TY - JOUR
T1 - Normal reference ranges of antithrombin, protein C and protein S
T2 - Effect of sex, age and hormonal status
AU - Franchi, Franca
AU - Biguzzi, Eugenia
AU - Martinelli, Ida
AU - Bucciarelli, Paolo
AU - Palmucci, Claudia
AU - D'Agostino, Simona
AU - Peyvandi, Flora
PY - 2013/8
Y1 - 2013/8
N2 - Introduction 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. Materials and Methods 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. Results 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. Conclusions 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.
AB - Introduction 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. Materials and Methods 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. Results 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. Conclusions 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.
KW - Antithrombin protein C
KW - protein S
KW - reference values
KW - venous thrombosis
UR - http://www.scopus.com/inward/record.url?scp=84883773716&partnerID=8YFLogxK
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U2 - 10.1016/j.thromres.2013.07.003
DO - 10.1016/j.thromres.2013.07.003
M3 - Article
C2 - 23920430
AN - SCOPUS:84883773716
VL - 132
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 2
ER -