Rapid activation of haemostasis after hormonal emergency contraception

2007 ◽  
Vol 97 (01) ◽  
pp. 15-20 ◽  
Author(s):  
Angela Silveira ◽  
Stella Thomassen ◽  
Lars-Olof Hansson ◽  
Jan Rosing ◽  
Anders Hamsten ◽  
...  
Keyword(s):  
Emergency Contraception ◽  
Plasma Concentrations ◽  
Protein S ◽  
Sex Hormone Binding Globulin ◽  
Factor Vii ◽  
Coagulation System ◽  
Short Exposure ◽  
Apo B ◽  
Reactive Protein ◽  
Apc Resistance

SummaryHormonal emergency contraception (EC) is a well established contraceptive method, recommended to all women, although the effects on haemostais are not fully evaluated. The aim of this study was to evaluate whether exposure to EC has effects on well established cardiovascular risk factors, and also to examine whether differences exist between two EC treatments. In a prospective randomized cross over design 11 women used two different EC methods, one with estrogen and levonorgestrel (EE-EC) and one with levonorgestrel only (LNG-EC). Plasma concentrations of haemostatic factors (APC resistance, antithrombin, fibrinogen, prothrombin fragment 1+2, free protein S, factor VII and PAI-1), sex-hormone-binding globulin (SHBG), the apolipoprotein (apo)B/apoA1 ratio and C-reactive protein (CRP) were followed frequently during the following 48 h A rapid haemostatic activation was induced with both treatments, although more pronounced with EE-EC. Already two hours after EC, the plasma concentrations of haemostatic parameters and SHBG were significantly different from baseline concentrations. An ETP-based APC-resistance method showed increased APC resistance with EE-EC and decreased APC resistance with LNG-EC. The ApoB/ApoA1 ratio was affected in a favourable direction with EE-EC.CRP increased slightly regardless of treatment. Even a very short exposure to exogenous sex hormones causes prompt effects on hepatic protein synthesis and the coagulation system. This must be taken into consideration whenever exogenous steroid hormones are administered, especially to individuals with a genetic predisposition to thrombosis or transiently disturbed haemostasis.

scholarly journals Associations between dietary patterns and serum lipids, apo and C-reactive protein in an adult population: evidence from a multi-city cohort in South America

2017 ◽  
Vol 117 (4) ◽  
pp. 548-555 ◽  
Author(s):  
Rosana Poggio ◽  
Natalia Elorriaga ◽  
Laura Gutierrez ◽  
Vilma Irazola ◽  
Adolfo Rubinstein ◽  
...  
Keyword(s):  
South America ◽  
Total Cholesterol ◽  
Dietary Patterns ◽  
Ldl Cholesterol ◽  
Plasma Concentrations ◽  
Serum Total Cholesterol ◽  
C Reactive Protein ◽  
Apo B ◽  
Reactive Protein ◽  
Hs Crp

AbstractSeveral previous epidemiological studies from developed countries have shown that an unhealthy dietary pattern affects plasma lipid levels and inflammation biomarkers. We assessed the cross-sectional associations between dietary patterns and cardiovascular risk factors among 961 adults from a multi-city cohort in South America. We conducted a principal component analysis to derive dietary patterns. As outcomes, we examined plasma levels of apo A-I, apo B, high-sensitivity C-reactive protein (hs-CRP), LDL-, HDL- and serum total cholesterol and TAG. The crude and adjusted changes in each outcome were estimated for quartiles of dietary patterns using multivariable linear regression models. The prudent pattern (PP) characterised by higher intake of fruits, vegetables, fish, seafood, whole cereal and low-fat dairy products was associated with reduced plasma concentrations of apo B (−8·5 mg/l), total cholesterol (−18·8 mg/dl) and LDL-cholesterol (−16·5 mg/dl) and hs-CRP (−1·6 mg/l) in men. In women also reduced plasma concentrations of apo B (−6·6 mg/l), total (−12·0 mg/dl) and LDL (−9·3 mg/dl). The ‘Western-like’ pattern characterised by higher intake of eggs, pastry and cakes, pizza, snacks, refined grains, red meat, vegetable oils and poultry was not significantly associated with any of the selected serum lipid or inflammatory biomarkers. The explained variances were 10·3 and 7·4 %, respectively. The PP was associated with better lipid profile, mainly lower atherogenic particles (apo B) and LDL-cholesterol and serum total cholesterol. This study provides possible evidence of a prudent diet in South American populations to help reduce the burden of CVD.

