Hypochromic Anaemias
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1 Hypochromic Anaemias Dr Mere Kende MBBS, MMED (Path), MAACB, MACTM, MACRRM LECTURER-SMHS
2 Anaemia LOW HEMOGLOBIN
3 Anaemia Definition: Hb <lower Limit of reference range for age Age 24hrs months months months years 115 LL of normal Range (g/l) >12 years girls 120 boys 130
4 Changes in Hb after Birth [Hb] at birth: g/L. Hb g/l It rises transiently in the first 24 hours Slowly falls to as low as 95 g/l by the 9 th week. By 6 months, Hb stabilises at around 125 g/l, the lower end of the adult range, Then increases towards adolescence Birth 24hours 3months 6months adult
5 Age related References
6
7 Blood Film
8 Hypochromia Iron Deficiency Comment on this blood film from an elderly male complaining of undue tiredness.
9 Causes: Classification based on MCV
10 Iron Deficiency Thalassaemia Sideroblastic Anemia Lead Poisoning
11 Iron is Essential Component of Hb
12 Porphyrin Pathway Pyrrole ring
13 Iron Deficiency Iron deficiency is the most common cause of anemia worldwide. Aside from circulating red blood cells, the major location of iron in the body is the storage pool as ferritin or as hemosiderin and in macrophages.
14
15 Absorption: stomach, duodenum, and upper jejunum. Diet iron: heme is efficiently absorbed (10 20%), Nonheme iron less so (1 5%) Loss ---approximately 1 mg/d are normally lost through exfoliation of skin and mucosal cells. There is no physiologic mechanism for increasing normal body iron losses.
16
17 Menstrual blood loss -50 ml/month Women must absorb 3 4 mg of iron from the diet each day. Menorrhagia risk of iron deficiency; must supply extra iron
18 Causes of iron deficiency. Deficient diet (infants <1y cow milk) Decreased absorption (worm) Increased requirements Pregnancy Lactation Blood loss (common) Gastrointestinal (PUD/aspirin) Menstrual Blood donation Hemoglobinuria Iron sequestration Pulmonary hemosiderosis
19 Iron Deficiency Anaemia Commonest cause of anaemia throughout the world May be subclinical -role cognitive and psychomotor development Leads to anaemia in those with severe deficiency Present in 10-30% of children in high risk groups Most due to inadequate dietary intake Lost through cow milk provoked GIT loss in infants/worm infestation & menstruation in adolescent girls
20 Children at High Risk for iron Deficiency Anaemia Group/Age Additional Risk Factors mechanism <6months Prematurity Inadequate Stores LBW/Multiple Births Maternal iron deficiency 6-24months Exclusively Breastfed Inadequate Intake Delayed introduction of iron containing food Excessive Cow milks Adolescent Females Menstrual loss Poor Diet Rapid Growth Spurt Socially Disadvantaged Worm Infection Fad diets/ Vegeterians Poor diet Inadequate Intake
21 Clinical Findings Symptoms and Signs Anemic symptoms: easy fatigability, tachycardia, palpitations and tachypnea on exertion. Severe deficiency causes skin and mucosal changes, including a smooth tongue, Cheilosis (fissures at the corners of the mouth) koilonychia (spooning of the fingernails)/brittle nails. Dysphagia because of the formation of esophageal webs (Plummer Vinson syndrome) also occurs. Pica, craving for specific foods (ice chips, etc) often not rich in iron.
