Abstract:
:Background Polycystic ovarian syndrome (PCOS) affects up to 18% of reproductive-aged women with increased risks of cardiovascular disease and venous thromboembolic disease, related to metabolic and hormonal features, obesity and an apparent hypofibrinolytic state, possibly exacerbated by current PCOS treatments. Objective To investigate and compare haemostatic impacts of common pharmacological treatments and explore relationships with hormonal and metabolic variables in PCOS. Patients/Methods This mechanistic sub-study using biobanked samples from a 6-month randomized comparative trial of pharmacological treatments assessed pro- and anti-thrombotic markers and overall haemostatic activity. Overweight women of mean age 33.9 ± 6.7 years and mean BMI (body mass index) of 36.5 ± 7.0 kg/m2 with PCOS (n = 60) were randomized to either metformin, higher-dose oral contraceptive pill (OCP) or low-dose OCP + spironolactone (OCP + S). Primary outcome measures included changes in plasminogen activator inhibitor 1 (PAI-1), asymmetric dimethylarginine (ADMA), prothrombin fragments 1 and 2 (PF1 and 2), plasminogen, tissue plasminogen activator (tPA), thrombin activatable fibrinolysis inhibitor (TAFI) and thrombin generation (TG). Results PAI-1 activity fell in all groups, ADMA fell in higher-dose OCP, PF1 and 2 increased with metformin and higher-dose OCP, TG rose and tPA fell in both OCP groups, plasminogen increased in all and TAFI increased after higher-dose OCP. Conclusion Endothelial function (primary haemostasis) improved with higher dose with some improvement in low-dose OCP + S and metformin. Aberrant coagulation was noted in both OCP groups, but not with metformin. Fibrinolysis was reduced with higher-dose OCP. Our work suggests an additional dimension of treatment (haemostatic system effects) that favours metformin treatment over the OCP in PCOS.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Burchall GF,Piva TJ,Ranasinha S,Teede HJdoi
10.1160/TH17-04-0248subject
Has Abstractpub_date
2017-11-01 00:00:00pages
2053-2062issue
11eissn
0340-6245issn
2567-689Xjournal_volume
117pub_type
杂志文章abstract::Catabolism of coagulation factor VIII (FVIII) is mediated by low-density lipoprotein receptor-related protein (LRP). The ligand-binding sites of LRP are formed by complement-type repeats (CR), and CR clusters II and IV bind most of LRP ligands. FVIII contains two major LRP-binding sites located in the A2 and A3 domain...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-12-01 00:00:00
abstract::The demographic and clinical characteristics of adults and children with lower extremity deep-vein thrombosis and/or pulmonary embolism (LE DVT/PE) may differ from those with abdominal vein thrombosis (abdominal VT). Abdominal VT can be a presenting sign of an underlying prothrombotic state, and its presence in the se...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH12-08-0568
更新日期:2013-04-01 00:00:00
abstract::A disintegrin and metalloproteases (ADAMs) are membrane-bound enzymes responsible for the shedding or cleavage of various cell surface molecules, such as adhesion molecules, cytokines/chemokines and growth factors. This shedding can result in the release of soluble proteins that can exert agonistic or antagonistic fun...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1660479
更新日期:2018-07-01 00:00:00
abstract::We report here on a patient whose abnormal fibrin clot was detected via the measurement of clot rigidity with a simple buoyant inner cylinder elastometer. The patient's clinical coagulation studies were all within normal limits except for prolonged thrombin and reptilase clotting times and high level of fibrin split p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1979-10-31 00:00:00
abstract::Although associated with adverse outcomes in other cardiopulmonary diseases, limited evidence exists on the prognostic value of anaemia in patients with acute pulmonary embolism (PE). We sought to examine the associations between anaemia and mortality and length of hospital stay in patients with PE. We evaluated 14,27...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH11-04-0208
更新日期:2011-08-01 00:00:00
abstract::Developmental haemostasis is a concept, now universally accepted, introduced by Andrew et al. in the late 1980's. However, coagulation analysers and reagents have changed significantly over the past 15 years. Coagulation testing is known to be sensitive to changes in individual reagents and analysers. We hypothesised ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-01-0047
更新日期:2006-02-01 00:00:00
abstract::ADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in 13% of them, is associated with pregnancy. However, there is little information on the protease behaviour in normal pregnancy. We studied von Willebrand factor and AD...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-11-0683
更新日期:2004-12-01 00:00:00
abstract::Activated protein C (APC) is a serine proteinase that regulates blood coagulation. In plasma it is inhibited mainly by the protein C inhibitor (PCI). The plasma concentrations of APC-PCI complex is increased in hypercoagulative states such as deep venous thrombosis. Formation of the APC-PCI complex induces a drastic c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00
abstract::Platelets and coagulation are involved in bacterial colonisation of the host. Streptocococcus pneumoniae (pneumococcus) are important etiologic agents of respiratory tract infections in humans. The formation of pneumococci-platelet associations may facilitate haematogenous dissemination of pneumococci by providing an ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-01-0049
更新日期:2009-10-01 00:00:00
abstract::ADP plays a crucial role in haemostasis and thrombosis and its receptors are potential targets for antithrombotic drugs. Two G-protein coupled P2 receptors contribute to platelet aggregation: the P2Y1 receptor initiates aggregation through mobilisation of calcium stores, while the more recently identified P2Y12 recept...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:2001-07-01 00:00:00
abstract::Thromboelastography (TEG) has been shown to be a valuable point-of-care device for the rapid diagnosis of various bleeding disorders. However, TEG has thus far not been used for the screening for von Willebrand disease (VWD). We evaluated the performance of a modified TEG assay for the laboratory screening of VWD. Thr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-12-0782
更新日期:2011-06-01 00:00:00
abstract::Fresh retracted clots are known to be poorly lysable by fibrinolytic agents. We have studied whether lysis of retracted clots could be enhanced by bulk transport in comparison to pure diffusion of plasma containing urokinase (400 IU/ml) into the clots. Cylindrical retracted blood clots were occlusively glued by a poly...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-12-07 00:00:00
