{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T03:02:22Z","timestamp":1767841342641,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Antithrombin (AT), protein C (PC), and protein S (PS) are natural anticoagulant proteins that deficiency in each of them is associated with an increased risk of venous thromboembolism.The overlapping of plasma levels of AT, PC, and PS between healthy individuals and heterozygote carriers poses significant challenges in precise diagnosis. This study aimed to evaluate the effect of most influencing variables on plasma levels of these proteins and propose specific reference intervals to improve the interpretation of the laboratory results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study was conducted on 1464 individuals who were referred to Massoud medical laboratory, Tehran, Iran, from 2019 to 2020. AT and PC were measured through chromogenic assay and PS plasma level with the clot\u2010based assay. A multivariable linear regression model was performed to evaluate the effect of sex, age, oral contraceptive (OCP) intake, and menopause state. Normal deviate z value was used for different subgroups to justify the need for a separate reference interval.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>1200 verified healthy individuals (434\u00a0males and 766 females), aged between 18 and 69\u00a0years were included in the study. The mean\u00a0\u00b1\u00a0SD age of the participants was 39.78\u00a0\u00b1\u00a011.79\u00a0years. The age\u2010related effects for AT were found in men. In females, increasing age was associated with a rise in AT, PC, and PS plasma levels. No sex difference was found in AT plasma level. OCP\u2010taking is associated with a decrease in AT and an increase in PC plasma levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the largest study ever conducted on healthy individuals in the Iranian population, using specific reference interval results in accurate diagnosis of true AT, PC, and PS deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.13804","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T06:04:36Z","timestamp":1643868276000},"page":"626-634","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Reference interval of antithrombin, protein C, and protein S activities in healthy adults in Iran, the effect of age, sex, oral contraceptive intake, and menopause"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9875-8391","authenticated-orcid":false,"given":"Shadi","family":"Tabibian","sequence":"first","affiliation":[{"name":"Department of Hematology and Blood Banking Faculty of Allied Medicine Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majid","family":"Khoshmirsafa","sequence":"additional","affiliation":[{"name":"Immunology Research Center Institute of Immunology and Infectious Diseases Iran University of Medical Sciences Tehran Iran"},{"name":"Department of Immunology School of Medicine Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa","family":"Paridar","sequence":"additional","affiliation":[{"name":"Deputy of Management and Resources Development Ministry of Health and Medical Education Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbas","family":"Motevalian","sequence":"additional","affiliation":[{"name":"Department of Epidemiology School of Public Health Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahdi","family":"Shekarabi","sequence":"additional","affiliation":[{"name":"Immunology Research Center Institute of Immunology and Infectious Diseases Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0070-6620","authenticated-orcid":false,"given":"Majid","family":"Safa","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking Faculty of Allied Medicine Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.08022.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002781"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14667"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12456"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12219"},{"key":"e_1_2_8_7_1","volume-title":"Clinical and Laboratory Standards Institute: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline","author":"Horowitz G","year":"2008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2307\/3001634"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/36.2.265"},{"key":"e_1_2_8_10_1","unstructured":"Clinical and Laboratory Standards Institute.Defining establishing and verifying reference intervals in the clinical laboratory; approved guideline. CLSI document C28\u2010A3C 28. Wayne PA: Clinical and Laboratory Standards Institute; 2008 61."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14648"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1990.tb02541.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2013.07.003"},{"key":"e_1_2_8_14_1","first-page":"345","article-title":"Antithrombin levels in healthy Pakistani males","volume":"25","author":"Rahman M","year":"2009","journal-title":"Pak J Med Sci"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1994.tb04832.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1532\/LH96.05029"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.037515"},{"issue":"02","key":"e_1_2_8_18_1","first-page":"226","article-title":"The VITA project: population\u2010based distributions of protein C, antithrombin III, heparin\u2010cofactor II and plasminogen\u2010relationship with physiological variables and establishment of reference ranges","volume":"75","author":"Rodeghiero F","year":"1996","journal-title":"Thromb Haemost"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649566"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.1222936.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1532\/IJH97.A20514"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02813.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21992"}],"container-title":["International Journal of Laboratory Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijlh.13804","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ijlh.13804","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijlh.13804","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T19:34:22Z","timestamp":1692819262000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ijlh.13804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,2]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1111\/ijlh.13804"],"URL":"https:\/\/doi.org\/10.1111\/ijlh.13804","archive":["Portico"],"relation":{},"ISSN":["1751-5521","1751-553X"],"issn-type":[{"value":"1751-5521","type":"print"},{"value":"1751-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,2]]},"assertion":[{"value":"2021-08-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}