Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1660-e1672. doi: 10.1210/clinem/dgaa936.
Klinefelter syndrome (KS) is a condition at increased risk of thrombosis compared to 46,XY men.
This work aimed to investigate the coagulation balance of KS patients by thrombin generation assay (TGA) and thromboelastometry.
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.
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.
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.
与 46,XY 男性相比，克氏综合征（KS）患者发生血栓的风险增加。
本研究旨在通过血栓生成分析（TGA）和血栓弹力描记法评估 KS 患者的凝血平衡。
本研究在意大利米兰的 3 家三级内分泌学中心进行了一项观察性、横断面研究。共纳入 58 例 KS 患者和 58 名年龄匹配的健康对照者。抗凝或抗血小板治疗以及已知的凝血障碍是排除标准。在血小板缺乏血浆（PPP）和富含血小板血浆（PRP）中进行 TGA。评估全血血栓弹力描记法和凝血因子活性。考虑到无血栓调节蛋白（ETP-TM+和 ETP-TM-）的血栓生成曲线下面积，以及它们的比值（ETP 比值），可作为促凝失衡的指标。
KS 患者的 PPP-ETP-TM+（平均 1528 比 0.1315 nM×min；P<0.001）、PPP-ETP 比值（0.78 比 0.0070；P<0.001）、VIII 因子（135%比 0.107%；P=0.001）、纤维蛋白原（283 比 0.241 mg/dL；P<0.001）和 VIII 因子/蛋白 C 比值（1.21 比 0.106；P<0.05）均高于对照组。两组的蛋白 C 水平相似。PRP 中也观察到类似的结果。KS 患者的 ETP 比值与 VIII 因子呈正相关（ρ=0.538，P<0.001）。血栓弹力描记法参数证实 KS 患者存在高凝状态。
KS 患者 PPP 和 PRP 中均存在促凝失衡，这至少部分归因于 VIII 因子水平升高。通过血栓弹力描记法证实的促凝失衡可能是这些患者发生血栓事件的原因。需要进一步研究抗血栓预防的获益/风险比。