abstract::The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH11-12-0899
更新日期:2012-09-01 00:00:00
abstract::Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG). We sought to determine the diagnostic validity of plasma biomarkers of i) inflammation (marked by interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]), ii) extracellular matrix remodelling (matrix metalloprot...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-12-0837
更新日期:2010-07-01 00:00:00
abstract::A preliminary clinical trial was conducted to determine the feasibility of achieving and regulating therapeutic anticoagulation with heparin given by continuous subcutaneous infusion. Five patients with deep venous thrombosis confirmed by impedance plethysmography and/or venography were studied. All patients received ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-02-26 00:00:00
abstract::The prothrombin time (PT) test is used to monitor oral anticoagulant therapy. Contact activation of patient blood samples in vitro may shorten the PT and thus lead to underestimation of the degree of anticoagulation. Commercial evacuated tubes for blood collection have been reported to induce shortening of the PT. The...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-10-31 00:00:00
abstract::Recently we prepared sulfated, low-molecular-weight lignins (LMWLs) to mimic the biological activities of heparin and heparan sulfate. Chemo-enzymatically prepared sulfated LMWLs represent a library of diverse non-sugar, aromatic molecules with structures radically different from the heparins, and have been found to p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-07-0454
更新日期:2010-03-01 00:00:00
abstract::Elevated plasma fibrinogen is a risk factor for cardiovascular disease (CVD), but associations between fibrinogen single nucleotide polymorphisms (SNPs) and disease risk are inconsistent. We investigated whether common (> or = 5% minor allele frequency) variation in the fibrinogen genes (FGA, FGB, FGG) is associated w...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH07-08-0523
更新日期:2008-02-01 00:00:00
abstract::Tissue factor is the primary initiator of coagulation cascade and plays an essential role in haemostasis and thrombosis. In addition, tissue factor and coagulation proteases contribute to many cellular responses via activation of protease activated receptors. The heart is an organ with high levels of constitutive tiss...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-03-0243
更新日期:2014-11-01 00:00:00
abstract::In this study, the clot accumulation properties of liposome-coupled plasminogen were compared to those of free (non-liposomal) plasminogen in an in vitro, closed-loop, flow-system. After introduction of a clot into the closed system, double-radiolabelled plasminogen-liposomes were administered and the accumulation of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::The synthetic peptide SFLLRNPNDKYEPF, identical in sequence to the new amino-terminus of the thrombin receptor generated following cleavage of thrombin, acts a thrombin receptor agonist/activating peptide (TRAP). In this study, Northern blot analysis showed that cultured human vascular smooth muscle cells (HVSMC) expr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Platelet activation plays a pivotal role in physiological hemostasis and pathological thrombosis causing heart attack and stroke. Previous studies conclude that simultaneous activation of Gi and G12/13 signaling pathways is sufficient to cause platelet aggregation. However, using Gq knockout mice and Gq-specific inhib...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1714745
更新日期:2020-11-01 00:00:00
abstract::This review collects evidence about immune and inflammatory functions of platelets from a clinician's point of view. A focus on clinically relevant immune functions aims at stimulating further research, because the complexity of platelet immunity is incompletely understood and not yet translated into patient care. Pla...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-02-0146
更新日期:2014-10-01 00:00:00
abstract::Recent meta-analyses indicate that low molecular weight heparins (LMWH) are more effective than unfractionated heparin (UH) in preventing and treating deep vein thrombosis. This article presents the arguments for and against the need for laboratory monitoring. At the present time, the only tests currently available fo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1994-09-01 00:00:00
abstract::Colorectal cancer (CRC) is a major cause of morbidity and mortality, and the composition of the tumour stroma is a strong predictor of survival in this cancer type. Tissue factor (TF) functions as the trigger of haemostasis together with its ligand coagulation factor VII/VIIa, and TF expression has been found in tumou...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-04-0267
更新日期:2016-11-30 00:00:00
abstract::We have recently reported the short-term intraindividual variability of several coagulation factors and inhibitors included in the ARIC study (Chambless et al. Ann Epidemiol 1992; 2:723). In this paper, we reported the intraindividual variability results of additional hemostatic factors. Blood samples were collected f...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::The contribution of the various components of the contact system in the generation of factor XIIa (FXIIa) and of kallikrein (KRN) on an electronegative surface and the release of the generated enzymes to the bulk phase was examined in mixtures of normal human plasma and plasmas congenitally deficient in these componen...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is mainly caused by dominant-negative mutations in the multimeric protein von Willebrand factor (VWF). These mutations may either result in quantitative or qualitative defects in VWF. VWF is an endothelial protein that is secreted to the c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1715442
更新日期:2020-11-01 00:00:00
abstract::Amniotic fluid inhibited the fibrinolytic, amidolytic and esterolytic activity of urokinase. Kinetic studies with AGLMe demonstrated non-competitive inhibition. A major part of the inhibitory activity could be separated from alpha 1-antitrypsin by ion-exchange chromatography on DEAE-Sephadex A-50. Plasminogen activato...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1980-08-29 00:00:00
abstract::A fibrinolysis inhibitor was purified in serum from post-traumatic patients by the use of flat bed electrofocusing of serum desalted by gel chromatography followed by affinity chromatography on a column of matrix-linked plasminogen. Disc gel electrophoresis yielded one protein band. The inhibitor protein was also foun...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-02-28 00:00:00