ECE2020 Audio ePoster Presentations Reproductive and Developmental Endocrinology (79 abstracts)
Coagulation abnormalities in patients with klinefelter syndrome compared to age-matched healthy controls: Cross-sectional assessment by thrombin generation test
Rita Indirli 1,2 , Eriselda Profka 2 , Walter Vena 2,3 , Biagio Cangiano 2,4 , Alessandro Pizzocaro 3 , Marco Bonomi 2,4 , Marigrazia Clerici 5 , Erica Scalambrino 5 , Gherardo Mazziotti 3,6 , Andrea Lania 3,6 , Maura Arosio 1,2 , Giovanna Mantovani 1,2 , Armando Tripodi 5 & Emanuele Ferrante 1
1Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy; 2University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy; 3Humanitas Clinical and Research Center, Endocrinology, Diabetology and Andrology Unit, Rozzano (MI), Italy; 4IRCCS Istituto Auxologico Italiano, Division of Endocrine and Metabolic Diseases and Lab. of Endocrine and Metabolic Research, Milan, Italy; 5Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and Fondazione Luigi Villa, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy; 6Humanitas University of Milan, Department of Biomedical Sciences, Milan, Italy
Introduction: Klinefelter syndrome (KS) is known to be associated with an increased risk of venous thromboembolism and arterial thrombosis, but the aetiology behind this prothrombotic status has not been fully elucidated. The aim of this study was to cross-sectionally investigate the coagulative state in subjects with KS compared to age-matched healthy males.
Methods: Coagulation factors assessment, clinical characteristics collection and thrombin generation test (TGT) were performed in 58 consecutive KS patients and 58 controls. TGT is based on the continuous registration of thrombin generation (mediated by procoagulants) and decay (mediated by anticoagulants) using a fluorogenic substrate. The curve of thrombin concentrations (vertical axis) by time (horizontal axis) is called thrombogram and is described by the following parameters: lag-time (time from coagulation ignition to the formation of the first amounts of thrombin); thrombin-peak and time-to-peak; endogenous thrombin potential (ETP, the area under the thrombin curve, measured with and without the addition of thrombomodulin); the ETP-ratio (ETP with/ETP without thrombomodulin), that may be considered the best parameter through which in vivosubtle procoagulant imbalance can be detected.
Results: No statistically significant difference was found between KS patients and healthy subjects in lag-time, thrombin-peak, time-to-peak or ETP; however, the ETP-ratio was significantly higher in KS compared to controls (0.73 and 0.66 respectively, P < 0.001). KS patients had higher circulating concentrations of Factor VIII (P = 0.001) and Fibrinogen (P < 0.001) and a higher Factor VIII/Protein C ratio (P = 0.018), while platelet count, PT ratio, aPTT ratio, Factor II, Protein C and Antithrombin were similar in the two groups. ETP-ratio was positively correlated with Factor VIII concentrations (P = 0.007, ρ = 0.355) and showed a trend of association with impaired fasting glucose (P = 0.069) and Factor VIII/Protein C ratio (P = 0.072, ρ = 0.240). Fibrinogen levels were positively associated with age (P = 0.004, ρ = 0.401), body mass index (P = 0.001, ρ = 0.468) and fasting plasma glucose (P = 0.049, ρ = 0.356), while FVIII did not show any correlation with metabolic parameters as well as age. Testosterone replacement therapy and smoke were not associated with any of the coagulation parameters.
Conclusion: As clinically suggested, a procoagulant imbalance is present in KS subjects and is possibly related to higher Factor VIII concentrations here demonstrated. While testosterone replacement therapy and smoking habit did not show a significant impact, other typical factors associated with thrombotic risk such as advanced age, BMI and altered glucose metabolism could further increase this imbalance by determining hyperfibrinogenemia.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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