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

12 th Congress of the European Hematology Association
Considering the whole observation time elevated sP-selectin was associated
with a hazard ratio for thrombosis of 2.0 [95% confidence interval:
0.5-8.2, p=0.34] adjusted for age, sex, oral anticoagulation and positive
thrombosis history in multivariate cox regression analysis. Conclusions.
Elevated sP-selectin levels were associated with past thrombosis and
thrombosis within the first year after sP-selectin determination in LApatients,
whereas it was not associated with thrombosis after five years
of follow-up. Whether high p-selectin levels qualify as a predictive parameter
for thrombosis in LA-patients needs confirmation.
0879
P-SELECTIN GENE HAPLOTYPES MODULATE SOLUBLE P-SELECTIN LEVELS
AND CONTRIBUTE TO THE RISK OF VENOUS THROMBOEMBOLISM
C. Ay, L.V. Jungbauer, A. Kaider, S. Koder, S. Panzer, I. Pabinger,
M. Mannhalter
Medical University Vienna, VIENNA, Austria
Background. The cell adhesion molecule P-selectin, which mediates
the interaction of activated platelets or endothelial cells with leukocytes,
is central to the pathogenesis of thrombosis. In arterial and venous
thromboembolism (VTE) increased soluble P-selectin (sP-selectin) levels
have been found, and associations of P-selectin genotypes with thrombotic
disease have been discussed. Aims. The aim of our study was to
assess the effect of certain haplotypes in the P-selectin gene comprising
single nucleotide polymorphisms (SNPs) in the promotor region and
SNPs in the coding region altering amino acids (SNPs C-2123G, S290N,
N562D, T715P). Methods. We conducted a case-control study of 116
high risk patients with a history of objectively confirmed recurrent VTE
and at least one event of an unprovoked deep venous thrombosis or
pulmonary embolism. One-hundred-twenty-nine age- and sex-matched
healthy individuals served as controls. The SNPs -2123 (C>G), S290N
(G>A), N562D (A>G) and T715P (A>C) were analyzed by allele-specific
PCR. The genotype results were used for computer-assisted haplotype
construction. sP-selectin (ng/mL) was measured by ELISA. The difference
in the haplotype distribution between patients and controls was
described by logistic regression models. Differences in P-sel levels were
analysed using linear regression models. Results. In patients (53 women;
mean age ±SD:56±12 yrs) nine haplotypes and in controls (66 women;
mean age ±SD:53±11 yrs) ten haplotypes were identified. Failure for
haplotyping occurred in three controls. Six haplotypes in patients and
seven in controls had a frequency of above 5% and together they covered
93% and 96% of the genetic variation, respectively. Compared to
haplotype-6 (CGAA, major allele at all positions) odds ratios for VTE
were 2.1 (95% CI: 1.1-4.3) for haplotype-2 (GGAA) and 4.8 (2.1-12.0)
for haplotype-8 (CAGA). Statistical analysis showed that haplotypes
were significantly associated with sP-selectin levels (p