Hyacinth Harding-Goldson, Marvin Reid & Richard Augier - Uwi.edu

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U W I R E S E A R C H F O R D E V E L O P M E N T 2 0 1 3
T R O P I C A L M E D I C I N E R E S E A R C H I N S T I T U T E
D E P A R T M E N T O F S U R G E R Y , R A D I O L O G Y , A N A E S T H E S I A & I N T E N S I V E C A R E
Hyacinth Harding-Goldson,
Marvin Reid & Richard Augier
Urinary Leukotriene E4 in
Patients with Homozygous
Sickle Cell Disease

U W I R E S E A R C H F O R D E V E L O P M E N T 2 0 1 3
Sickle populations cell in disease tropical predominantly and sub-tropical affects
and their descendants in the Americas Africa leukotriene
Europe but also occurs in populations from and which E4 (LTE4) is a metabolic by- product
of can be measured in the urine. Discovery
the Jamaica Mediterranean, has a relatively the Middle high East, prevalence and India. E4 an association between urinary leukotriene
sickle cell disease (SCD), which accounts for of support (uLTE4) levels and acute painful crisis would
disease the use of uLTE4 as a biomarker of
1:150 genetic births variation (approx 300/year). which there It is is an production inherited of severity (in terms of frequency of episodes
possible APC) and therapy use for of APC. leukotriene inhibitors as a
of The abnormal haemoglobin haemoglobin S molecule S in crystalises red blood when cells. Pain
exposed in a conformational to low oxygen change concentrations in the shape resulting be affects all persons with the disease. It can
blood cells from their normal biconcave, round of red chronic acute, chronic or acute on a background of
a pain and often is severe as to have
shape increased to crescents fragility of called the red ‘sickling’. blood cells, This increased results lives. destructive socio-economic impact on their
episodes People who suffer from frequent painful
destruction results in a and low a shortened red blood life cell span. count The called latter missing are often stigmatized because of often
pain- work or school and requiring strong
anaemia. blood vessels Sickling with also impaired causes blood blockage supply. of There small acute relieving drugs. Approximately 50 cases of
Sickle painful crisis are managed monthly at the
is from also damage inflammation to their of lining the blood and activation vessels resulting at cell unit and another 30 cases are seen
body’s immunological/hormonal stress response. of the Casualty the University Hospital of the West Indies
healthcare Department, placing additional
Blockage starved of of oxygen blood vessels, resulting leads in tissue to tissues death being overburdened requirements service. on an already
more commonly in severe and debilitating pain. but Presently that there is only one treatment
Patients painful crises with (APC). sickle cell These disease involve suffer the extremities, from acute of can reduce the frequency
drug acute painful crisis, and this
pelvis, leukotrienes abdomen, (CysLT) chest are inflammatory and back. molecules Cysteinyl patients, cannot be used in all
for so the search
produced 5-lipooxygenase from pathway. arachidonic There acid is evidence through that the continues. other treatments
CysLT- of occlusion related of vascular blood effects vessels may in SCD. be the Cysteinyl cause
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A method biomarker of measuring that could be the used severity as an of objective
and the level of pain would allow for disease
targeted care, and help to reverse common more
misperceptions. useful in improving Such the a standard tool would of care be extremely
to persons with sickle cell disease available
extension the quality and productivity and of their by
lives. the inflammatory This project molecules investigates Cysteinyl the possibility leukotrienes that
(CysLT) could be one such biomarker.
Cysteinyl have been leukotrienes
in the pathophysiology implicated
of constriction asthma. They of cause
pulmonary blood the
vessels, mucous secretion increase
and vascular permeability. pulmonary
The the association discovery has of
resulted leukotriene in the inhibitors use of
in asthmatic management patients. of
A related demonstrated painful episodes association and uLTE4 between will suggest sicklea
in possible SCD patients, application and allow of leukotriene for measurement inhibitors
the relationship between dose and effect. This of
would of leukotriene allow for inhibitors future investigations as therapy for into sickle the use
pain.
cell
This concentration experimental in patients study investigates with homozygous uLTE4
sickle no pain cell and disease during during painful periods episode. when It comprises they have
of three phases:
Phase An experimental 1
patients with homozygous study comparing SCD during uLTE4 steady in
state controls. with age and gender matched HbAA
Phase An 2
study experimental
steady state comparing
of uLTE4 in levels
groups of patients two
with SCD. Group homozygous
with a history 1, those
“high frequency” of of a
APCs and group (>5/year, 2, those high)
who frequency” have (

Collaborators: Professor UWI, Mona. Marvin Reid, Director, Sickle Cell Unit,
Dr Services, Susanna Sickle Bortolusso-Ali, Cell Unit, UWI, Director Mona. Clinical
Dr Jennifer Knight-Madden, Sickle Cell Unit, UWI.
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