| 1. |
- Agewall, S, et al.
(författare)
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Insulin sensitivity and hemostatic factors in clinically healthy 58-year-old men.
- 2000
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 84:4, s. 571-5
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this cross-sectional study was to investigate the relationship between factors of the coagulation- and fibrinolysis systems and insulin sensitivity in 104 clinically healthy, 58-years-old men. Insulin sensitivity (hyperinsulinemic euglycemic clamp) adjusted for lean body mass, the metabolic syndrome according to a suggested definition, and different factors in the coagulation- and fibrinolysis system were determined. Subjects with the metabolic syndrome were characterised by increases in PAI-1 activity, tPA antigen, protein C and protein S and low concentrations of tPA activity. Insulin sensitivity was independently and reversibly associated with PAI-1 (p = 0.014) and directly with tPA activity (p = 0.001). Insulin sensitivity was also significantly negatively associated with protein S and protein C and several components in the metabolic syndrome, however not remaining significant in multivariate analyses. Protein C and protein S were significantly associated with PAI-1 activity, tPA activity (negatively), tPA antigen and antithrombin III. In conclusion, the data indicated that insulin resistance and several of the clustering components in the metabolic syndrome are accompanied by increased plasma concentrations of the anticoagulatory proteins C and S which may represent a mechanism which counteracts the concomitantly occurring hypofibrinolysis.
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| 2. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure
- 2004
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 92:6, s. 1250-1258
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Tidskriftsartikel (refereegranskat)abstract
- D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerning increased risk of cardiovascular mortality in an elderly population with symptoms associated with heart failure. A cardiologist examined 458 elderly patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed NYHA functional class and cardiac function. Abnormal systolic function was defined as EF <40% on Doppler echocardiography. Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer were analysed. D-dimer was analysed using an automated micro-latex assay. A statistical analysis was performed to identify the prognostic value of increased plasma concentration of D-dimer. Results showed that during a median follow-up period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for cardiovascular mortality that may be used to risk-stratify patients with heart failure. © 2004 Schattauer GmbH, Stuttgart.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Bokarewa, Maria, 1963, et al.
(författare)
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Human alpha -defensins neutralize fibrinolytic activity exerted by staphylokinase
- 2004
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Ingår i: Thromb Haemost. - 0340-6245. ; 91:5, s. 991-9
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Tidskriftsartikel (refereegranskat)abstract
- Defensins, cationic peptides with bacteriolytic properties, are abundantly found at inflammation sites and in human coronary vessels. Vascular occlusive diseases, such as myocardial infarction, pulmonary embolism, and peripheral arterial occlusion are presently treated by thrombolytic intervention using staphylokinase, a plasminogen activator of bacterial origin. In this study we assessed a possible interaction between defensins and staphylokinase, both molecules being present in an acutely ill patient. Using an ELISA-based system, we found that staphylokinase and defensins displayed a strong and dose-dependent binding. In contrast, urokinase, another plasminogen activator of endogenous origin, displayed only minimal binding to defensins. Next, we proved that interaction between staphylokinase and defensins led to functional consequences resulting in a significant decrease (p<0.002) of plasminogen activation capacity upon complex formation. In contrast, urokinase retained most of its activity even in 10-fold molar excess of defensins. Finally, we found that staphylokinase-triggered lysis of fibrin was efficiently inhibited in the presence of defensins. To assess structural requirements for staphylokinase/defensin interaction, six staphylokinase mutant variants were studied. Inactivation pattern of the tested staphylokinase variants suggested a direct binding of defensins to serine protease-like domain of staphylokinase. In conclusion, we show complex formation between staphylokinase and alpha-defensins resulting in a significant reduction of fibrinolytic activity. This finding may have clinical implications, since fibrinolytic effects of staphylokinase may be downregulated at the site of vascular occlusion.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Fälker, Knut, 1971-, et al.
