmunization, initial manifestation of CHA or congenital infection. • First detected in 3-6 months: congenital disorder of HB synthesis or HB structure. Important Historical Factors Gender: X-linked disorders in males (G6PD- d, PKD) Race: HB S & C more common in blacks, B-Thalassemia more common in whites, α-Thalassemia trait most common among black & yellow race. Neonatal: hyperbillirubinemia: CHA, Diet: document sources of iron, vit B12, folic acid, or vit E in diet. Pica, geophagia, pagophagia=> IDA Drugs: - Oxidant-induced hemolytic anemia -Phenytoin- induced megaloblastic anemia - Drug- induced Aplastic anemia Important Historical Factors Infection: Hepatitis-induced Aplastic anemia, Infection- induced red cell aplasia or hemolytic anemia Inheritance: FH of anemia, Jaundice, Gallstones, or Splenomegaly. Diarrhea: Small bowel disease with malblabsor btion of fltfolate or vit B12. IBD with blood loss. Exudative enteropathy with blood loss. Key Physical Findings Skin HittiHyperpigmentation Fi’AiFanconi’s Anemia Petechi ae, Evans syn dro me, HUS, Purpura BM aplasia, BM infiltration Carotenemia Suspect IDA in Infants Jaundice Hemolytic Anemia, Hepatitis, Aplastic anemia Cavernous Microangiopatic Hemolytic Hemangioma anemia Ulcer on Lower S&CS & C Hbpathies, Extremity Thalassemia Key Physical Findings Facies Frontal bossing, CHA, Major Thalassemia, prominence malar severe IDA and maxillary bone Eyes MicroMicro--corneacorneaFanconi's AA TtTortuosit y of the S & C Hemogl obi nopathi es conjunctival & retinal v. MicroMicro--aneurysmsaneurysms of S & C Hemoglobinopathies retinal vessels Cataracts G6 G6PDPD--d,d, Galactosemia+ HA in newborn period Vitreous S Hemoglobinopathies hemorrhages Retinal hemorrhages Chronic, severe anemia Edema of the eyelids EBV, Exudative enteropathy+ IDA, Renal Failure Blindness Osteopetrosis Key Physical Findings Glossitis B12 B12 deficiency, IDA Mouth Angular IDA stomatitis Unilateral Poland syndrome ( increased absence of the incidence of leukemia) Chest pectoral muscles Shield chest DiamondDiamond--BlackfanBlackfan syndrome Triphalangeal Red cell aplasia thumbs Hands Hypop lasia of the Fanconi’s AA thenar eminence Spoon nails IDA Spleen Enlargement CHA, leukemia, lymphoma, acute infection, portal HTN Paraclinical Approach Initial laboratory tests: • HB & HCT • Red cell indices • Platelet count • WBC & diff • Reticulocyte count • Per iph era l blood smear Complete Blood Count Hemoglobin Hb Hematocrit Hct Mean corpuscular hemoglobin MCH MCH concentration MCHC Mean corpuscular volume MCV RBC distribution width RDW Erythrocyte count RBC Leukocyte count Plat el et count Reticulocyte count Complete Blood Count Directly measured indices: • – Hb (more reliable, more directly related to O2 carrying capacity) • – MCV • – RBC count Calculated indices: • – Hct = MCV x RBC • – MCH = Hb / RBC • – MCHC = Hb / Hct = Hb / (MCV x RBC) RDW: • Coe ffic ien t o f var iati on of th e eryth rocyt e vol ume distribution =cell size variability Coulter Counter Most widely used method. Directly measure the MCV and compute the HCT from the MCV and RBC. Cold agglutinins in high titer tend to cause sppyurious macrocytosis with low red cell counts and very high MCHCs. Warming eithhbldhdllher the blood or the diluent eliminates this problem. Red cell volume distribution width (RDW) Index of the variation in red cell size. Detect Anisocytosis.Anisocytosis. Derived from RBC histogram. RDW=SD/MCV X 100 Because RDW reflects the ratio of SD and MCV, a wide red cell distribution curve in a patient with a markedly increased MCV may still generate normal RDW. Normal range= 1111..55--1414..55 in adults For infants and children= 11..55--1515 MCV & RDW MCV RDW Low Normal High Norm Heterozygous α- normal Aplastic Anemia al and β- Thalassemia Lead poisoning High IDA Early IDA Newborn, Prematurity HB H disease Liver disease Vitamin B12B12 def. Sβ- Mixed Nutritional Folic acid def. def. Thalassemia Blood Film The singgple most useful procedure in the initial evaluation of the patient with anemia. Can be classified red cell hemolytic disorders by predominant morphology: Reticulocyte count Incceased(reased: ( RI>=3%) Chronic blood loss Hemolysis Normal or decreased: (RI=<1(RI=<1..55%)%) Impaired red cell formation Must be adjusted for the level of anemia to obtain the Reticulocyte Index: = Retic count X Patient’s HCT/Normal HCT Outline of Approach I- In itial Screeni ng & presumptive diagnosis AA-- Careful History and Physical Examination B- Initial Lab Tests Outline of Approach II- Confirmatory Studies: • Direct antiglobulin test • G6PD screening test • Osmotic fragility • HB Elec trop hores is • BMA/ biopsy • Bilirubi n, LDH, BB112, Follblilate, Haptoglobulin, Ferritin, Iron, TIBC, …. Iron Deficiency Anemia Introduction The most common nutritional deficiency in children throughout the world. High er i ncid ence i n i nf ancy. 55..55%% in schoolchildren, 5-5-88 yrs.; 22..66%% in preadolescent; 25%25% in pregnant teenage girls. Higher in black children. Inversely proportional to economic status . Introduction Iron lack the glitter of gold and silver but outshines both in biologic importance. Vital to the function of a number of critical enzymes (T). Human existence is inextricably linked to iron. Nonhematological Manifestation I. Gastrointestinal tract II. Central nervous system III. Cardiovascular system IV. Musculkllloskeletal system V. Immunologic system VI. Cellular changes VII. Other tissues Etiologic Factors (T) Dietary • Requirements • Food Iron Content Growth Blood Loss Impaired Absorption Infants at risk for IDA (T) Increased iron needs Blood loss Dietary factors Differential Diagnosis (T) Hemoglobinopathies Heme synthesis disorders caused by chemicals Sideroblastic anemias Chronic infections or other inflammatory states MliMalignancy Hereditary Orotic aciduria HypoHypo--oror Atransferrinemia Copper deficiency Inborn error of metabolism Differential Diagnosis Further evaluation in children with: • – No suspicious history of Fe deficiency • – Severe anemia • – Atypical hematological findings • – < 6mo of age • – No response to iron trial R/O blood loss, inflammation RBC count (> 5 million/ ul in thal trait) MCV/RBC ratio (<13 thal trait, >15 Fe def) Peripheral blood smear: • – Hypochromia, anisocytosis (greater in Fe deficiency) • – Poikilocytosis, target cells, cigar cells, basophilic stippling • (greater in thalassemia trait) Treatment NtitiNutritiona
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