scholarly journals Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

2002 ◽  
Vol 17 (12) ◽  
pp. 3235-3241 ◽  
Author(s):  
E.M. Bladbjerg
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Tissue Factor ◽  
Blood Coagulation ◽  
Tissue Factor Pathway Inhibitor ◽  
Hormone Replacement ◽  
Coagulation Factor ◽  
Factor Vii ◽  
Coagulation Factor Vii ◽  
Tissue Factor Pathway

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

2001 ◽  
Vol 101 (1) ◽  
pp. 93-99 ◽  
Author(s):  
Roger E. PEVERILL ◽  
Helena J. TEEDE ◽  
Joseph J. SMOLICH ◽  
Erica MALAN ◽  
Dimitra KOTSOPOULOS ◽  
...  
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Tissue Factor ◽  
Thrombin Generation ◽  
Tissue Factor Pathway Inhibitor ◽  
Hormone Replacement ◽  
Factor Vii ◽  
Controlled Study ◽  
Extrinsic Pathway ◽  
Tissue Factor Pathway

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.

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

2001 ◽  
Vol 101 (1) ◽  
pp. 93 ◽  
Author(s):  
Roger E. PEVERILL ◽  
Helena J. TEEDE ◽  
Joseph J. SMOLICH ◽  
Erica MALAN ◽  
Dimitra KOTSOPOULOS ◽  
...  
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Hormone Replacement ◽  
Factor Vii ◽  
Tissue Factor Pathway

scholarly journals Circulating Tissue Factor Procoagulant Activity and Thrombin Generation in Patients with Type 2 Diabetes: Effects of Insulin and Glucose

2007 ◽  
Vol 92 (11) ◽  
pp. 4352-4358 ◽  
Author(s):  
Guenther Boden ◽  
Vijender R. Vaidyula ◽  
Carol Homko ◽  
Peter Cheung ◽  
A. Koneti Rao
Keyword(s):  
Type 2 Diabetes ◽  
Tissue Factor ◽  
Blood Coagulation ◽  
Coagulation Factor ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Coagulation Factor Vii ◽  
Glucose Levels ◽  
Study Protocols

Abstract Context: Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation. Objective: Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM. Design: Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Setting: The study took place at a clinical research center. Study Participants: Participants included 18 T2DM patients and 22 nondiabetic controls. Results: Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (∼7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA. Conclusion: We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.

scholarly journals A candidate activation pathway for coagulation factor VII

2019 ◽  
Vol 476 (19) ◽  
pp. 2909-2926
Author(s):  
Tina M. Misenheimer ◽  
Kraig T. Kumfer ◽  
Barbara E. Bates ◽  
Emily R. Nettesheim ◽  
Bradford S. Schwartz
Keyword(s):  
Tissue Factor ◽  
Blood Coagulation ◽  
Factor Viia ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Factor Vii ◽  
Factor X ◽  
Contact Activation ◽  
Coagulation Factor Vii ◽  
Factor Viiia

Abstract The mechanism of generation of factor VIIa, considered the initiating protease in the tissue factor-initiated extrinsic limb of blood coagulation, is obscure. Decreased levels of plasma VIIa in individuals with congenital factor IX deficiency suggest that generation of VIIa is dependent on an activation product of factor IX. Factor VIIa activates IX to IXa by a two-step removal of the activation peptide with cleavages occurring after R191 and R226. Factor IXaα, however, is IX cleaved only after R226, and not after R191. We tested the hypothesis that IXaα activates VII with mutant IX that could be cleaved only at R226 and thus generate only IXaα upon activation. Factor IXaα demonstrated 1.6% the coagulant activity of IXa in a contact activation-based assay of the intrinsic activation limb and was less efficient than IXa at activating factor X in the presence of factor VIIIa. However, IXaα and IXa had indistinguishable amidolytic activity, and, strikingly, both catalyzed the cleavage required to convert VII to VIIa with indistinguishable kinetic parameters that were augmented by phospholipids, but not by factor VIIIa or tissue factor. We propose that IXa and IXaα participate in a pathway of reciprocal activation of VII and IX that does not require a protein cofactor. Since both VIIa and activated IX are equally plausible as the initiating protease for the extrinsic limb of blood coagulation, it might be appropriate to illustrate this key step of hemostasis as currently being unknown.

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