[绝经后女性中与活化蛋白C表型抵抗相关的血栓形成倾向综合征]
[Thrombophilic syndrome associated to phenotypic resistance to activated protein C in postmenopausal women].
作者信息
Caserta L, Caserta R, Torella M, Perricone F, Nesti E, Sessa M, Tagliaferri A, De Francesco F, De Lucia D, Panariello S
机构信息
Dipartimento di Scienze Ginecologiche, Ostetriche e della Riproduzione, Laboratorio di Emostasi e Trombosi, II Università degli Studi di Napoli, Naples, Italy.
出版信息
Minerva Ginecol. 2004 Apr;56(2):131-6.
AIM
Hormone replacement therapy (HRT) may reduce the risk of cardiovascular events in healthy postmenopausal women. However recent studies suggest a 2-4 fold increased risk of idiopathic venous thromboembolism (VTE) among users of HRT. Our aim was to evaluate the overall effect of HRT on hemostatic variables probably related to increased VTE risk reported in epidemiological studies.
METHODS
Therefore, 100 healthy postmenopausal women aged 45-60 years divided into 50 HRT non-users and 50 HRT users were examined. The authors assayed on the automated coagulometer ACL7000 (Instrumentation Laboratory, Milan) the procoagulant proteins: factor VIII (VIII:C) and factor VII (VII:C); the natural anticoagulant proteins: antithrombin (ATIII), protein C (PC), protein S (PS) and the resistance to anticoagulant action of activated protein C (APC-Resistance). The free tissue factor pathway inhibitor (TFPI) was measured with an ELISA method (Diagnostica Stagò; France, Roche). The in vivo coagulation and fibrinolysis activation was evaluated by the assays of prothrombin fragment 1+2 (F1+2) and plasmin- antiplasmin complexes (PAP) using ELISA techniques.
RESULTS
Increased levels of FVIII:C and FVII:C were observed in HRT users and HRT non-users women compared to controls (FVIII:C= 126+/-58%, 120+/-59% vs 85+/-15% p=0.0001; FVII: C 113+/-23%, 103+/-19% vs 90+/-16% p=0.0001). The activation peptides were significantly different compared to those found in control subjects; higher values were observed in HRT users compared to HRT non-users (F1+2=1.11+/-0.44 nM, 077+/-0.31 nM vs 0.45+/-0.35 p=0.00001; P-AP= 606+/-406 ng/ml, 514+/-205 ng/ml vs 235+/-59 p=0.0001). The ATIII and the PC were similar among the 3 different groups of subjects, but reduced levels of PS were observed in HRT users (PS 93+/-23%, 105+/-22% vs 109+/-12 p=0.0001). The mean normalized APC sensitivity ratio (APC-SR) was lower in the two populations of women as compared with that of controls (nAPC-SR 1.02+/-0.7, 1.02+/-0.8 vs 1.1+/-25 p=0.02). The values of free TFPI were reduced in HRT users compared to HRT non-users (9.1+/-1.9 ng/ml, 10.1+/-2.3 ng/ml vs 4.6+/-1.5 ng/ml p<0.0001).
CONCLUSION
HRT appears to be associated to a shift in the procoagulant-anticoagulant balance towards a procoagulant state. The changes in hemostatic system could explain the increased risk of VTE in healthy postmenopausal women during HRT, nevertheless this risk could be higher in women known to have a congenital or acquired thrombophilic state.
目的
激素替代疗法（HRT）可能会降低健康绝经后女性发生心血管事件的风险。然而，最近的研究表明，HRT使用者发生特发性静脉血栓栓塞（VTE）的风险增加了2至4倍。我们的目的是评估HRT对止血变量的总体影响，这些变量可能与流行病学研究中报道的VTE风险增加有关。
方法
因此，对100名年龄在45至60岁之间的健康绝经后女性进行了检查，将她们分为50名非HRT使用者和50名HRT使用者。作者在自动凝血仪ACL7000（仪器实验室，米兰）上检测促凝血蛋白：凝血因子VIII（VIII:C）和凝血因子VII（VII:C）；天然抗凝血蛋白：抗凝血酶（ATIII）、蛋白C（PC）、蛋白S（PS）以及对活化蛋白C抗凝作用的抵抗性（APC抵抗）。采用ELISA方法（Diagnostica Stagò；法国，罗氏）测量游离组织因子途径抑制剂（TFPI）。使用ELISA技术通过检测凝血酶原片段1+2（F1+2）和纤溶酶-抗纤溶酶复合物（PAP）来评估体内凝血和纤溶激活情况。
结果
与对照组相比，HRT使用者和非HRT使用者女性的FVIII:C和FVII:C水平均升高（FVIII:C = 126±58%，120±59% vs 85±15%，p = 0.0001；FVII:C 113±23%，103±19% vs 90±16%，p = 0.0001）。与对照组相比，活化肽有显著差异；与非HRT使用者相比，HRT使用者的值更高（F1+2 = 1.11±0.44 nM，0.77±0.31 nM vs 0.45±0.35，p = 0.00001；P-AP = 606±406 ng/ml，514±2o5 ng/ml vs 235±59，p = 0.0001）。3组不同受试者的ATIII和PC相似，但HRT使用者的PS水平降低（PS 93±23%，105±22% vs 109±12，p = 0.0001）。与对照组相比，这两组女性的平均标准化APC敏感性比值（APC-SR）较低（nAPC-SR 1.02±0.7，1.02±0.8 vs 1.1±25，p = 0.02）。与非HRT使用者相比，HRT使用者的游离TFPI值降低（9.1±1.9 ng/ml，10.1±2.3 ng/ml vs 4.6±1.5 ng/ml，p<0.0001）。
结论
HRT似乎与促凝血-抗凝血平衡向促凝血状态的转变有关。止血系统的变化可以解释健康绝经后女性在HRT期间VTE风险增加的原因，不过，已知患有先天性或获得性血栓形成倾向状态的女性，这种风险可能更高。
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