Venous thromboembolism in young women. Role of thrombophilic mutations and oral contraceptive use

Legnani, Cristina; Palareti, Gualtiero; Guazzaloca, Giuliana; Cosmi, Benilde; Lunghi, Barbara; Bernardi, Francesco; Coccheri, S.

doi:10.1053/euhj.2001.3082

Cited by 62 publications

(71 citation statements)

References 25 publications

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“…195 A high prothrombin level Ͼ110-115% of normal is associated with a 2-fold increased risk for VTE in the absence of prothrombin 20210GϾA heterozygosity. 111,186 • Although abnormalities in other coagulation or fibrinolytic proteins including PAI-1, tissue factor pathway inhibitor, thrombin activatable fibrinolysis inhibitor, and Protein Z have been reported in patients with venous thrombosis, a causal association has not been established.…”

Section: Acquired Disordersmentioning

confidence: 99%

“…75 The supraadditive effect of a Factor V Leiden allele and oral contraceptives was confirmed in other studies and a metaanalysis with odds ratios ranging from 11 to 41 for the combination of both risk factors. [111][112][113]115 Heterozygous women who use oral contraceptives have a 30-fold higher risk for cerebral vein thrombosis than nonusers without the mutation. 46 The risk for VTE is increased more than 100-fold in women homozygous for Factor V Leiden who use oral contraceptives.…”

Section: Oral Contraceptivesmentioning

confidence: 99%

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Factor V Leiden thrombophilia

Kujovich

2011

Genetics in Medicine

320

291

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Section: Acquired Disordersmentioning

confidence: 99%

Section: Oral Contraceptivesmentioning

confidence: 99%

Factor V Leiden thrombophilia

Kujovich

2011

Genetics in Medicine

320

291

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“…Several studies have reported COC use [5][6][7][8][9][10][11][30][31][32][33] and pregnancypostpartum [33][34][35][36] as contributing factors to the risk of VTE in women with factor V Leiden and/or prothrombin-G20210A. However, adequate interpretation of risks is hampered as most studies only reported relative risks and these estimates differ considerably.…”

Section: Oral Contraceptives Pregnancy and Mildmentioning

confidence: 99%

“…4 These recommendations are mainly based on case-control studies reporting increased relative risks of VTE during COC use in women with hereditary thrombophilic defects. [5][6][7][8][9][10][11] However, to qualify all hereditary thrombophilic defects as similarly strong risk factors might be questioned. The absolute risk of VTE in factor V Leiden carriers is estimated being 0.15 per 100 person-years, 12 whereas in antithrombin-, protein C-, or protein S-deficient persons these estimates range from 0.7 to 1.7 per 100 person-years, indicating a considerably higher degree of risk.…”

Section: Introductionmentioning

confidence: 99%

Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception

Vlijmen

Veeger

Middeldorp

et al. 2011

Blood

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Current guidelines discourage combined oral contraceptive (COC) use in women with hereditary thrombophilic defects. However, qualifying all hereditary thrombophilic defects as similarly strong risk factors might be questioned. Recent studies indicate the risk of venous thromboembolism (VTE) of a factor V Leiden mutation as considerably lower than a deficiency of protein C, protein S, or antithrombin. In a retrospective family cohort, the VTE risk during COC use and pregnancy (including postpartum) was assessed in 798 female relatives with or without a heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin G20210A mutation. Overall, absolute VTE risk in women with no, single, or combined defects was 0. Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 2375. Disclosures The authors; the Associate Editor David P. Lillicrap; and the CME questions author Laurie Barclay, freelance writer and reviewer, Medscape, LLC, declare no competing financial interest. Learning objectivesUpon completion of this activity, participants will be able to:1. Describe findings from previous studies and current guidelines in regard to COC use in women with hereditary thrombophilic defects.2. Describe findings from a retrospective family cohort study of the risk for VTE during COC use and pregnancy and the postpartum period among 798 female relatives of symptomatic probands with heterozygous, double heterozygous, or homozygous factor V Leiden or prothombin G20210A mutation.3. Describe clinical implications of these findings from the retrospective family cohort study.

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“…The presence of the G20210A mutation of the prothrombin gene increases the risk of DVT by 16-50-fold and of cerebral vein thrombosis by 150-fold in OC users vs. non users [5,9,10]. The prevalence of G20210A prothrombin polymorphism is estimated between 2-4% in the general population (more prevalent in Southern Europe).…”

mentioning

confidence: 99%

Thrombophilia in young women candidate to the pill: reasons for and against screening

Cosmi

Coccheri

2002

Pathophysiol Haemos Thromb

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Screening for thrombophilia in women candidate to the pill is still a matter of debate. Oral contraceptives may trigger venous thromboembolic events in carriers of common inherited thrombophilic defects. General screening is not cost-effective from an epidemiological point of view if the objective is to prevent death due to venous thromboembolism during oral contraception (OC). However, clinicians deal with single patients and personal and/ or family history for venous thromboembolism have limited value for identifying those women at risk of VTE complications during OC. A pharmacogenetics approach in prescribing OC on the basis of each woman's genetic make-up could increase drug safety. A proper evaluation of the cost-effectiveness, the medical, psychosocial and legal consequences is needed before general screening with genetic testing for inherited thrombophilia can be recommended before OC.The relative risk of venous thromboembolism (VTE) is increased by about 4-fold in users of oral contraceptives (OC), however the increase in the absolute risk is modest (from 1 case per 10.000 women years in non-pill users to 3 cases per 10.000 women years in pill users) [1]. It is estimated that more than 100 million women worldwide use OC. Although most OC users are healthy with a low background incidence of major disease, the large number of women who use OC worldwide means that even modest elevations in risk have the potential to affect a large number of women. OC can trigger VTE in carriers of unrecognised thrombophilic defects such as the R506Q mutation of factor V gene (FV Leiden) and the G20120A polymorphism in the prothrombin gene [2,3,4]. The estimated prevalence of these two defects ranges from 3-10% and 1-6% respectively in healthy Europeans. OC increase the risk of thrombotic complications in FV Leiden heterozygotes and homozygotes by 30-40-fold and 100-fold, respectively. OC increase the risk of cerebral vein thrombosis by 150-fold during in the presence of the prothrombin mutation G20120A [5]. An interaction with a synergistic effect between OC and FV Leiden has been shown by Vandenbroucke et al.[1]. The increase in venous thromboembolism is about 4-fold in OC users who are non carriers, about 7-fold in carriers of FV Leiden who do not use the pill and 35-fold in pill users who are also carriers of FV Leiden [1].Pharmacogenetics is the study of the hereditary basis for differences in populations' response to drugs. Pharmacogenetics has the potential to allow physicians to choose drugs depending on the patient's genetic make-up with the aim Fax +41 61 306 12 34 E-Mail karger@karger.ch www.Karger.com

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Venous thromboembolism in young women. Role of thrombophilic mutations and oral contraceptive use

Abstract: Our data showed a strong interaction between oral contraceptive use and the presence of either R506Q or G20210A mutations. In non-oral contraceptive users the risk of venous thromboembolism was significantly increased in carriers of R506Q but not in those with the G20210A mutation.

Cited by 62 publications

References 25 publications

Factor V Leiden thrombophilia

Factor V Leiden thrombophilia

Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception

Thrombophilia in young women candidate to the pill: reasons for and against screening

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