(författare)
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ADP secretion and subsequent P2Y12 receptor signalling play a crucial role in thrombin-induced ERK2 activation in human platelets
- 2004
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Ingår i: Thrombosis and Haemostasis. - Stuttgart, Germany : Schattauer Gmbh. - 0340-6245 .- 2567-689X. ; 92:1, s. 114-23
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Tidskriftsartikel (refereegranskat)abstract
- Stimulating human platelets with thrombin induces the activation of the extracellular signal-regulated kinase 2 (ERK2). We demonstrate that this effect is highly dependent on ADP secretion and P2Y12 receptor signalling. AR-C69931MX (10 microM), a specific antagonist of the Gi-coupled P2Y12 ADP receptor, inhibits ERK2 activation induced by thrombin. Antagonists of the Gq-coupled P2Y1 ADP receptor, A3P5P (500 microM) and MRS2179 (100 microM), have no effect. ADP and its more potent analogue 2-methylthio-ADP alone (both up to 100 microM) do not induce ERK2 activation. Furthermore, we show that the inhibitory effect of AR-C69931MX on ERK2 activation induced by 0.1 U/ml thrombin as well as on platelet aggregation can be bypassed by epinephrine (1 and 10 microM), whereas epinephrine alone has no effect. Epinephrine acts on platelets mainly via alpha(2A)-adrenergic receptors, which, like P2Y12 receptors, couple to inhibitory G proteins. In addition, 2-methylthio-ADP as well as epinephrine provoke ERK2 activation at a thrombin concentration that alone has no detectable effect (0.05 U/ml). Thromboxane A2 (TXA2), which, like ADP, is released by activated platelets, acts as a positive feedback mediator. Stimulating the Gq-coupled TXA2 -receptor with U46619 (10 microM), which leads to ADP secretion and P2Y12 receptor-dependent platelet aggregation, also induces P2Y12-related ERK2 activation. The inhibition of U46619-induced ERK2 activation and platelet aggregation by AR-C69931MX are also rescued by epinephrine. Pretreatment with aspirin inhibits ERK2 activation induced by 0.1 U/ml thrombin, but has no effect at high concentrations of thrombin. The combination of U46619 and thrombin, at concentrations which alone have no effect, provokes ERK2 activation, suggesting that thrombin and released TXA2 act synergistically. Our data indicate that both primary signalling through Gq, which evokes ADP secretion, as well as subsequent coupling via Gi by the P2Y12 receptor are required for ERK2 activation.
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| 16. |
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| 17. |
- Herlitz, Hans, 1946, et al.
(författare)
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Erythrocyte sodium/lithium countertransport is associated with thrombotic and fibrinolytic factors in 58-year-old men
- 2004
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Ingår i: Thromb Haemost. - 0340-6245. ; 91:6, s. 1152-7
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Tidskriftsartikel (refereegranskat)abstract
- The metabolic syndrome, in which insulin resistance is the core feature, is associated both with dysregulation of thrombosis/fibrinolysis and erythrocyte sodium/lithium countertransport (SLC). To investigate this further we designed a cross-sectional study to examine whether factors involved in coagulation- and fibrinolysis systems were associated with SLC independently of insulin resistance in 93 58-year-old men. SLC was in univariate analysis positively correlated with PAI-1 activity (r = 0.35, p <0.01), tPA antigen (r = 0.38, p <0.01), von Willebrand factor (r = 0.25, p <0.05), protein S (r = 0.26, p <0.05), and C (r = 0.30, p <0.01), and negatively associated with tPA activity(r = -0.28, p <0.01). Since these correlations could be influenced by the components of the metabolic syndrome itself, a separate analysis with adjustment for glucose infusion rate (GIR), plasma insulin, body fat, sagittal diameter of the abdomen (SD) and log serum triglyceride concentration (TG) was conducted. Then SLC was associated with tPA antigen independent of GIR, plasma insulin, body fat, SD and TG. SLC was also associated with protein C independent of GIR, insulin, body fat and SD but not TG. In conclusion, we found a relationship between SLC and the fibrinolytic system that was not related to the metabolic syndrome.
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| 18. |
- Hillarp, Andreas, et al.
(författare)
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Local INR calibration of the Owren type prothrombin assay greatly improves the intra- and interlaboratory variation
- 2004
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 91:2, s. 300-307
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Tidskriftsartikel (refereegranskat)abstract
- In 1999, a simplified procedure for calibration of the Owren prothrombin time (Owren PT) assay was introduced by a working group of the organisation for national quality assurance in laboratory medicine in Sweden. The new protocol allowed local calibration by means of only two lyophilised national plasma calibrators and expression of results as an international normalized ratio (INR). This is our report of a three-year follow-up involving the analysis of data from all laboratories, in hospitals (n=88 in 2002) and primary health care units (n=246 in 2002) that perform the Owren PT assay in Sweden. The interlaboratory variation was significantly improved after the introduction of the new calibration procedure. For the larger hospital-based laboratories, the mean coefficient of variation (CV) was reduced from 7.9% to 5.2% (p<0.0001) when analysing test materials with INR range 2-4. In the higher INR range (>4), the CV was reduced even further, from 10.4% to 6.8% (p<0.0001). The corresponding results from smaller laboratories in the primary health care units showed a similar decrease in CV from 8.2% to 5.7% in the INR range 2-4 (p<0.0001). At the INR range >4, the CV was reduced from 9.5% to 7.8%. The intralaboratory variation was also improved for both types of laboratory categories. This study shows an improved precision, with CV less than 6% at the therapeutic INR range, for both hospital-based laboratories and smaller laboratories in the primary health care system. The results indicate that the Owren PT assay is well suited for local INR calibration employing only two calibrant plasmas in a simplified procedure.
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| 19. |
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| 20. |
- Hrafnkelsdottir, Thórdís, et al.
