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76 Venous thrombosis under oral contraceptives: impact of risk factors
S118
2nd Int. Symp. on Women’s Health Issues in Thrombosis and Haemostasis / Thrombosis Research 119 Suppl. 1 (2007) S97–S118
described that mild hemostatic defects could be a cause of menorrhagia in substantial number of cases. Objective: To estimate prevalence of coagulation disorders in females with diagnosed menorrhagia. Methods: Thirty-eight women (36.1±8.6 years) with symptoms of menorrhagia have been studied. Menorrhagia have been verified using semiquantitive method Pictorial Bleeding Assessment Chart (PBAC) with score >100 (equivalent >80 ml blood). Bleeding time (BT), PT, aPTT, VWF:Ag and VWF:Ac, as well as FII, FV, FVII, FVIII, FIX, FX and F XI activity, fibrinogen and D-dimer have been analyzed. Results: Twenty eight women (74%) have had objectively verified menorrhagia (PBAC > 100). Coagulation defects have been found in 9 women (32%): decreased FIX:Ac in 3 (11%), decreased FII:Ac in 2 (7%), while 2 women matched criteria for mild VWD type 1; 1 woman (4%) is a hemophilia C carrier while one had prolonged PT. Women with coagulation disorders have had longer duration of menstrual bleeding (8.8±1.8 vs 8.3±3.5 days; p = 0,028), and lower levels of hemoglobin (106.5±11.2 vs 119.9±17.1 g/L; p = 0.044) and serum iron (6.4±4.3 vs 11.6±6.7 mmol/L; p < 0.05) in comparison to those without such disorders. Those women have prolonged aPTT (33.0±8.6s vs 27.0±2.6s, p = 0.002), lower level of fibrinogen (2.5±0.6 vs 2.9±0.6 g/L, p = 0.079) and higher level of D-dimer (258.1±154.0 vs 165.8±77.9 ng/mL; p = 0.008), while BT and PT showed no difference. Interpretation: About 3/4 patients with symptoms of menorrhagia really have an excessive blood loss during period verified with PBAC score. The prevalence of coagulation disorders in this group is high since one third of women with verified menorrhagia have some type of coagulation defect, while those disorders are associated with longer period duration and significant anemia. It seems that upregulated fibrinolysis also contributes to the bleeding tendency in those women. Conclusions: We have observed high incidence of coagulation disorders in women with verified menorrhagia. However including more patients and completing the study is mandatory before any definitive conclusion and possible inclusion of routine coagulation screening in diagnosis algorithm for women with menorrhagia.
76 Venous thrombosis under oral contraceptives: impact of risk factors J. Conard1 *, G. Plu-Bureau1,2 , K. Adida1 , M.H. Horellou1 . and Thrombosis Unit, 2 Gynecology Unit, Hˆ otel-Dieu Hospital, Paris, France 1 Hemostasis
Objectives: The aim of this study was to determine the characteristics of risk factors in patients with venous thromboembolism (VTE) associated with different oral contraceptives (OC). Methods: One hundred and ninety-eight patients were consecutively recruited at the outpatient clinic. The type of VTE, name of OC and characteristics of the patient were recorded and a thrombophilia screening performed. Results: Women were classified into three groups: low-dose (15 20 mg) [n = 99] or moderate-dose (30 mg) [n = 44] ethinyl estradiol (EE) associated with a 3rd generation progestin, or a higher dose (35 mg) with cyproterone acetate [n = 55]. The mean age at the time of VTE was 31.3±9.4 (SD) and 48 women were over 40 (24%). Obesity was present in 6%. In 60 women, VTE occurred during the first year of use. No triggering factor was found in 75. The most common risk factors were long trip, surgery or plaster cast. A thrombophilia was detected in 98 women and a family history of VTE reported by 109 women. Women with VTE during OC containing cyproterone acetate were significantly younger and had less associated risk factors than women of the two other groups. Conclusion: Risk factors associated with OC use were present in more than 50% of women and a number of VTE could have been prevented. This underlines the importance of careful interview before OC use.
