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

Abstract

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

Thrombophilia Testing in Patients with Venous Thrombosis

“…17 One patient in the calf thrombosis group was heterozygous for factor V Leiden, which would not change the approach to treatment for the calf vein thrombosis but may have other implications for blood relatives, especially those who are contemplating birth control pills or hormone replacement therapy. 18 The value of knowing about positive markers such as factor V Leiden, prothrombin 20210A and MTHFR in this group is less evident. However, some of these patients were of child-bearing age and developed SVT during or after a previous pregnancy.…”

Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening

“…In fact, it is important to remember that age is an independent cardiovascular risk factor that favors thrombotic events. On the other hand, selective thrombophilia screening in women with a personal and/or family history of VTE could itself be considered a contraindication for OC, regardless of any thrombophilic defect (82). Selective screening based on prior personal or family history has been recommended (80,81).…”