22 Koilonykia (spooning of nail)
23 Pallor
24 Pallor
25 Jaundice
26 Hemoglobinuria
27 Glossitis-Megaloblastic/Iron Deficiency
28 Cheilitis/Beefy Red Tongue
29 Laboratory Findings Iron deficiency develops in stages. Microcytic hypopchromic anemia Serum ferritin less than 30 mcg/l is a highly reliable indicator of iron deficiency. Elevated TIBC Elevated transferrin Decrease % saturation MCV low Severe cases: anisocytosis, poikilocytosis, target cells, pencil shaped cells Occasionally nucleated red cells Platelet count is commonly elevated Elevated soluble transferrin receptor
30 Blood Film/FBE hypochromic Microcytic Low MCV
31 Stages of Iron Deficiency
32 Differential Diagnosis Thalassemia (high iron/ferritin) Sideroblastic anemia. (increased iron/ferritin) Chronic Inflammatory Condition Myelodyspasia
33
34 Essentials of Diagnosis Serum ferritin < 12 mcg/l. Caused by bleeding in adults unless proved otherwise. Responds to iron therapy
35 Treatment Therapeutic trial of iron replacement. Identify & Treat cause especially a source of occult blood loss Oral iron tablets IM injection response in 2 months Continue treatment for 3-6 months to replenish stores
36 Thalassemia
37 Hemoglobinopathies Thalassaemia Sickle Cell Disease Unstable Haemoglobins
38 Thalasaemia Normal HbA1 ( 2 2) <2% HbA2 ( 2 2) Individuals inherit one beta gene from each parents compared to 2 alpha genes Alpha thalassemia- alpha chain defect/gene deletion - Thalassemia-beta chain defect/reduced beta chain amount/qantitative defect
39 Thalassaemia Inheritance Chrom 6 & 11
40 Alpha Thalassaemia Syndromes -Globin Syndromes Haematocrit MCV genes 4 Normal Normal 3 Silent carrier Normal 2 Thalassemia minor 28 40% fl 1 Hb H disease ( 2 2) 22 32% fl 0 Hydrops fetalis/hb Barts stillbirths
41 Thalassaemia Major (inadequate -chain) Marked relative excess of alpha chain Uncommon in 1 st world due to increased antenatal screen & prenatal termination Present during second 6 months of life [switch of HbF ( 2 2) - HbA1 ( 2 2) at 1 st 6months] Presentation: severe hemolytic anaemia, slow growth, skeletal deformities, hepatosplenomegaly (always), heart failure hypochromic, microcytic anaemia, PCV <20%
42 Gamma to Beta switch
43 Beta Thalassemia syndromes. -Globin Genes Hb A Hb A 2 Hb F Normal Homozygous 97 99% 1 3% < 1% T. Major Homozygous 0 0% 4 10% 90 96% T. Major Homozygous % 4 10% 90 96% T. Intermedia Homozygous % 0 10% 6 100% T. Minor Heterozygous % 4 8% 1 5% Heterozygous % 4 8% 1 5%
44 Marked erythroblastosis & bizzare RBC forms on Blood Film Increased HbF ( 2 2) and 2-fold increase in HbA2 ( 2 2) Depend on transfusion Reduced life expectancy Iron Overload Genetic Counselling/Antenatal diagnosis Bone Marrow Transplant
45 Thalassemia minor /thalassemia trait very common Rarely show significant anaemia and symptoms Causes microcytic, hypochromic Anaemia Clues on FBE include elevated RBC count/marked microcytosis Diagnosis: Hb electrophoresis- elevated HBA2 Often treated unnecessarily with iron HbA2 levels may be corrected with iron therapy obscuring the dx
46 AT /Trait is 1 or 2 gene deletions relatively common in Asian populations Asymptomatic throughout life Microcytosis /target cells may be seen Hb electrophoresis normal except decreased HbA2
47 HbH 3 gene deletions microcytic but asymptomatic when well May develop anaemia when stressed Heinz Body seen Hb Barts -4 alpha gene deletions hydrops fetalis at birth Incompatible with life
48
49 Prenatal Diagnosis (DNA analysis)- CVS/AFS
50 Essentials of Diagnosis of Thalassaemia Microcytosis out of proportion to the degree of anemia. Positive family history or lifelong personal history of microcytic anemia. Abnormal red blood cell morphology with microcytes, acanthocytes, and target cells. In -thalassemia, elevated levels of hemoglobin A 2 or F.
51 Differential Diagnosis Iron deficiency Low Iron Low Ferritin Blood Film not strikingly abnormal (less target cells, acanthocytes etc) Hb electrophoresis-normal
52 Hb Electrophoresis -Globin Genes Hb A Hb A 2 Hb F Normal Homozygous 97 99% 1 3% < 1% T. Major Homozygous 0 0% 4 10% 90 96% T. Major Homozygous % 4 10% 90 96% T. Intermedia Homozygous % 0 10% 6 100% T. Minor Heterozygous % 4 8% 1 5% Heterozygous % 4 8% 1 5%
53 Microcytic (Low MCV) Serum Ferritin Normal Hb Electrophoresis Low Iron Deficiency Thalassaemia minor
54 References Current Medical Diagnosis and Treatment 2008 LG. Gomella, SA. Haist; Clinicians Pocket Reference 11 th Edition 2007 Harrison s Text of Medicine 17 th Edition
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