Two Common Functional Polymorphisms in the Promoter Region of the Coagulation Factor VII Gene Determining Plasma Factor VII Activity and Mass Concentration

Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3432-3441 ◽  
Author(s):  
Ferdinand M. van ’t Hooft ◽  
Angela Silveira ◽  
Per Tornvall ◽  
Anastasia Iliadou ◽  
Ewa Ehrenborg ◽  
...  
Keyword(s):  
Promoter Region ◽  
Nuclear Protein ◽  
Plasma Concentrations ◽  
Coagulation Factor ◽  
Protein S ◽  
Factor Vii ◽  
Binding Properties ◽  
Coagulation Factor Vii ◽  
Functional Polymorphisms ◽  
Plasma Factor

Recent studies have provided evidence for associations between common polymorphic markers in the coagulation factor VII (FVII) gene and plasma FVII levels. Here we describe two common, nonrelated, functional polymorphisms in the promoter region of the FVII gene, a G to T substitution at position −401 and a novel G to A substitution at position −402. Both polymorphisms strongly influence the binding properties of nuclear protein(s). The rare −401T allele is associated with a reduced basal rate of transcription of the FVII gene in human hepatoblastoma cells and with reduced plasma concentrations of total FVII (VIIag) and fully activated FVII molecules (VIIa). In contrast, the rare −402A allele confers increased transcriptional activity and is associated with increased plasma FVII levels. Together, the two polymorphisms explained 18% and 28% of the variation in VIIag and VIIa, respectively, in a group of 183 healthy, middle-aged men. It is concluded that these polymorphisms are important for the regulation of the plasma levels of FVII and that they are likely to be useful genetic markers to resolve the issue of whether a causal relationship exists between FVII levels and risk of coronary heart disease.

Abstract 350: Influence of HIV-1 Infection and Antiretroviral Therapy on the Coagulation System

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Kevin Fasing ◽  
Brian R Weil ◽  
Kyle J Diehl ◽  
Jared J Greiner ◽  
Brian L Stauffer ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Factor Viii ◽  
Tissue Factor ◽  
Plasma Concentrations ◽  
Tissue Type ◽  
Factor Vii ◽  
Coagulation System ◽  
Factor X ◽  
Thrombotic Risk ◽  
Hiv 1

HIV-1-infected individuals have a two- to four-fold greater incidence of cardiovascular disease and atherothrombotic events compared with the general population. The mechanisms responsible for this heightened cardiovascular risk are not fully understood. We have previously reported that the capacity of the endothelium to release tissue-type plasminogen activator (t-PA), the primary activator of fibrinolysis and a key endogenous defense mechanism against intravascular fibrin deposition and thrombosis, is impaired in HIV-1-seropositive adults. Whether diminished fibrinolytic activity is coupled with a hypercoagulative state in this population is unknown. Elevations in specific coagulation markers such as tissue factor and Factor VII are associated with increased thrombotic risk. The experimental aim of this study was to determine the influence of HIV-1 infection and antiretroviral therapy (ART) on markers of coagulation. To address this aim we studied 33 men: 16 HIV-1-seronegative (age: 41±3 yr); 7 HIV-1-seropositive treatment-naïve (34±2 yr); and 10 HIV-1-seropositive receiving ART (42±3 yr; efavirenz-based regimen). All subjects were non-obese, normotensive and free of overt cardiometabolic disease. Circulating concentrations of tissue factor, Factor VII, Factor VIII and Factor X were determined by immunoassay. There were no significant differences in plasma concentrations of tissue factor (32+3 vs 40+3 pg/mL), Factor VII (103+9 vs 100+5 %), Factor VIII (111+13 vs 117+8 %) and Factor X (89+5 vs 91+2 %) between HIV-1-seropositive treatment-naïve and healthy men. Moreover, there was no influence of ART on these circulating markers. Plasma tissue factor (41+5 pg/mL), Factor VII (107+6 %), Factor VIII (103+7 %) and Factor X (90+3%) were similar in the HIV-1-seropositive receiving ART compared with HIV-1-seropositive treatment-naïve and seronegative groups. These data suggest that neither HIV-1 infection per se nor ART are associated with unfavorable changes in specific coagulation markers. Thus, changes in the coagulation system that have been linked to increased thrombotic burden are not apparent in HIV-1-seropositive adults.