77 Oral or vaginal administration of ethinyl estradiol has a similar impact on liver proteins and coagulation markers: results of a randomized, cross-over study R. Sitruk-Ware1 , G. Plu-Bureau2 , J. Menard3 , J. Conard4 *, S. Kumar1 , J.C. Thalabard2 , B. Tokay1 , P. Bouchard5 . 1 Population Council, New York, USA, 2 Endocrinology Gynecology Unit, Hˆ otel-Dieu, Paris; 3 University Paris 5; 4 Hemostasis Thrombosis Unit, Hˆ otel-Dieu, Paris; 5 Department of Endocrinology, Saint Antoine Hospital, Paris, France The use of oral contraceptives (OCs) is associated with an increased risk of venous thromboembolism (VTE). The risk is influenced by many factors including dose of ethinyl estradiol (EE) and type of progestin. Changes in hemostasis and SHBG (sex hormone binding globulin), a marker of estrogenicity (and potentially of VTE), have been observed. Objectives: The study was designed to compare the effects of the route of administration of the same dose of EE, given alone, on liver proteins and hemostasis. Methods: The study is a randomized, single-center, cross-over study of 14 healthy, postmenopausal women. They received either 15 mg of EE orally or a vaginal ring releasing 15 mg of EE for 21 days, with a 4 6 week wash-out period. Hemostasis, lipids, angiotensinogen and SHBG concentration were measured. Results: Concentrations of SHBG, angiotensinogen, D-dimers and plasminogen increased significantly during oral and vaginal administration of EE, and in a similar fashion. Antithrombin, protein S and activated protein C resistance were also significantly modified during both routes of administration (p < 0.02). Conclusion: Vaginal or oral administration of EE alone produced changes similar in direction and magnitude. These findings contrast with those obtained after oral or non-oral administration of estradiol (E2) for menopausal treatment, where non-oral administration produced no change. The assumption that the nonoral administration of estrogen will avoid the first-pass effect on the liver appears to be true for E2 , but not for EE. Thus, the contraindications to OC containing EE also apply to non-oral contraceptives containing EE.
2nd Int. Symp. on Women’s Health Issues in Thrombosis and Haemostasis / Thrombosis Research 119 Suppl. 1 (2007) S97–S118
described that mild hemostatic defects could be a cause of menorrhagia in substantial number of cases. Objective: To estimate prevalence of coagulation disorders in females with diagnosed menorrhagia. Methods: Thirty-eight women (36.1±8.6 years) with symptoms of menorrhagia have been studied. Menorrhagia have been verified using semiquantitive method Pictorial Bleeding Assessment Chart (PBAC) with score >100 (equivalent >80 ml blood). Bleeding time (BT), PT, aPTT, VWF:Ag and VWF:Ac, as well as FII, FV, FVII, FVIII, FIX, FX and F XI activity, fibrinogen and D-dimer have been analyzed. Results: Twenty eight women (74%) have had objectively verified menorrhagia (PBAC > 100). Coagulation defects have been found in 9 women (32%): decreased FIX:Ac in 3 (11%), decreased FII:Ac in 2 (7%), while 2 women matched criteria for mild VWD type 1; 1 woman (4%) is a hemophilia C carrier while one had prolonged PT. Women with coagulation disorders have had longer duration of menstrual bleeding (8.8±1.8 vs 8.3±3.5 days; p = 0,028), and lower levels of hemoglobin (106.5±11.2 vs 119.9±17.1 g/L; p = 0.044) and serum iron (6.4±4.3 vs 11.6±6.7 mmol/L; p < 0.05) in comparison to those without such disorders. Those women have prolonged aPTT (33.0±8.6s vs 27.0±2.6s, p = 0.002), lower level of fibrinogen (2.5±0.6 vs 2.9±0.6 g/L, p = 0.079) and higher level of D-dimer (258.1±154.0 vs 165.8±77.9 ng/mL; p = 0.008), while BT and PT showed no difference. Interpretation: About 3/4 patients with symptoms of menorrhagia really have an excessive blood loss during period verified with PBAC score. The prevalence of coagulation disorders in this group is high since one third of women with verified menorrhagia have some type of coagulation defect, while those disorders are associated with longer period duration and significant anemia. It seems that upregulated fibrinolysis also contributes to the bleeding tendency in those women. Conclusions: We have observed high incidence of coagulation disorders in women with verified menorrhagia. However including more patients and completing the study is mandatory before any definitive conclusion and possible inclusion of routine coagulation screening in diagnosis algorithm for women with menorrhagia.
