A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
Thromb Res. 2013 Aug;132(2):e152-7. doi: 10.1016/j.thromres.2013.07.003. Epub 2013 Aug 6.
Antithrombin (AT), protein C (PC) and protein S (PS) deficiencies are risk factors for venous thromboembolism. Overlapping values between heterozygous carriers and normal individuals often make a correct classification of a deficiency difficult. The aim of this study was to investigate the effect of sex, age, menopause and hormone therapy on natural anticoagulant plasma levels in a large group of healthy individuals, and to evaluate the need of separate reference ranges.
AT and PC were measured with a chromogenic assay, antigenic free PS with an ELISA test. To evaluate the effect of sex, age, oral contraception, hormonal status (and their interaction) on AT, PC and PS levels, linear regression models were used. Biological relevance and the value of the normal deviate z were chosen as rules to decide for separate reference ranges.
The study population consisted of 1837 healthy adult individuals (741 men, 1096 women), aged 18-85 years (median age: 44 years). In men AT levels decreased after the age of 50 years. Men had higher levels of PS than women, particularly at young ages. In women, after correction for menopause, only PC levels increased with age. Menopause affected AT and PS, but not PC levels. Oral contraceptive intake was associated with a decrease of AT and PS, and an increase of PC levels.
For AT, PC and PS, sex- and age-specific normal reference ranges can be useful, in order to better discriminate true carriers of a natural anticoagulant deficiency.
抗凝血酶（AT）、蛋白 C（PC）和蛋白 S（PS）缺乏是静脉血栓栓塞的危险因素。杂合子携带者和正常个体之间重叠的值常常使得对缺乏症的正确分类变得困难。本研究的目的是在一大群健康个体中研究性别、年龄、绝经和激素治疗对天然抗凝血浆水平的影响，并评估是否需要单独的参考范围。
使用显色测定法测定 AT 和 PC，用 ELISA 试验测定抗原性游离 PS。为了评估性别、年龄、口服避孕药、激素状态（及其相互作用）对 AT、PC 和 PS 水平的影响，使用线性回归模型。选择生物学相关性和正常偏离 z 值作为决定是否需要单独参考范围的规则。
研究人群包括 1837 名健康成年个体（741 名男性，1096 名女性），年龄 18-85 岁（中位数年龄：44 岁）。在男性中，AT 水平在 50 岁后下降。男性的 PS 水平高于女性，尤其是在年轻人群中。在女性中，绝经后，只有 PC 水平随年龄增加而增加。绝经影响 AT 和 PS，但不影响 PC 水平。口服避孕药的摄入与 AT 和 PS 的降低以及 PC 水平的升高有关。
对于 AT、PC 和 PS，可以使用性别和年龄特异性的正常参考范围，以便更好地区分真正的天然抗凝剂缺乏症携带者。