scholarly journals Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Postpartum Health in Project Viva: A Prospective Cohort

2020 ◽  
Vol 105 (9) ◽  
pp. e3415-e3426
Author(s):  
Susanna D Mitro ◽  
Sharon K Sagiv ◽  
Abby F Fleisch ◽  
Lindsay M Jaacks ◽  
Paige L Williams ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Prospective Cohort ◽  
Plasma Concentrations ◽  
Environmental Chemicals ◽  
Sex Hormone Binding Globulin ◽  
Blood Biomarkers ◽  
Reactive Protein ◽  
Perfluorooctane Sulfonamide ◽  
Cardiometabolic Markers ◽  
Mid Upper Arm Circumference

Abstract Context Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes. Objective We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers. Design, Patients, and Measures We studied women recruited between 1999 and 2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA). Three-year postpartum anthropometry measurements were available from 786 to 801 women, blood pressure from 761 women, and blood biomarkers from 450 to 454 women. We used multivariable regression to evaluate the association of log2-transformed PFAS with postpartum anthropometry, blood pressure, and blood biomarkers (leptin, adiponectin, sex hormone binding globulin [SHBG], hemoglobin A1c, interleukin-6 [IL-6], C-reactive protein), adjusting for age, prepregnancy body mass index, marital status, race/ethnicity, education, income, smoking, parity, and breastfeeding history. Results Pregnancy concentrations of certain PFAS were associated with greater adiposity (eg, 0.4 cm [95% confidence interval [95%CI]: −0.1, 0.9] greater waist circumference per doubling in EtFOSAA; 0.2 cm [95%CI: −0.1, 0.5] greater mid-upper arm circumference per doubling in PFOA; 1.2 mm [95%CI: 0.1, 2.2] thicker sum of subscapular and triceps skinfolds per doubling in PFOS) and higher systolic blood pressure (eg, 1.2 mm Hg [95%CI: 0.3, 2.2] per doubling in PFOS) at 3 years postpartum. Higher EtFOSAA concentrations were also associated with 10.8% higher IL-6 (95%CI: 3.3, 18.9) and 6.1% lower SHBG (95%CI: 0.7, 11.2) per doubling. Conclusions Pregnancy concentrations of EtFOSAA, PFOS, and PFOA were associated with adverse postpartum cardiometabolic markers.

A Novel Thrombomodulin Gene Mutation in a Patient Suffering from Sagittal Sinus Thrombosis

1997 ◽  
Vol 78 (04) ◽  
pp. 1164-1166 ◽  
Author(s):  
Lena Norlund ◽  
Bengt Zöller ◽  
Ann-Kristin Öhlin
Keyword(s):  
Protein C ◽  
Sinus Thrombosis ◽  
Activated Protein C ◽  
Protein S ◽  
Thromboembolic Disease ◽  
Coagulation System ◽  
Sagittal Sinus ◽  
Apc Resistance ◽  
American Patient ◽  
Sagittal Sinus Thrombosis

SummaryThrombomodulin is an endothelial cell membrane glycoprotein that promotes protein C activation. It has been clearly demonstrated that the anticoagulant functions of the protein C system are important in the prevention of thromboembolic disease. Patients with protein C or protein S deficiency and/or resistance to activated protein C (APC resistance) are at higher risk for developing thromboembolic disease. The first mutation in the thrombomodulin gene was discovered in an American patient suffering from pulmonary embolism at the age of 45 (Öhlin and Marlar 1995). Here we report a case of sagittal sinus thrombosis in a 42-year-old Swedish woman. She was found to carry a heterozygous point mutation changing G127 to A, predicting an Ala25 to a Thr change in the mature thrombomodulin protein. This mutation was also found in her 16-year-old daughter, who so far has not suffered from any thrombotic events. The patient had no other detectable prothrombotic genetic defects associated with the coagulation system. This case supports the hypothesis of an association between mutations in the thrombomodulin gene and venous thrombosis.

