Sickle Cell Anemia

40 Pages·2016·5.32 MB·English

by  Tim R. Randolph

Sickle Cell Anemia:
The Whole Story
Tim R. Randolph, PhD, MT(ASCP), CLS(NCA)
Department of Biomedical Laboratory Science
Doisy College of Health Sciences
Saint Louis University
Sickle Cell Anemia
Objectives
– By the end of this session the participants will
be able to:
Describe the molecular biology associated with the
genetic mutation and protein polymerization
Discuss abnormal lab findings associated with
sickle cell disease and trait
Discuss symptoms and treatment for patients with
sickle cell disease and trait
Thalassemias vs Hemoglobinopathies
Thalassemia Hemoglobinopathies
– Genetic mutation (435) – Genetic mutation (1065)
Globin gene(s) Globin gene(s)
– Lack of gene expression – Normal gene expression
– Decreased normal Hb – Release of abnormal Hb
Anemia Low oxygen saturation
– Low RBC, Hb, Hct, MCH, & Hb polymerization
MCHC
– Vaso-occlusion
Increased RBC divisions
Hemolysis
Smaller RBC
– Anemia
– Low MCV
– Normal MCV, MCH, &
Increases Hb/RBC MCHC
– Normalization of MCH and
MCHC
Sickle Cell Anemia
Hemoglobin S
– Definition
A genetic point mutation resulting in one nucleotide
change and a single amino acid substitution that
changes the Hgb molecule from Hgb A to Hgb S
– Etiology
Single nucleotide substitution (A >>T) resulting in
a change in one codon (GAG>>GTG) at the 6th
position on the beta gene and the substitution of a
valine (+0) for a glutamic acid (-1) at the 6th
position of the beta chain - (a b GLU>>VAL)
2 2
Sickle Cell Anemia
Sickle Cell Anemia
NORMAL
0 1 2 3 4 5 6
MET VAL HIS LEU THR PRO GLU
ATG GTG CAC CTG ACT CCT GAG
SICKLE
ATG GTG CAC CTG ACT CCT GTG
MET VAL HIS LEU THR PRO VAL

Sickle Cell Anemia
Deoxyhemoglobin S Polymer Structure
Deoxyhemoglobin S
Paired strands of deoxy Hb S
Charge and size prevent 14-stranded polymer
(crystal structure)
6b Glu from binding. (electron micrograph)
Hydrophobic pocket for 6b Val
Dykes, Nature 1978;
JMB 1979
Wishner, JMB 1975
Crepeau, PNAS 1981
Sickle cell Anemia