title: 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 5 min after the addition of 0.2 or 0.4 mm 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 0.26 mm AA for KS and 0.36 mm for controls (p < 0.001). Whereas AA (0.2 mm) induced LT-50% in 69.6% of KS and in 15.2% of controls (p < 0.001), the stimulation with AA (0.4 mm) determined LT-50% in all cases and controls. However, max-A% was higher in KS than in controls both after AA (0.2 mm) (65.61% vs. 46.30%, p = 0.002,) and after AA (0.4 mm) (96.43% vs. 81.04%, p < 0.001). 8-iso-PGF2α and 11-dehydro-TXB2 were higher in KS than in controls (446.54 pg/mg creatinine vs. 230.00 pg/mg creatinine, p < 0.001 and 1278.36 pg/mg creatinine vs. 595.08 pg/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.
authors.affiliation: Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.|Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: M N D
authors.initials: MN
authors.lastname: Di Minno
authors.affiliation: Department of Cardiothoracic and Respiratory Sciences, Endocrine Unit, Second University of Naples, Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Esposito
authors.affiliation: Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Minno
authors.affiliation: Department of Cardiothoracic and Respiratory Sciences, Endocrine Unit, Second University of Naples, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Accardo
authors.affiliation: Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Lupoli
authors.affiliation: Department of Medical Traslational Sciences, University Federico II, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cittadini
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic Sciences and Geriatrics, Second University of Naples, Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Giugliano
authors.affiliation: Department of Cardiothoracic and Respiratory Sciences, Endocrine Unit, Second University of Naples, Naples, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pasquali
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D002318:Cardiovascular Diseases; D003404:Creatinine / Q000378:metabolism; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D006801:Humans; D007713:Klinefelter Syndrome / Q000097:blood*; D008297:Male; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000502:physiology*; D012307:Risk Factors; D013739:Testosterone / Q000097:blood / Q000627:therapeutic use; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C075750:8-epi-prostaglandin F2alpha; D013739:Testosterone; D004958:Estradiol; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine; D015237:Dinoprost
keywords: Klinefelter syndrome; cardiovascular risk; platelet hyper-reactivity; testosterone