TY - JOUR
T1 - Procoagulant Imbalance in Klinefelter Syndrome Assessed by Thrombin Generation Assay and Whole-Blood Thromboelastometry
AU - Indirli, Rita
AU - Ferrante, Emanuele
AU - Scalambrino, Erica
AU - Profka, Eriselda
AU - Clerici, Marigrazia
AU - Lettera, Tommaso
AU - Serban, Andreea Liliana
AU - Vena, Walter
AU - Pizzocaro, Alessandro
AU - Bonomi, Marco
AU - Cangiano, Biagio
AU - Carosi, Giulia
AU - Mazziotti, Gherardo
AU - Persani, Luca
AU - Lania, Andrea
AU - Arosio, Maura
AU - Peyvandi, Flora
AU - Mantovani, Giovanna
AU - Tripodi, Armando
N1 - Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2021/3/25
Y1 - 2021/3/25
N2 - CONTEXT: Klinefelter syndrome (KS) is a condition at increased risk of thrombosis compared to 46,XY men. OBJECTIVE: This work aimed to investigate the coagulation balance of KS patients by thrombin generation assay (TGA) and thromboelastometry. METHODS: An observational, cross-sectional study was conducted at 3 tertiary endocrinological centers in Milan, Italy. Fifty-eight KS patients and 58 age-matched healthy controls were included. Anticoagulant or antiplatelet therapy and known coagulation disorders were exclusion criteria. TGA was performed in platelet-poor plasma (PPP) and platelet-rich plasma (PRP). Whole-blood thromboelastometry and activities of coagulation factors were assessed. Endogenous thrombin potential (ETP), the area under the thrombin generation curve, assessed with and without thrombomodulin (ETP-TM+ and ETP-TM-), and their ratio (ETP ratio), were considered as indexes of procoagulant imbalance. RESULTS: Patients with KS displayed higher PPP-ETP-TM+ (mean 1528 vs 0.1315 nM × min; P < .001), PPP-ETP ratio (0.78 vs 0.0.70; P < .001), factor (F)VIII (135% vs 0.107%; P = .001), fibrinogen (283 vs 0.241 mg/dL; P < .001), and FVIII/protein C ratio (1.21 vs 0.1.06; P < .05) compared to controls. Protein C was comparable in the 2 groups. Similar results were observed in PRP. The ETP ratio was positively associated with FVIII (ρ = 0.538, P < .001) in KS. Thromboelastometry parameters confirmed evidence of hypercoagulability in KS. CONCLUSION: Patients with KS display a procoagulant imbalance expressed by increased thrombin generation both in PPP and PRP, which is at least in part explained by increased FVIII levels. The procoagulant imbalance, which was confirmed by thromboelastometry, may be responsible for the thrombotic events observed in these patients. Further investigation on the benefit/risk ratio of antithrombotic prophylaxis is warranted.
AB - CONTEXT: Klinefelter syndrome (KS) is a condition at increased risk of thrombosis compared to 46,XY men. OBJECTIVE: This work aimed to investigate the coagulation balance of KS patients by thrombin generation assay (TGA) and thromboelastometry. METHODS: An observational, cross-sectional study was conducted at 3 tertiary endocrinological centers in Milan, Italy. Fifty-eight KS patients and 58 age-matched healthy controls were included. Anticoagulant or antiplatelet therapy and known coagulation disorders were exclusion criteria. TGA was performed in platelet-poor plasma (PPP) and platelet-rich plasma (PRP). Whole-blood thromboelastometry and activities of coagulation factors were assessed. Endogenous thrombin potential (ETP), the area under the thrombin generation curve, assessed with and without thrombomodulin (ETP-TM+ and ETP-TM-), and their ratio (ETP ratio), were considered as indexes of procoagulant imbalance. RESULTS: Patients with KS displayed higher PPP-ETP-TM+ (mean 1528 vs 0.1315 nM × min; P < .001), PPP-ETP ratio (0.78 vs 0.0.70; P < .001), factor (F)VIII (135% vs 0.107%; P = .001), fibrinogen (283 vs 0.241 mg/dL; P < .001), and FVIII/protein C ratio (1.21 vs 0.1.06; P < .05) compared to controls. Protein C was comparable in the 2 groups. Similar results were observed in PRP. The ETP ratio was positively associated with FVIII (ρ = 0.538, P < .001) in KS. Thromboelastometry parameters confirmed evidence of hypercoagulability in KS. CONCLUSION: Patients with KS display a procoagulant imbalance expressed by increased thrombin generation both in PPP and PRP, which is at least in part explained by increased FVIII levels. The procoagulant imbalance, which was confirmed by thromboelastometry, may be responsible for the thrombotic events observed in these patients. Further investigation on the benefit/risk ratio of antithrombotic prophylaxis is warranted.
KW - hypogonadism
KW - Klinefelter syndrome
KW - testosterone
KW - thrombin generation assay
KW - thromboelastometry
KW - thrombosis
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U2 - 10.1210/clinem/dgaa936
DO - 10.1210/clinem/dgaa936
M3 - Article
C2 - 33382882
AN - SCOPUS:85103606738
VL - 106
SP - e1660-e1672
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -