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

enerca@enerca.org

I am grateful to :Dora Bachir (France)Beatrice Gulbis (Belgium) Lucia di Franceschi (Italy) Pere Gascon (Spain)