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

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

doi:10.1002/(sici)1096-8652(199903)60:3<175::aid-ajh1>3.3.co;2-o

Cited by 26 publications

(31 citation statements)

References 13 publications

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“…Consistent with previous reports, we found that TFPI antigen was positively correlated with the concentration of LDL-C [23]. Moreover, the possibility that sex steroids can influence TFPI by a mechanism other than via lipids was suggested in the study of Harris et al [19], where lower levels of TFPI in patients taking the oral contraceptive pill were not associated with a lower LDL-C level. However, given that there was a 26 % decrease in TFPI, the change in lipoprotein levels with HRT at most only accounts for a small proportion of the reduction in TFPI activity.…”

Section: Discussionsupporting

confidence: 91%

“…This reduction is of a similar degree to the 25 % decrease in the level of TFPI antigen reported previously in women on the oral contraceptive pill [19]. HRT use was associated with decreases in VIIa and VIIc, suggesting a decreased tendency for extrinsic pathway activation, and also with a reduction in TFPI antigen concentration, indicating a reduced potential to inhibit extrinsic pathway activation.…”

Section: Discussionsupporting

confidence: 83%

“…Although the mechanisms underlying this increase in thrombin generation are yet to be defined, several lines of evidence point to a role for the extrinsic coagulation pathway. Furthermore, there is evidence for an effect of sex steroids on tissue factor pathway inhibitor (TFPI), the main physiological inhibitor of the tissue factor-VIIa complex [18], with TFPI levels being reduced in patients on the oral contraceptive pill [19]. Furthermore, there is evidence for an effect of sex steroids on tissue factor pathway inhibitor (TFPI), the main physiological inhibitor of the tissue factor-VIIa complex [18], with TFPI levels being reduced in patients on the oral contraceptive pill [19].…”

Section: Introductionmentioning

confidence: 99%

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Effects of combined oral hormone replacement therapy on tissue factor pathway inhibitor and factor VII

Peverill¹,

Teede²,

Smolich³

et al. 2001

Clinical Science

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Oral combined hormone replacement therapy (HRT) with oestradiol and norethisterone increases plasma levels of prothrombin fragment 1+2 (F1+2), indicating an increase in thrombin generation, but the mechanisms underlying this increase are uncertain. The aim of this randomized, placebo-controlled study was to determine whether an increase in factor VII, a factor that combines with tissue factor to activate the extrinsic pathway, or a decrease in tissue factor pathway inhibitor (TFPI), an inhibitor of extrinsic pathway activation, may contribute to increases in thrombin generation occurring with HRT. Healthy postmenopausal women aged 50-75 years received placebo (n=19) or oral combined HRT (n=18) and had blood collected for measurement of factor VII coagulation activity (VIIc), activated factor VII (VIIa) and TFPI at baseline and at 6 weeks. Baseline characteristics were similar in the two groups, including age, body mass index and cholesterol levels. As reported previously, HRT increased the F1+2 concentration by 20%. Placebo had no effect on VIIc, VIIa or TFPI, but 6 weeks of combined HRT decreased VIIc [from 1.11+/-0.06 (mean+/-S.E.M.) to 1.03+/-0.06 i.u./ml; P<0.03], VIIa [from 43.9; 10.8-198.3 (median; range) to 35.0; 6.3-66.8 m-units/ml; P<0.03] and TFPI [from 81.3+/-6.5 to 60.4+/-5.5 ng/ml; P<0.0001]. The decrease in TPFI with HRT was not correlated with the elevation in F1+2 levels. In conclusion, the increase in thrombin generation seen with HRT is not due to an effect on factor VII; in addition, while a contribution from the decrease in TFPI is possible, increased thrombin generation is not directly related to the decrease in TFPI.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Effects of combined oral hormone replacement therapy on tissue factor pathway inhibitor and factor VII

Peverill¹,

Teede²,

Smolich³

et al. 2001

Clinical Science

Self Cite

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“…The use of exogenous female hormones is a well‐recognized risk factor for venous thrombosis. This was also associated with a significant reduction in TFPI levels 107, 121. A study reported up to 12% (TFPI activity) and 30% (TFPI antigen) decrease which, interestingly, was independent of blood lipids 122.…”