76 Venous thrombosis under oral contraceptives: impact of risk factors J. Conard1 *, G. Plu-Bureau1,2 , K. Adida1 , M.H. Horellou1 . and Thrombosis Unit, 2 Gynecology Unit, Hˆ otel-Dieu Hospital, Paris, France 1 Hemostasis
Objectives: The aim of this study was to determine the characteristics of risk factors in patients with venous thromboembolism (VTE) associated with different oral contraceptives (OC). Methods: One hundred and ninety-eight patients were consecutively recruited at the outpatient clinic. The type of VTE, name of OC and characteristics of the patient were recorded and a thrombophilia screening performed. Results: Women were classified into three groups: low-dose (15 20 mg) [n = 99] or moderate-dose (30 mg) [n = 44] ethinyl estradiol (EE) associated with a 3rd generation progestin, or a higher dose (35 mg) with cyproterone acetate [n = 55]. The mean age at the time of VTE was 31.3±9.4 (SD) and 48 women were over 40 (24%). Obesity was present in 6%. In 60 women, VTE occurred during the first year of use. No triggering factor was found in 75. The most common risk factors were long trip, surgery or plaster cast. A thrombophilia was detected in 98 women and a family history of VTE reported by 109 women. Women with VTE during OC containing cyproterone acetate were significantly younger and had less associated risk factors than women of the two other groups. Conclusion: Risk factors associated with OC use were present in more than 50% of women and a number of VTE could have been prevented. This underlines the importance of careful interview before OC use.
77 Oral or vaginal administration of ethinyl estradiol has a similar impact on liver proteins and coagulation markers: results of a randomized, cross-over study R. Sitruk-Ware1 , G. Plu-Bureau2 , J. Menard3 , J. Conard4 *, S. Kumar1 , J.C. Thalabard2 , B. Tokay1 , P. Bouchard5 . 1 Population Council, New York, USA, 2 Endocrinology Gynecology Unit, Hˆ otel-Dieu, Paris; 3 University Paris 5; 4 Hemostasis Thrombosis Unit, Hˆ otel-Dieu, Paris; 5 Department of Endocrinology, Saint Antoine Hospital, Paris, France The use of oral contraceptives (OCs) is associated with an increased risk of venous thromboembolism (VTE). The risk is influenced by many factors including dose of ethinyl estradiol (EE) and type of progestin. Changes in hemostasis and SHBG (sex hormone binding globulin), a marker of estrogenicity (and potentially of VTE), have been observed. Objectives: The study was designed to compare the effects of the route of administration of the same dose of EE, given alone, on liver proteins and hemostasis. Methods: The study is a randomized, single-center, cross-over study of 14 healthy, postmenopausal women. They received either 15 mg of EE orally or a vaginal ring releasing 15 mg of EE for 21 days, with a 4 6 week wash-out period. Hemostasis, lipids, angiotensinogen and SHBG concentration were measured. Results: Concentrations of SHBG, angiotensinogen, D-dimers and plasminogen increased significantly during oral and vaginal administration of EE, and in a similar fashion. Antithrombin, protein S and activated protein C resistance were also significantly modified during both routes of administration (p < 0.02). Conclusion: Vaginal or oral administration of EE alone produced changes similar in direction and magnitude. These findings contrast with those obtained after oral or non-oral administration of estradiol (E2) for menopausal treatment, where non-oral administration produced no change. The assumption that the nonoral administration of estrogen will avoid the first-pass effect on the liver appears to be true for E2 , but not for EE. Thus, the contraindications to OC containing EE also apply to non-oral contraceptives containing EE.