scholarly journals Elevated Complement C3 and C4 Levels are Associated with Postnatal Pregnancy-Related Venous Thrombosis

2019 ◽  
Vol 119 (09) ◽  
pp. 1481-1488
Author(s):  
Anders E. A. Dahm ◽  
Eva Marie Jacobsen ◽  
Hilde Skuterud Wik ◽  
Anne Flem Jacobsen ◽  
Tom Eirik Mollnes ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Protein S ◽  
Coagulation Factors ◽  
Complement C3 ◽  
Coagulation System ◽  
C Protein ◽  
Reactive Protein ◽  
Coagulation Inhibitors ◽  
Tissue Factor Pathway ◽  
Control Study

AbstractHigh levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with pregnancy-related VT. We undertook the Norwegian VIP study, a case–control study of VT in pregnancy or within 3 months postpartum (cases, n = 313) and women without pregnancy-related VT (controls, n = 353). Determinants of C3 and C4 in the control women were investigated with linear regression and the odds ratio (OR) for pregnancy-related VT was calculated with logistic regression. We found that levels of C3 and C4 were associated with body mass index (BMI), C-reactive protein (CRP); with the coagulation factors (F) fibrinogen, FVIII, and FIX; and with the coagulation inhibitors antithrombin, protein C, protein S, and tissue factor pathway inhibitor. These associations were influenced by CRP levels. The crude OR for pregnancy-related VT was 1.8 (95% confidence interval [CI], 1.1–3.0) for C3 above the 90th percentile and 2.0 (95% CI, 1.2–3.2) for C4 above the 90th percentile. Stratification in antenatal and postnatal VT showed that C3 and C4 were only associated with postnatal VT with an OR for high C3 of 3.0 (95% CI, 1.8–5.0), and for high C4 of 2.6 (95% CI, 1.5–4.6). Adjustment for high FIX and BMI reduced the ORs. We conclude that the association between postnatal VT and C3 and C4 suggests that there is clinically relevant crosstalk between the complement and the coagulation system.

scholarly journals Factor IXa-factor VIIIa-cell surface complex does not contribute to the basal activation of the coagulation mechanism in vivo

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2039-2047 ◽  
Author(s):  
KA Bauer ◽  
PM Mannucci ◽  
A Gringeri ◽  
F Tradati ◽  
S Barzegar ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Concentrations ◽  
Factor Ix ◽  
Factor Vii ◽  
Coagulation System ◽  
Activate Factor ◽  
Factor X ◽  
Factor Ixa ◽  
Tissue Factor Pathway ◽  
Activation Peptide

Abstract We have infused recombinant factor VIIa into patients with hereditary factor VII deficiency with marked reductions in plasma concentrations of factor IX activation peptide (FIXP), factor X activation peptide (FXP), and prothrombin activation fragment F1+2. These investigations show substantial elevations in these markers of coagulation activation and thereby demonstrate that the factor VII-tissue factor pathway is largely responsible for the activation of factor IX as well as factor X in the basal state (ie, the absence of thrombosis or provocative stimuli). We have administered a monoclonal antibody purified factor IX concentrate to individuals with hemophilia B. These studies show an increase in the plasma levels of FIXP that were initially greatly decreased, but no change in FXP or F1+2. We have also infused highly purified factor VIII concentrate into patients with hemophilia A. The data demonstrate no significant changes in the plasma concentrations of FXP and F1+2. The above observations indicate that factor IXa generated by the factor VII-tissue factor pathway is unable to activate factor X under basal conditions. Based upon the above findings, we outline a model of blood coagulation system function under basal conditions, and suggest a process by which the generation of factor Xa and thrombin might be accelerated during normal hemostasis and in the setting of thrombotic disorders.

