Discussion
The level of Hemoglobin F expression is one of the most important
modifiers of sickle cell disease .HbF values influence clinical
symptomatology both in children and adults. Increase in value of HbF has
been associated with fewer number of veno-occlusive crisis ,fewer
episodes of acute chest syndrome and reduced early mortality .
Pharmacological intervention using HU induces HbF production.
Hydroxyurea is a recommended treatment strategy in sickle cell disease.
Multiple clinical trials have proven its efficacy in reducing morbidity
and improving quality of life .
Affordable access to hydroxyurea is well established in state of Odisha
in India. In the population we surveyed every patient was taking
hydroxyurea more or less regularly, as reported by himself. The delivery
is at times hampered because, some patients ,find even the small travel
distance unmanageable. Regularity is challenge because of social-
patient related issues, which need redressal
HU dosing rationalization (fixed dosing ) is standard clinical practice
and may defer from recommended dosing guidelines. The criterion of using
mild myelosuppression as dosing guide ( has never been utilized. Fixed
dose HU had been previously reviewed
HUSTLE (NCT00305175) is a prospective observational study with a primary
goal of describing the long-term clinical effects of hydroxyurea
escalated to maximal tolerated dose (MTD) in children with SCA. In 230
children, providing 610 patient-years of follow up, the mean attained
HbF% at MTD was >20% for up to 4 years of follow-up. When
HbF% values were ≤20%, children had twice the odds of hospitalization
for any reason (P < .0001), including vaso-occlusive
pain (P < .01) and acute chest syndrome (ACS)
(P < .01), and more than four times the odds of
admission for fever (P < .001). Therefore, attaining
HbF >20% was associated with fewer hospitalizations
without significant toxicity. These data support the use of hydroxyurea
in children and suggest that the preferred dosing strategy is one that
targets a HbF endpoint >20%. According
to a 2014 expert panel report sponsored by the National Heart, Lung, and
Blood Institute on the evidence-based management of SCA, HU therapy
should be offered to all children as young as 9 months of age,
regardless of symptom
In this analysis, HbF levels increased in every individual and were more
than desired level of 20 %. The change was seen all across population ,
irrespective of age and gender. In a short group of higher age group the
increase in HbF appeared to be even more striking, This observation
needs further study and could be result of longer usage of HU, because
of higher age group.
The achievement of desired HbF
target levels using “real-world” scenario, compels us to think about
HU strategies. The practice of using fixed dose schedules, in real-time
clinical practice, with minimal follow up deserves a serious discussion
and could be of great use in low resource countries. Probably this
cohort of real-world scenario proves effectiveness of this strategy
which is feasible, manageable, well tolerated , beneficial and covers
for the not well trained health personnel.