Section: The Clinical Value Of Tfpimentioning

confidence: 89%

Tissue factor pathway inhibitor: structure, biology and involvement in disease

Lwaleed

Bass

2005

The Journal of Pathology

174

120

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Tissue factor (TF)-initiated coagulation plays a significant role in the pathophysiology of many diseases, including cancer and inflammation. Tissue factor pathway inhibitor (TFPI) is a plasma Kunitz-type serine protease inhibitor, which modulates initiations of coagulation induced by TF. In a factor (F) Xa-dependent feedback system, TFPI binds directly and inhibits the TF-FVII/FVIIa complex. Normally, TFPI exists in plasma both as a full-length molecule and as variably carboxy-terminal truncated forms. TFPI also circulates in complex with plasma lipoproteins. The levels and the dual inhibitor effect of TFPI on FXa and TF-FVII/FVIIa complex offers insight into the mechanisms of various pathological conditions triggered by TF. The use of selective pharmacological inhibitors has become an indispensable tool in experimental haemostasis and thrombosis research. In vivo administration of recombinant TFPI (rTFPI) in an experimental animal model prevents thrombosis (and re-thrombosis after thrombolysis), reduces mortality from E. coli-induced-septic shock, prevents fibrin deposition on subendothelial human matrix and protects against disseminated intravascular coagulation (DIC). Thus, TFPI may play an important role in modulating TF-induced thrombogenesis and it may also provide a unique therapeutic approach for prophylaxis and/or treatment of various diseases. In this review, we consider structural and biochemical aspects of the TFPI molecule and detail its inhibitory mechanisms and therapeutic implications in various disease conditions.

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“…Yet, it is clear that changes of several important blood coagulation parameters (such as prothrombin, protein S, FVIII, and tissue factor pathway inhibitor) are involved. [102][103][104][105] …”

Section: Resistance To Apc In the Absence Of Fv Leidenmentioning

confidence: 99%

Congenital and Acquired Activated Protein C Resistance

Nicolaes¹,

Dahlbäck²

2003

Seminars in Vascular Medicine

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Resistance to the anticoagulant action of activated protein C, APC resistance, is a highly prevalent risk factor for venous thrombosis among individuals of Caucasian origin. In most cases, APC resistance is associated with a single missense mutation in the gene for coagulation factor V (FV (Leiden)), which predicts the replacement of Arg (506) with a Gln at one of the cleavage sites for APC in factor V. Factor V is a Janus-faced protein with dual functions, serving as an essential nonenzymatic cofactor in both pro- and anticoagulant pathways. Procoagulant factor Va, generated after proteolysis by thrombin or factor Xa, is a cofactor to factor Xa in the activation of prothrombin, whereas anticoagulant factor V, generated after proteolysis by APC, functions as a cofactor in the APC-mediated degradation of FVIIIa. The FV (Leiden) mutation affects the anticoagulant response to APC at two distinct levels of the coagulation pathway, as it impairs degradation of both activated factor V and activated factor VIII, the latter effect inasmuch as FVLeiden is a poor APC cofactor. Several other genetic traits, some of them quite common, are known to affect the anticoagulant response to APC, but none of them cause the same severe APC-resistance phenotype as FV (Leiden) and their importance as risk factors for thrombosis is unclear. A poor APC response may also result from acquired conditions, some of which are clearly involved in the pathogenesis of venous thrombosis. Venous thrombosis is a typical multifactorial disease, the pathogenesis of which involves multiple gene-gene and gene-environment interactions. In many patients with severe thrombophilia, APC resistance is found as a contributing risk factor.

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

Cited by 26 publications

References 13 publications

Effects of combined oral hormone replacement therapy on tissue factor pathway inhibitor and factor VII

Effects of combined oral hormone replacement therapy on tissue factor pathway inhibitor and factor VII

Tissue factor pathway inhibitor: structure, biology and involvement in disease

Congenital and Acquired Activated Protein C Resistance

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