Clinical Hematology II - Higher Colleges Of Technology

Clinical Hematology II HML2143 1 1 LO1: Describe the hemoglobinopathies with particular regard to their prevalence and importance in the UAE. Week 3: Describe the clinical effects of the interactions between thalassemia and the hemoglobin variants....

Clinical Hematology II HML2143 1 1 LO1: Describe the hemoglobinopathies with particular regard to their prevalence and importance in the UAE. Week 3: Describe the clinical effects of the interactions between thalassemia and the hemoglobin variants. 2  “Other Hb Variants and Thalaseemia like conditions”  Other Types Of Hb Variants “Qualitative” Types of single amino acid substitution in hemoglobinopathies (molecular determinants of other qualitative variants): 1. Hb S (β 6 Glu → Val) 2. Hb C (β 6 Glu → Lys) 3. Hb E (β 26 Glu → Lys) 4. Hb D Punjab (β 121 Glu → Gln) 5. Hb O Arab (β 121 Glu→ Lys) 6. Hb G Philadelphia (α 68 Asn→ Lys)  Hemoglobin C: Hb C (Β 6 Glu → Lys) Pathophysiology: Genetic defect→ Decrease in Hb solubility → Crystals formation of Hb C→ RBCs become rigid & destroyed in the spleen Blood film: Target cells, folded & irregular contracted cells Homozygous: > 90% Hb C & slight ↑ Hb F (not more than 7%) Hb C trait: *Asymptomatic→ No hematological abnormalities except target cells in blood smear. (60-70) % is Hb A & (30-40) % Hb C Hemoglobin D: Hb-D Punjab (Β 121 Glu → Gln) Hb D molecules do not sickle Have normal solubility properties Both homozygous & heterozygous are asymptomatic (Benign) No hematological abnormalities but occasionally there is an increase in target cells  Hemoglobin E: Hb E (β 26 Glu → Lys) Common in SE Asia Homozygous: resulted in mild hemolytic anemia with target cells. Trait: asymptomatic Note: The most common β-chain hemoglobin variants (Hb S, Hb C): 1. In trait→ the abnormal Hb usually accounts < 50% of total Hb So we will have: (60% Hb A & 35-40% Hb S or Hb C) 2. In homozygous state, the abnormal Hb constitutes 90-95% of total Hb  Hemoglobinopathies Double heterozygosity: (Compound heterozygosity): The inheritance of one abnormal gene from each parent. 1. Hb SC→ combines between Hb S from one parent & Hb C from other parent 2. Hb SD→ combines between Hb S & Hb D 3. Hb S/β-Thalassemia→ clinical picture resembles homozygous sickle cell disease 4. Hb E/ Thalassemia Compound heterozygosity of Hb E & thalassemia (α or β) Moderate to severe anemia similar to thalassemia major So, managed as thalassemia  Hb M (Met Hemoglobin) Pathophysiology: Amino acid substitution may cause: → Stabilization of heme iron in the ferric state (Fe+3) → Forming met-hemoglobin → cannot bind oxygen. Hb M gives a brownish color to the blood. Hb M level is rarely > 30%. The patients appear to be cyanotic  Other Thalassemia Like Conditions: 1) Hb Constant Spring Pathogenicity: α-chain is elongated by 31 a. a.→ so it reduces α production→ unstable Hb→ α thala like 1) Homozygous: Hb Constant Spring 2) Heterozygous: → Asymptomatic Hb F & A2 normal, Hb CS & Hb A  2) Hereditary Persistence of Fetal Hb (HPFH) → δ β-thalassemia Pathogenicity: Both β & δ are defective → Impair production of Hb A & Hb A2 Homozygous→ Only Hb F is produced (100% Hb F) Heterozygous → Hb F: 10-30% increases Hb A2: 1-1.5 % decreases Hb A: the rest  3) Hb Lepore Pathogenicity: Unequal crossing over of globin genes → Hybrid globin chain of δ globin from one end fused with β globin at the other end Homozygous → like β-thala intermedia Hb Lepore (8 -30) % & Hb F the remaining Heterozygous → Silent carrier (Hb lepore 10%) Hb A 80-90%  References McKenzie, Shirlyn/ Landis-Piwowar; Kristin/ Williams, Lynne (2019). Clinical Laboratory Hematology. 4th Ed. Pearson Education. ISBN 9780134709239 Kaushansky/ et al, (2016) Williams Hematology, 9th Ed. McGraw-Hill. ISBN 9780071833011 Lewis, S., Bain, B., Bates, I. (2012) Dacie and Lewis, Practical Haematology, 11th Ed., Churchill Livingstone Elsevier. ISBN: 978-0-7020-3407-7 Hoffbrand, A., Moss, P. (2011) Essential Haematology, 6th Ed. Wiley Blackwell. ISBN: 978-1-4051- 9890-5 Moss, Paul, Pettit, Hoffbrand. Essential Haematology, 5th Ed. Blackwell Science. 2006. ISBN: 9781405136495 Moore, Gary/ Knight, Gavin (2013) Essential Haematology, Oxford University Press ISBN: 9780191666711 800 MyHCT (800 69428) [email protected] www.hct.ac.ae Happiness Center PO Box 25026 Abu Dhabi, UAE HCT_UAE hctuae 14