12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
5'year period (2002-2006). During the years 2002-2006, a total of 1375
couples were screened and counseled for haemoglobinopathies in our
thalassemia prevention unit. In 811 couples (58,9%) both partners had
no problem, in 416 (30,2%) only one partner was a carrier of thalassemia
or other haemoglobinopathy and in 148 (10,7%) both partners carried
an abnormal gene. The pregnancies at-risk involved 100 couples that
were identified through preconception and prenatal carrier screening,
while few had a positive family history or were identified during pregnancy.
Prenatal diagnosis was mainly carried out by chorionic villus
sampling (CVS) at 11-12 weeks of gestation, and in few cases by amniotic
fluid sampling collected at 16-18 weeks. Very few late comers were
tested by fetal blood sampling at 20-24 weeks of gestation. 77 couples
were at risk for a β-thalassaemic child, 19 couples for sickle-cell/ β-thalassaemic
child and 2 for sickle cell disease. 3 couples had more than one
pregnancy. From 100 chorionic villous biopsies and amniocentesis and
subsequent DNA analysis of the samples, 26 fetuses were found to be
homozygous or double heterozygotes, and termination of the pregnancy
was advised. 74 were either carriers (heterozygous) or non-carriers
of either mutation that was found in both parents, and the pregnancies
continued. In three cases of twin pregnancies selective abortion of the
two affected fetuses was indicated. Among the couples screened various
and rare combinations were detected. We found combinations of βthalassaemic
carriers with ‰β, Lepore, HbD, Hb O-Arab, HPFH, Hb
Osu Christianborg and Hb E-Saskatoon. Combinations of HbS carriers
with β-thalassemia, ‰β, HbD, Lepore, and E- Saskatoon were also
encountered. In one couple in which both partners carried O-Arab mutations
and in another where both carried HbE, prenatal diagnosis was not
performed since homozygosity is not clinically severe. 5 couples were
immigrants, Albania (2), Nigeria (1) Romania (1) and Bangladesh (1).
The Greek population that was screened came from all over Northern
Greece. The thalassaemia prevention program is successful and prenatal
diagnosis is mandatory in at-risk couples. This Thalassemia prevention
program has decreased effectively the incidence of severe thalassaemia
in our country, and today the very rare cases of homozygous thalassemia
that are born is due to couples that fail to use the National
Thalassemia Prevention Program for one reason or other.
0797
HYDROXYUREA TREATMENT OF SICKLE CELL DISEASES CAUSES MEGALOBLASTIC
TRANSFORMATION OF THE BONE MARROW THAT IS RESPONSIBLE FOR THE INCREASE
OF THE MEAN CORPUSCULAR VOLUME
A.C. Silva-Pinto, R.C. Carrara, V.C. Oliveira, P.V. Palma,
A.D. Campos, M.A. Zago, D.T. Covas
University of S. Paulo, RIBEIRAO PRETO, Brazil
Background. The positive impacts of hydroxyurea (HU) treatment on
the clinical course and the survival of patients with sickle cell diseases
are now well documented. Several clinical trials have demonstrated the
efficacy of HU in reducing the frequency and intensity of the vaso-occlusive
crises. An increase of the mean corpuscular volume (MCV) is the
hematological parameter that correlates better with the clinical improvement
and for this reason is most often used to monitor the therapeutic
efficacy of HU. The mechanism whereby HU raises the MCV is still
unclear. Aims.Our hypothesis is that HU increases the MCV because it
causes megaloblastic transformation of the bone marrow cells by its
effects on the ribunucleotide reduction. Materials and Methods. The
study included 20 sickle cell anemia patients under regular follow-up
(group 1: 10 patients taking 10-30 mg HU/kg/day; group 2: 10 patients
not receiving HU), and 10 bone marrow donors as controls (group 3). All
patients were taking folic acid supplementation. Samples of peripheral
blood (1 mL) and bone marrow (1 mL) were collected from all participants
for morphometrical evaluation of cells in bone marrow smears and
measurements of adhesion molecules expression by flow cytometry.
The study was approved by the institutional research review committee,
and the patients signed an informed consent. Results. Bone marrow
smears from the group 1 patients showed many signs of megaloblastic
transformation, such as megaloblasts, red cells with open chromatin
nuclei, hypersegmented neutrophils, giant metamyelocytes and hypersegmented
megakaryocyte nuclei. Signs of megaloblastic transformation
were rare in group 2 and absent in the control group. The morphometric
data demonstrated an increase of the mean cell surface area of all
cell types studied of group 1 compared with group 2 or group 3, especially
of erythroid precursors (Table 1). Flow cytometry showed a statistically
significant reduction (p