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      A case-control study on factor V Leiden: an independent, gender-dependent risk factor for venous thromboembolism

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          Abstract

          Background

          Activated protein C resistance (APCR) due to factor V Leiden (FVL) mutation (R506Q) is a major risk factor in patients with venous thromboembolism (VTE). The present study investigated the clinical manifestations and the risk of venous thromboembolism regarding multiple clinical, laboratory, and demographic properties in FVL patients.

          Material and methods

          A retrospective cross-sectional analysis was conducted on a total of 288 FVL patients with VTE according to APCR. In addition, 288 VET control samples, without FVL mutation, were also randomly selected. Demographic information, clinical manifestations, family and treatment history were recorded, and specific tests including t-test, chi-square and uni- and multi-variable regression tests applied.

          Results

          APCR was found to be 2.3 times significantly more likely in men (OR: 2.1, p < 0.05) than women. The risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in APCR patients was 4.5 and 3.2 times more than the control group, respectively ( p < 0.05). However, APCR could not be an independent risk factor for arterial thrombosis (AT) and pregnancy complications. Moreover, patients were evaluated for thrombophilia panel tests and showed significantly lower protein C and S than the control group and patients without DVT ( p < 0.0001).

          Conclusion

          FVL mutation and APCR abnormality are noticeable risk factors for VTE. Screening strategies for FVL mutation in patients undergoing surgery, oral contraceptive medication, and pregnancy cannot be recommended, but a phenotypic test for activated protein C resistance should be endorsed in patients with VTE.

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          Most cited references31

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          2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.

          Stavros V Konstantinides, Adam Torbicki, Giancarlo Agnelli … (2014)
          Article 0 comments Cited 705 times – based on 0 reviews     Review now
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            Consanguineous marriages : Preconception consultation in primary health care settings.

            Hanan Hamamy (2012)
            Consanguinity is a deeply rooted social trend among one-fifth of the world population mostly residing in the Middle East, West Asia and North Africa, as well as among emigrants from these communities now residing in North America, Europe and Australia. The mounting public awareness on prevention of congenital and genetic disorders in offspring is driving an increasing number of couples contemplating marriage and reproduction in highly consanguineous communities to seek counseling on consanguinity. Primary health care providers are faced with consanguineous couples demanding answers to their questions on the anticipated health risks to their offspring. Preconception and premarital counseling on consanguinity should be part of the training of health care providers particularly in highly consanguineous populations.
            Article 0 comments Cited 67 times – based on 0 reviews     Review now
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              Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men.

              M Stampfer, R Eisenberg, C Hennekens … (1995)
              A specific point mutation in the gene coding for coagulation factor V is associated with resistance to degradation by activated protein C, a recently described abnormality of coagulation that may be associated with an increased risk of venous thrombosis. Whether this mutation also predisposes patients to arterial thrombosis is unknown, as is the value of screening for the mutation in order to define the risk of venous thrombosis among unselected healthy people. Among 14,916 apparently healthy men in the Physicians' Health Study who provided base-line blood samples, 374 had myocardial infarctions, 209 had strokes, and 121 had deep venous thrombosis, pulmonary embolism, or both, during a mean follow-up of 8.6 years. We determined whether a mutation at nucleotide position 1691 of the factor V gene was present or absent in these 704 men and in an equal number of matched participants who remained free of vascular disease. The prevalence of heterozygosity for the mutation among men who had myocardial infarctions (6.1 percent, P = 0.9) or strokes (4.3 percent, P = 0.4) was similar to that among men who remained free of vascular disease (6.0 percent). However, the prevalence of the mutation was significantly higher among men who had venous thrombosis, pulmonary embolism, or both (11.6 percent, P = 0.02). In adjusted analyses, the relative risk of venous thrombosis among men with the mutation was 2.7 (95 percent confidence interval, 1.3 to 5.6; P = 0.008). This increased risk was seen with primary venous thrombosis (relative risk, 3.5; 95 percent confidence interval, 1.5 to 8.4; P = 0.004) but not with secondary venous thrombosis (relative risk, 1.7; 95 percent confidence interval, 0.6 to 5.3; P = 0.3), and it was most apparent among older men. Specifically, the prevalence of the mutation among men over the age of 60 in whom primary venous thrombosis developed was 25.8 percent (relative risk, 7.0; 95 percent confidence interval, 2.6 to 19.1; P < 0.001). In a large cohort of apparently healthy men, the presence of a specific point mutation in the factor V gene was associated with an increased risk of venous thrombosis, particularly primary venous thrombosis. The presence of the mutation was not associated with an increased risk of myocardial infarction or stroke. This mutation appears to be the most common inherited factor thus far recognized that predisposes patients to venous thrombosis.
              Article 0 comments Cited 59 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Abbas Khosravi:
                ORCID: http://orcid.org/0000-0001-5213-106X
                a-khosravi@razi.tums.ac.ir
                Journal
                Journal ID (nlm-ta): Thromb J
                Journal ID (iso-abbrev): Thromb J
                Title: Thrombosis Journal
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-9560
                Publication date (Electronic): 19 October 2021
                Publication date PMC-release: 19 October 2021
                Publication date Collection: 2021
                Volume: 19
                Electronic Location Identifier: 74
                Affiliations
                [1 ]Transfusion Research center, High Institute for Research and Education in Transfusion, Tehran, Iran
                [2 ]GRID grid.411324.1, ISNI 0000 0001 2324 3572, PRASE and Biology Department, , Faculty of Sciences, Lebanese University, ; Beirut, Lebanon
                [3 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of hematology, School of Allied Medical Sciences, , Tehran University of Medical Sciences, ; Tehran, Iran
                [4 ]GRID grid.411230.5, ISNI 0000 0000 9296 6873, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, ; Ahvaz, Iran
                [5 ]GRID grid.411746.1, ISNI 0000 0004 4911 7066, Department of Hematology and Blood Banking, , Faculty of Allied Medicine, Iran University of Medical Sciences, ; Tehran, Iran
                [6 ]GRID grid.412266.5, ISNI 0000 0001 1781 3962, Hematology Department, , Tarbiat Modares University, ; Tehran, Iran
                [7 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, School of Public Health, , Tehran University of Medical Sciences, ; Tehran, Iran
                [8 ]GRID grid.411463.5, ISNI 0000 0001 0706 2472, Islamic Azad University, ; North-Tehran Branch, Tehran, Iran
                [9 ]GRID grid.411230.5, ISNI 0000 0000 9296 6873, Department of Anesthesiology, , Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, ; Ahvaz, Iran
                Author information
                http://orcid.org/0000-0001-5213-106X
                Article
                Publisher ID: 328
                DOI: 10.1186/s12959-021-00328-0
                PMC ID: 8527672
                PubMed ID: 34666770
                SO-VID: 6124087b-a195-44ec-80a7-613b88ef8eb7
                Copyright © © The Author(s) 2021
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 16 February 2021
                Date accepted : 10 October 2021
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: apcr,factor v leiden,thrombophilia,venous thromboembolism,dvt,pe,arterial thrombosis
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: apcr, factor v leiden, thrombophilia, venous thromboembolism, dvt, pe, arterial thrombosis

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