Is
there
a rationale
for
treatment
of
sickle
cell anemia, except
for
acute
complications?
NO, but…JL Vives CorronsRed Cell
Pathology
Unit
Hospital Clnic. University
of
BarcelonaHead
of
ENERCA
Project
EUROPEAN CENTRES FOR HAEMOGLOBINOPATHIES
UKFRANCEBELGIUMGERMANYITALYSPAINPORTUGALGREECE
EUROPEAN NETWORK FOR
RARE AND CONGENITAL ANAEMIAS
Catalan
Network for
Major
Haemoglobinopathies
EUROPEAN NETWORK FOR
RARE AND CONGENITAL ANAEMIAS
ENERCA RECOMMENDATIONS FOR SICKLE CELL DISEASE
American Journal of Haematology , 2010
In preparation , 2012
The
modern
management
of
sickle
celldisease
(SCD) is
based
on
three
therapeutic
approaches:
1. Blood
transfusion
2. Penicillin
3. Hydroxyurea (HU)
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
HU has specific indications in SCD, but
Not everyone with SCD should take HU as preventive therapy
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
PRINCIPLE 1
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
The
use
of HU
is indicated
in SCD patients
with
one
or more
of the
following
problems
•Frequent
painful
episodes•History
of acute
chest
syndrome
(ACS)
•History
of other
severe
vasoocclusive
crisis (VOC)•Severe
symptomatic
anemia
•Very
young
childrenGriffin
P. Rodgers
(2012)
Specific
therapies
for sickle-cell
disease
We
should
make
every
effort
to treat
children
and adolescents
with
SCA before
they
develop
chronic,
inexorable, and
ultimately
fatal organ
damage.
HU appears
to be the
best available
treatment option
in symptomatic
patients
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
PRINCIPLE 2
HbF
Induction
Improve
RheologyImprove
Rheology
Reduce Haemolysis
Physiological
beneficial effects
of
HU
Clinical
beneficial effects
of
HU
1.
Reduces frequency of VOC ad ACS2.
Reduces haemolysis and anaemia
3.
Improves organ damage in adults (*)4.
Prevents cerebrovascular
disease(**)
(*)
Acute
Chest
Syndrome
(ACS)(**)
Stroke
(*) Russell E. Ware. Blood 2010 115: 5300-5311Evidence of effectiveness of HU treatment
(3 year
)
Indication of long term HU administration (up to 8 years) should follow the principle of “personalized treatment”
designed for each patient according to
the clinical severity and the molecular phenotype
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
PRINCIPLE 3
For “personalized treatment”
one
must
consider:
A‐
First
line
treatment
B‐
Second
line
treatment
D‐
Prevention
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
B. Gulbis , Belgium Protocol for the treatment of SCD
Consensus
criteria
for
initiating
treatment
with
HU in patients
(> 24 months) with
HbSS
or
HbS/β0‐thal
(*)
1. Frequent
Pain
crises
,including
dactylitis2. Acute
Chest
Syndrome
(ACS) and
vasoclussive
crisis (VOC)
3. Severe
chonic
anaemia
(hypoxemia)
4. Elevated
Trans
cranial
doppler
(TCD) velocity
and
its
indication
of
cronic
transfusion5. Low hemoglobin
F (HbF)
6. High
WBC and
Lactic
dehydrogenase
FIRST LINE TREATMENT WITH HU
(*) Russell E. Ware. Blood 2010 115: 5300-5311
1. Children
(>2 Years) & Adults
(Severe
pain
& anaemia, VOC, ACS)
Treatment
with
HU (initial
dose
15mg/Kg/day)
2. Very
young
children
(< 2 years) (all
clinical
situations)
Treatment
with
HU
(initial
dose: 20mg/Kg/day)
3. Children
& adults
with
minimal
disease
activity
No treatment
FIRST LINE TREATMENT WITH HU
G.P. Rodgers .Specific Theapies for SCD,2012
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
However, Some haematologists feel uncomfortable managing SCD adult patients with HU
because:
1. Does not decrease the number of hospitalizations for VOC and ACS
2. Does not reduce transfusion requirements3. It is cytotoxic4. It creates uncertainties (effect on spermatogenesis and oncogenesis)
Therefore
efectiveness
of
HU in clinical
practice
has notalways
been
realized.
UNCERTAINTIES OF LONG TERM HU TREATMENT
Myelosupression
(resolve by decreasing dosage or temporally interruption of administration). Decreased reticulocytes
and
Hb, PMN and platelets count.
Incidence on men fertility ( inform the patient , sperm freezing)
In case of pregnancy occurrence, stop HU treatment immediarely)
Decreased of reticulocytes, Hb, neutrophil
and PLT count
Occurrence or recurrence of leg ulcer ( skin protection, avoid trauma or cold creams)
Melanonychia, dry skin (inform the patient)
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
Barriers
to Hydroxyurea Treatment
(*)
1. Patients
2. Parents/family
3. Health
providers
4. System
(*) US.National
Institute
of
Health. Consensus
Conference
(2007)
No clear
consensus
for
Hydrea
treatment(require
a case‐
by‐
case decission)
1.
Conditional
Trans
cranial
doppler
(TCD) velocities2.
Abnormal
brain
MRI (eg, silent
infarcts)
3.
Neurocognitive
or
neurosensorial decline4.
Age
< 24 months
5.
Poor
growth
and
development6.
Parental request
7.
High
HbF8.
SCD genotype
(*) Russell E. Ware. Blood
2010 115: 5300‐5311
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
HU
should no be given
to patients with high HbF, except in cases with severe complications
PRINCIPLE 4
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
IMPORTANCE OF SCD genotype
• No indication for HU treatment in children
• Some indications in adults with stroke or severeneurosensorial involvement
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
CLINICAL SEVERITY OF SCD GENOTYPES
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
CLINICAL SEVERITY AND SCD GENOTYPES
NEWBORN SCREENING IS AN IMPORTANT TOOL FOR PREDINCTING INDIVIDUAL
COMPLEX SCD PHENOTYPES AND DESIGN A PERSONALIZED RATIONALE FOR
TREATMENT IN CHILDREN
Long‐term side‐effects of Hydrea
administration such as increased risk of malignancy and reduced fertility, should be cause of concern when
prescribing the drug for young children, who may take it for decades.
PRINCIPLE 5
Is
there
a rationale
for
treatment
of
sickle
cell
anemia except
for
acute
complications?
THANK YOU!
Red Cell
Pathology
Unit
Hospital Clinic
i Provincial
University
of
Barcelona
c/ Villarroel 170
080036‐Barcelona
Phone: +34 934515950
I am grateful to :Dora Bachir (France)Beatrice Gulbis (Belgium) Lucia di Franceschi (Italy) Pere Gascon (Spain)