Journal of thrombosis and haemostasis : JTH最新文献

{"title":"Relationship between markers of activated coagulation, their correlation with inflammation, and association with coronary heart disease (NPHSII).","authors":"G. Miller, H. Ireland, J. Cooper, K. Bauer, J. Morrissey, S. Humphries, M. Esnouf","doi":"10.1111/J.1538-7836.2007.02819.X","DOIUrl":"https://doi.org/10.1111/J.1538-7836.2007.02819.X","url":null,"abstract":"OBJECTIVE\u0000To determine whether activation of coagulation increases in parallel with inflammation and whether coagulation activation markers (CAMs) are independently associated with coronary heart disease (CHD), in the prospective study, NPHSII.\u0000\u0000\u0000METHODS\u0000Surveillance of 2997 men between 50 and 63 years yielded 314 first CHD events during 36507 person-years of observation. The plasma levels of activated factor XII (FXIIa), the peptides released upon activation of factor X (FXpep) and factor IX (FIXpep), activated factor VII (FVIIa), prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FpA) served as indices of activity along the coagulation pathway. C reactive protein (CRP) provided a marker of inflammatory activity.\u0000\u0000\u0000RESULTS\u0000While borderline or significant correlations were identified for each CAM with inflammation, as determined by CRP levels, these did not reach as high a numerical value as was shown for fibrinogen with CRP. FVIIa and FIXpep possessed independent associations with CHD: a one SD increase in adjusted FIXpep and FVIIa level was associated with a relative hazard of 1.20 (95% CI 1.00-1.43) and 0.70 (CI 0.58-0.86), respectively, using a group including all CHD events, compared with 'no-event'.\u0000\u0000\u0000CONCLUSIONS\u0000Inflammation has significant but minimal impact upon CAMs of the extrinsic coagulation pathway. Reduced FVIIa and increased FIXpep levels were found to be significant, independent, predictors of CHD.","PeriodicalId":161374,"journal":{"name":"Journal of thrombosis and haemostasis : JTH","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2008-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125920528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of the enzymatic activity of activated coagulation factor IX by anti-factor IX antibodies.","authors":"F Scheiflinger,&nbsp;M Dockal,&nbsp;J Rosing,&nbsp;R J Kerschbaumer","doi":"10.1111/j.1538-7836.2007.02868.x","DOIUrl":"https://doi.org/10.1111/j.1538-7836.2007.02868.x","url":null,"abstract":"<p><strong>Background: </strong>Factor VIIIa (FVIIIa) binds to activated FIX and enhances the activation of FX by several orders of magnitude. Deficiency of FVIII causes the bleeding disorder hemophilia A and is treated by i.v. infusion of FVIII concentrates.</p><p><strong>Objectives: </strong>To explore whether or not FVIII activity can be supplied by alternative molecules, e.g. molecules with FIXa-binding activity.</p><p><strong>Methods: </strong>Conventional hybdridoma technology was used to discover antibodies exhibiting FVIII-like activity.</p><p><strong>Results: </strong>We identified a series of antibodies specific for human FIX that mimicked the stimulatory effect of FVIIIa on FIXa. Upon binding to human FIXa, these antibodies enhanced the protease activity of FIXa towards its natural substrate FX about tenfold. A similar enhancement was also achieved with 5 pm FVIIIa (i.e. 16 mU mL(-1) or 1.6% activated FVIII). Procoagulant activity of these anti-FIXa antibodies was observed in model systems containing purified proteins as well as in plasma.</p><p><strong>Conclusion: </strong>Our findings show that FVIII can, at least partially, be replaced by an unrelated molecule. Procoagulant antibodies might potentially aid the development of an FVIII substitute for hemophilia A treatment.</p>","PeriodicalId":161374,"journal":{"name":"Journal of thrombosis and haemostasis : JTH","volume":" ","pages":"315-22"},"PeriodicalIF":10.4,"publicationDate":"2008-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27125568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Talking about...clinic.","authors":"G Bruttomesso,&nbsp;N Miglino","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":161374,"journal":{"name":"Journal of thrombosis and haemostasis : JTH","volume":" ","pages":"1850-1"},"PeriodicalIF":10.4,"publicationDate":"2006-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26230493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary antiphospholipid syndrome in pregnancy: an analysis of outcome in a cohort of 33 women treated with a rigorous protocol.","authors":"S. Stone, B. Hunt, M. Khamashta, S. Bewley, C. Nelson-Piercy","doi":"10.1097/01.OGX.0000172317.50128.ED","DOIUrl":"https://doi.org/10.1097/01.OGX.0000172317.50128.ED","url":null,"abstract":"ABSTRACT