Different Effects of Oral and Transdermal Hormone Replacement Therapies on Factor IX, APC Resistance, t-PA, PAI and C-reactive Protein

2001 ◽  
Vol 86 (08) ◽  
pp. 550-556 ◽  
Author(s):  
Mark Upton ◽  
Ann Rumley ◽  
Alex McConnachie ◽  
Denis O’Reilly ◽  
Graham Watt ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Inflammatory Marker ◽  
Hormone Replacement ◽  
Menopausal Status ◽  
Factor Ix ◽  
Factor Vii ◽  
C Reactive Protein ◽  
Thrombotic Risk ◽  
Reactive Protein ◽  
Apc Resistance

SummaryThe effects of hormone replacement therapy (HRT) on thrombosis risk, thrombotic variables, and the inflammatory marker C-reactive protein (CRP) may vary by route of administration (oral versus transdermal). We studied the relationships of 14 thrombotic variables (previously related to cardiovascular risk) and CRP to menopausal status and to use of HRT subtypes in a cross-sectional study of 975 women aged 40-59 years. Our study confirmed previously-reported associations between thrombotic variables and menopausal status. Oral HRT use was associated with increased plasma levels of Factor IX, activated protein C (APC) resistance, and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity. Factor VII levels were higher in women taking unopposed oral oestrogen HRT. The foregoing associations were not observed in users of transdermal HRT; hence they may be consequences of the “first-pass” effect of oral oestrogens on hepatic protein synthesis. We conclude that different effects of oral and transdermal HRT on thrombotic and inflammatory variables may be relevant to their relative thrombotic risk; and suggest that this hypothesis should be tested in prospective, randomised studies.

scholarly journals Factor IXa-factor VIIIa-cell surface complex does not contribute to the basal activation of the coagulation mechanism in vivo

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2039-2047
Author(s):  
KA Bauer ◽  
PM Mannucci ◽  
A Gringeri ◽  
F Tradati ◽  
S Barzegar ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Concentrations ◽  
Factor Ix ◽  
Factor Vii ◽  
Coagulation System ◽  
Activate Factor ◽  
Factor X ◽  
Factor Ixa ◽  
Tissue Factor Pathway ◽  
Activation Peptide

We have infused recombinant factor VIIa into patients with hereditary factor VII deficiency with marked reductions in plasma concentrations of factor IX activation peptide (FIXP), factor X activation peptide (FXP), and prothrombin activation fragment F1+2. These investigations show substantial elevations in these markers of coagulation activation and thereby demonstrate that the factor VII-tissue factor pathway is largely responsible for the activation of factor IX as well as factor X in the basal state (ie, the absence of thrombosis or provocative stimuli). We have administered a monoclonal antibody purified factor IX concentrate to individuals with hemophilia B. These studies show an increase in the plasma levels of FIXP that were initially greatly decreased, but no change in FXP or F1+2. We have also infused highly purified factor VIII concentrate into patients with hemophilia A. The data demonstrate no significant changes in the plasma concentrations of FXP and F1+2. The above observations indicate that factor IXa generated by the factor VII-tissue factor pathway is unable to activate factor X under basal conditions. Based upon the above findings, we outline a model of blood coagulation system function under basal conditions, and suggest a process by which the generation of factor Xa and thrombin might be accelerated during normal hemostasis and in the setting of thrombotic disorders.

Very Low Activated Factor VII and Reduced Factor VII Antigen in Familial Abetalipoproteinaemia

1998 ◽  
Vol 80 (08) ◽  
pp. 233-238 ◽  
Author(s):  
K. A. Mitropoulos ◽  
M. N. Nanjee ◽  
D. J. Howarth ◽  
J. C. Martin ◽  
M. P. Esnouf ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Positive Association ◽  
Factor Ix ◽  
Factor Vii ◽  
Unesterified Fatty Acid ◽  
Factor Xii ◽  
Factor X ◽  
Factor Xi ◽  
Activated Factor Vii ◽  
Normal Mean

SummaryAbetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyce-ride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 μmol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients’ mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

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