Hydroxyurea Therapy Lowers Transcranial Doppler Velocities in Children with Sickle Cell Anemia

97 Pages·2015·2.59 MB·English

Department of Clinical Haematology/ Laboratory Services
Sickle Cell Anemia
Anthea Greenway, MBBS, FRACP, FRCPA
Dept of Clinical Haematology
The Royal Children’s Hospital
Melbourne, Australia
and
Pediatric Sickle Cell Program
Duke University Medical Centre
Durham, NC, USA
Department of Clinical Haematology/ Laboratory Services
Hemoglobinopathies
Hb A- Adult Hemoglobin
Globin gene clusters in man:
Department of Clinical Haematology/ Laboratory Services
Chromosome 11
Chromosome 16
Figure drawn by Dr. Ross Hardison, which can be found at:
<http://globin.cse.psu.edu>.
Department of Clinical Haematology/ Laboratory Services
Hemoglobin Synthesis
 Gene for beta globin is on
epsilon gamma delta beta
chromosome 11
G A
 Gene for alpha globin is on
chromosome 16
5 3
 Adult Hemoglobin (Hb A) is a2b2
’ ’
 Fetal Hemoglobin (Hb F) is a2g2
 Hemoglobin A is a2d2
2
Hb F Hb A Hb A
2
Department of Clinical Haematology/ Laboratory Services
Globin Chain Synthesis:
Thalassaemia:
Department of Clinical Haematology/ Laboratory Services
 A group of disorders characterized by a deficiency in the
synthesis of globin chains
• quantitative abnormality (reduced rate of synthesis)
• Compared with Haemoglobinopathies –inherited disorder
resulting in production of abnormal haemoglobin such as Hb E
(common in SE Asia) or SCA
 alpha or beta Thalassaemia
 Most common in persons of Mediterranean, Arabic,
Indian, Asian descent
 Severity ranges from asymptomatic to transfusion
dependent anemia
Department of Clinical Haematology/ Laboratory Services
Sickle Cell Anaemia is a multisystem disease,
associated with episodes of acute illness and
progressive organ damage, and is one of the
most common severe monogenic disorders
worldwide.
Wetherall et al, Blood 2005; 105 (921-23
Department of Clinical Haematology/ Laboratory Services
Pathophysiology of SCD:
 Mutation at sixth position of beta globin chain
changes glu → val
 With deoxygenation, the Hb S molecule polymerizes
within the RBC leading to characteristic shape
changes
 Sickled erythrocytes are rigid and obstruct small
blood vessels (VOC)→ adhesion of leukocytes→
local inflammation → disturbance in vasomotor tone
(NO)
 Sickled RBCs have a shorter half life than normal
RBCs
Department of Clinical Haematology/ Laboratory Services
Department of Clinical Haematology/ Laboratory Services
R Rees et al, Lancet 2010; 376:2018-31
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