Early recurrent miscarriage, placental insufficiency, intrauterine growth restriction (IUGR), and late fetal death all are possible consequences of primary antiphospholipid syndrome (APS). The authors undertook a prospective study of how best to manage APS pregnancies in 33 affected women who were pregnant. Nearly 80% of patients had a history of pregnancy-related morbidity and 36% had had thrombotic events. Four very premature live-born infants had died. One third of women had had three or more consecutive first-trimester miscarriages. A first-trimester ultrasound study was done to confirm viability and for accurate dating. Uterine artery Doppler waveform studies were done at 20 and 24 weeks gestation, and growth scans at monthly intervals starting at 24 to 26 weeks. The timing of delivery was individualized. Induction was recommended at 38 to 40 weeks gestation, although pregnancies were allowed to go beyond this if there were no complications. Operative delivery was done on obstetric indications. Aspirin and low-molecular-weight (LMW) heparin were given until labor began or until the day before planned delivery. Women taking warfarin were admitted 10 to 14 days before planned delivery and converted to either full-dose LMW heparin or intravenous unfractionated heparin up to the time of delivery. LMW heparin was continued after delivery when there was a history of venous thrombosis. The live birth weight in this series was 91%; there were only three failed pregnancies. Mean birth weight was 2853 g, and mean gestational age was 36.7 weeks. Complications included four cases of IUGR (two with concurrent preeclampsia), transient ischemic attacks in five women receiving LMW heparin, and one case of placental abruption. Renal function declined in one patient who had glomerular thrombotic microangiopathy. Lupus anticoagulant was the strongest predictive factor for a thrombotic event in pregnancy. Levels of anticardiolipin antibody were less predictive, but a past thrombotic event was a strong risk factor. A history of IUGR or fetal death predicted IUGR in the current pregnancy. The operative delivery rate in this series was 59%. This study shows that a very high live birth rate is achievable in women with primary APS who have a history of significant pregnancy-related morbidity and/or thrombosis.","PeriodicalId":161374,"journal":{"name":"Journal of thrombosis and haemostasis : JTH","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126959310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A highly-sensitive plasma von Willebrand factor ristocetin cofactor (VWF:RCo) activity assay by flow cytometry.","authors":"D. Chen, C. Daigh, J. I. Hendricksen, R. Pruthi, W. Nichols, J. Heit, W. Owen","doi":"10.1111/j.1538-7836.2007.02845.x","DOIUrl":"https://doi.org/10.1111/j.1538-7836.2007.02845.x","url":null,"abstract":"BACKGROUND\u0000Assays of plasma von Willebrand factor (VWF) ristocetin cofactor activity (VWF:RCo) are essential for the laboratory diagnosis of von Willebrand disease (VWD) and for monitoring therapy. However, current manual or automated VWF:RCo assay methods have relatively poor operating characteristics. Our goal was to develop and validate a simple, accurate, specific and sensitive platelet-based VWF:RCo assay.\u0000\u0000\u0000METHODS\u0000Using green or red fluorochrome-labeled, fixed normal platelets and normal or patient plasma, ristocetin-dependent and VWF-mediated platelet aggregation was detected by flow cytometry. VWF:RCo activity was assayed as the number of double-positive events (green and red) among all green or red events, relative to the calibrator plasma signal (6-150% or IU dL(-1)), and reported as percent or IU dL(-1). We tested plasma samples from normal donors (n = 51) and known VWD patients (type 1, n = 16; type 2, n = 17) based on clinical history, levels of plasma VWF antigen (VWF:Ag), VWF:RCo activity (manual platelet aggregometry/agglutination assay), factor (F) VIII activity and VWF multimer analysis.\u0000\u0000\u0000RESULTS\u0000For normal donors and type 1 VWD patients, VWF:RCo activity by flow cytometry vs. manual platelet aggregation correlated closely (R2 = 0.74), and VWF:RCo/VWF:Ag ratios did not differ significantly. In contrast, VWF:RCo/VWF:Ag ratios for type 2 VWD subtypes were significantly lower using VWF:RCo by flow cytometry vs. manual platelet aggregation assay (P < 0.01), especially for type 2A VWD patients.\u0000\u0000\u0000CONCLUSIONS\u0000This new flow cytometry-based VWF:RCo assay is simple, accurate, specific and sensitive, particularly for type 2 VWD.","PeriodicalId":161374,"journal":{"name":"Journal of thrombosis and haemostasis : JTH","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115405108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}