Increased platelet reactivity in Klinefelter men: something new to consider.

Abstract

Patients with Klinefelter syndrome (KS) exhibit an increased cardiovascular risk, but underlying mechanisms are largely unknown. The present cross-sectional study has been conducted to evaluate platelet reactivity and the expression of platelet activation markers (8-iso-prostaglandin F2α[8-iso-PGF2α] and 11-dehydro-thromboxane-B₂[11-dehydro-TXB2]) in KS patients and healthy controls. Twenty-three consecutive KS patients under testosterone replacement therapy have been included as case group and 46 age-matched healthy males recruited among hospital staff served as controls. Light transmission aggregometry was performed in both cases and controls and maximal platelet aggregation (max-A%) was defined as maximal light transmittance reached within 5min after the addition of 0.2 or 0.4mm arachidonic acid (AA). A≥50% irreversible light transmittance (LT-50%) following platelet stimulation defined an adequate platelet aggregation and AC-50% was defined as the minimal agonist concentration needed to achieve LT-50%. The AC-50% was 0.26mm AA for KS and 0.36mm for controls (p<0.001). Whereas AA (0.2mm) induced LT-50% in 69.6% of KS and in 15.2% of controls (p<0.001), the stimulation with AA (0.4mm) determined LT-50% in all cases and controls. However, max-A% was higher in KS than in controls both after AA (0.2mm) (65.61% vs. 46.30%, p=0.002,) and after AA (0.4mm) (96.43% vs. 81.04%, p<0.001). 8-iso-PGF2α and 11-dehydro-TXB2 were higher in KS than in controls (446.54pg/mg creatinine vs. 230.00pg/mg creatinine, p<0.001 and 1278.36pg/mg creatinine vs. 595.08pg/mg creatinine, p=0.001, respectively) and AC-50% inversely correlated with 8-iso-PGF2α (ρ=-0.548, p<0.001) and with 11-dehydro-TXB2 (ρ=-0.523, p<0.001). In a linear regression model, KS independently predicted a lower AC-50% (β=-0.597, p<0.001) and higher levels of 8-iso-PGF2α (β=0.709, p<0.001) and 11-dehydro-TXB2 (β=0.605, p<0.001). In contrast, no correlation has been found between max-A%, testosterone and estradiol levels in KS. We observed increased platelet reactivity in KS. This might, at least in part, explain the increased thrombotic risk associated with this disease.