Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives

Harris, Geoffrey M.; Stendt, Caroline L.; Vollenhoven, Beverley; Gan, Tian; Tipping, Peter G.

doi:10.1002/(sici)1096-8652(199903)60:3<175::aid-ajh1>3.0.co;2-x

Cited by 86 publications

(43 citation statements)

References 29 publications

(29 reference statements)

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“…TFPI is cleared from the circulation by the liver and kidneys [32]. The decrease in free TFPI induced by oral contraceptives might be caused by changes in synthesis, clearance or lipoprotein profile [30,34].…”

Section: Discussionmentioning

confidence: 95%

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Different effects of oral contraceptives containing different progestogens on protein S and tissue factor pathway inhibitor

Vliet¹,

Bertina

Dahm

et al. 2008

J Thromb Haemost

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To cite this article: van Vliet HAAM, Bertina RM, Dahm AEA, Rosendaal FR, Rosing J, Morten Sandset P, Helmerhorst FM. Different effects of oral contraceptives containing different progestogens on protein S and tissue factor pathway inhibitor. J Thromb Haemost 2008; 6: 346-51.Summary. Background: Oral contraceptives (OC) containing different types of progestogens induce different sensitivities to activated protein C (APC) measured with the thrombin generation-based APC-resistance test. These differences in APC resistance may be the biological explanation for the differences in thrombotic risk of the various pills. The mechanistic basis of APC resistance observed in OC users is unknown. Our objective was to study the effect of OC on the two main determinants of the APC-resistance test, free protein S and free tissue factor pathway inhibitor (TFPI). Patients/ methods: We measured free protein S and free TFPI in 156 users of various types of OC. Results: Users of desogestrel-containing OC, known to double the risk of thrombosis compared with levonorgestrel-containing OC, had lower free protein S (24 vs. 33 U dL ) and TFPI free antigen (2.9 vs. 3.6 ng mL )1 ) levels than users of OC containing levonorgestrel. Women using cyproterone acetate-containing OC, known to confer a high thrombotic risk, had the lowest free protein S (19 U dL )1) and free TPFI antigen (2.5 ng mL ) and TFPI antigen levels (3.2 ng mL )1 ) than users of levonorgestrelcontaining OC. Low free protein S and low free TFPI antigen levels were associated with an increased resistance to APC, an established risk factor for thrombosis. Conclusions: This study observed that the differences in APC resistance induced by OC containing different progestogens can at least in part be explained by different effects of OC on free protein S and TFPI.

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Section: Discussionmentioning

confidence: 95%

“…Concerning TFPI, other studies observed that oral contraceptives lower TFPI activity, and free and total antigen [9,30].…”

Section: Discussionmentioning

confidence: 99%

Different effects of oral contraceptives containing different progestogens on protein S and tissue factor pathway inhibitor

Vliet¹,

Bertina

Dahm

et al. 2008

J Thromb Haemost

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“…There are anecdotal reports of the disappearance of bleeding symptoms during treatment, with normalization of vWF and FVIII levels in several cases [48]. A significant increase in FVIII and vWF levels in normal women on oral contraception has been shown in some but not all studies [31,[49][50][51]. However, the hemostatic effects are variable with markedly elevated clotting factor levels in some individuals [50].…”

Section: Oral Contraceptivesmentioning

confidence: 99%

von Willebrand's disease and menorrhagia: Prevalence, diagnosis, and management

Kujovich¹

2005

American J Hematol

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The reported prevalence of von Willebrand's disease (vWD) is increased in women with menorrhagia, with current estimates ranging from 5% to 20%. The consistent results of multiple studies suggest testing should be included in the evaluation of patients with menorrhagia, especially in unexplained cases and prior to surgical intervention. Although a cyclic variation in von Willebrand's factor levels has not been confirmed, several studies suggest lower levels during menses and the early follicular phase. Menorrhagia is one of the most common bleeding manifestations of von Willebrand's disease, reported by 60-95% of women afflicted with this bleeding disorder. Menorrhagia is typically severe, often resulting in anemia and interfering with quality of life. Despite the frequency of menorrhagia, there is no consensus on optimal management. Although oral contraceptives are frequently prescribed, there are no studies confirming their efficacy using objective measures of response. Desmopressin was associated with an 80-92% response rate in several uncontrolled studies relying on patient assessment of efficacy. However, a small, randomized trial found no significant reduction in menstrual blood flow compared with placebo. There are anecdotal reports of the successful use of antifibrinolytic agents alone and in combination with other therapies. There are no studies comparing the relative efficacy and safety of the available medical therapies for von Willebrand's disease associated menorrhagia. Until these studies are completed, treatment should be individualized based on von Willebrand's disease subtype, patient age, contraceptive needs, and personal preference. Am.

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“…TFPI binds directly and inhibits the earliest steps in extrinsic pathway activation by binding factor Xa (which involved in the activation of prothrombin to thrombin) and tissue factor (TF)/factor VIIa complexes in an inactive quaternary complex (30). Low plasma TFPI levels have been reported in patients with ischemic stroke (31), thrombotic thrombocytopenic purpura (32), and in women taking combined oral contraceptives (33).…”

Section: Introductionmentioning

confidence: 98%

Increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels in patients with primary hyperparathyroidism

Erem

Koçak²,

Nuhoğlu³

et al. 2009

European Journal of Endocrinology

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Background and objectives: Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality and morbidity. Little is known about hemostatic features of patients with PHPT. To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels in these patints have not been investigated. Therefore, the main purpose of this study was to evaluate the markers of endogenous coagulation/fibrinolysis, including TFPI and TAFI, and to investigate the relationships between serum calcium and PTH and these hemostatic parameters in patients with PHPT. Design and methods: Twenty-four patients with PHPT and 20 age-, sex-, and-weight-matched healthy controls were included in the study. Tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor-1 (PAI-1), TFPI, and TAFI were measured. The relationships between serum calcium, phosphorus, and PTH and these hemostatic parameters were examinated. Results: Compared with the control subjects, t-PA, PAI-1, and PAI-1/t-PA ratios were significantly increased in patients with PHPT (P!0.0001), whereas TFPI levels were significantly decreased (P!0.0001). Plasma TAFI Ag levels did not significantly change in patients with PHPT compared with the controls. In patients with PHPT, serum phosphorus was negatively correlated with plasma PAI-1 Ag levels and PAI-1/t-PA ratio (r: K0.453, P!0.05; r: K0.580, P!0.01 respectively). There was a positive correlation between Cl/P ratio and plasma PAI-1 levels and PAI-1/t-PA ratio (r: 0.434, P!0.05; r: 0.528, P!0.05 respectively). iPTH was positively correlated with plasma PAI-1/t-PA ratio (r: 0.429, P!0.05). Interpretation and conclusions: In conclusion, we found some important differences in the hemostatic parameters between the patients with PHPT and healthy controls. Increased PAI-1, PAI-1/t-PA ratios and decreased TFPI levels in these patients represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess mortality due to cardiovascular disease seen in patients with PHPT.

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Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives

Cited by 86 publications

References 29 publications

Different effects of oral contraceptives containing different progestogens on protein S and tissue factor pathway inhibitor

Different effects of oral contraceptives containing different progestogens on protein S and tissue factor pathway inhibitor

von Willebrand's disease and menorrhagia: Prevalence, diagnosis, and management

Increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels in patients with primary hyperparathyroidism

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