(författare)
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Extracellular nucleotides ATP and UTP induce a marked acute release of tissue-type plasminogen activator in vivo in man
- 2001
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 85:5, s. 875-881
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular nucleotides such as ATP and UTP are released by activation of platelets and ischemic tissue injury. The aim of the present study was to investigate whether ATP and UTP can induce acute tPA release from the vascular endothelium in vivo. Nine healthy subjects were studied in a perfused-forearm model during stepwise intraarterial infusions of ATP and UTP (10-200 nmol/min), and UTP during inhibition of prostanoid and NO synthesis by indomethacin and L-NMMA. ATP and UTP induced a similar and marked stimulation of forearm tPA release which increased 11- and 18-fold above baseline (p < or =0.01 for both) in conjunction with pronounced vasodilation. Neither the acute tPA release nor the vasodilation could be abrogated by NO and prostanoid synthesis inhibition. The similar effect of ATP and UTP suggests that P2Y rather than adenosine receptors mediate the response. Release of extracellular nucleotides in ischemic tissue may induce a pronounced activation of the endogenous fibrinolytic system.
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| 21. |
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| 22. |
- Jern, Christina, 1962, et al.
(författare)
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Evidence of a net release of tissue-type plasminogen activator across the human cerebral vasculature.
- 2004
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 91:5, s. 1019-25
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Tidskriftsartikel (refereegranskat)abstract
- We have earlier described models for measuring local net release rates of tissue-type plasminogen activator (t-PA) in vivo across skeletal, coronary, pulmonary, and splanchnic vascular beds. Aim of the present study was to investigate whether there is a net release of t-PA across the human cerebral vascular bed and whether an acute regulated release can be induced by sympathoadrenal activation. Fourteen male subjects undergoing elective coronary artery bypass grafting were investigated prior to surgery and during sternotomy-induced sympathoadrenal activation. Blood samples were obtained simultaneously from the radial artery and the jugular bulb. Blood flow velocity in the middle cerebral artery (V(MCA)) was determined by transcranial Doppler. Cerebral net release of t-PA was calculated as the arterio-venous concentration gradient times V(MCA). Prior to surgery there was a significant cerebral net release of t-PA (131 and 42 ng/min for t-PA antigen and activity, respectively). The release was significantly induced by sternotomy (to 271 and 80 ng/min, respectively). No significant cerebral net release of plasminogen activator inhibitor type 1 (PAI-1) was detected throughout the experiment. The results show that there is a basal net release of t-PA across the human cerebral vascular bed and that sympathoadrenal activation induces a local regulated release of t-PA.
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| 23. |
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| 24. |
- Klenner, Anne F, et al.
(författare)
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Heparin-induced thrombocytopenia in children : 12 new cases and review of the literature.
- 2004
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 91:4, s. 719-24
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated heparin-induced thrombocytopenia (HIT) is a rare but severe adverse effect of heparin therapy. Only few data are available on clinical presentation, diagnosis and management of HIT in children. Records of all patients sent to our laboratory between 1995 and November 2003 were reviewed. To identify literature reports a Medline search was performed, the reference lists of those publications were screened and the abstracts of meetings on thrombosis and hemostasis between 2000 and 2003 were assessed. We identified 12 new HIT patients between 13 months and 18 years of age from our laboratory and 71 reports on HIT in children in the literature. For the assessment of frequency of HIT all studies enrolling > 100 patients were analyzed. HIT is rare in children. In pediatric patients, there seem to be two risk groups: newborns and infants under 4 years of age undergoing cardiac surgery (incidence approximately 1-2%), and teenagers treated with heparin for thrombosis. For confirmation of HIT in children, antigen assays are most important. There are conflicting data on the optimal cut-off, with one randomized, double-blind trial indicating that the cut-off established in adults is appropriate. There are no systematic studies on alternative anticoagulants in children affected by HIT. Most data are available for lepirudin and danaparoid. Substitution of unfractionated heparin by low-molecular-weight heparins for regular anticoagulation may reduce the incidence of HIT.
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| 25. |
- Ladenvall, Per, 1972, et al.
(författare)
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Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated with a first myocardial infarction.
- 2002
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 87:1, s. 105-9
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Tidskriftsartikel (refereegranskat)abstract
- We recently identified a polymorphic Sp1 binding site in an enhancer at the tissue-type plasminogen activator (tPA) locus (tPA -7,351C/T), which was associated with vascular tPA release. Subjects homozygous for the -7,351C allele had twice the tPA release rate compared to subjects carrying the -7,351T allele. In this study we tested the hypothesis that the tPA -7,351C/T polymorphism is associated with myocardial infarction (MI). In a population-based prospective nested case-control study within northern Sweden, genotypes were determined among 61 MI cases and 120 controls. In a multivariate model, the tPA -7,351C/T polymorphism (OR 2.68 for T allele carriers; 95% CI 1.31-5.50), tPA antigen (OR 1.16; 95% CI 1.07-1.25) and apo A-I (OR, 0.997; 95% CI 0.995-0.999) were independently associated with a first MI. These findings suggest that genetic markers of local tPA release and circulating steady-state tPA levels carry independent prognostic information.
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| 26. |
- Leander, Karin, et al.
(författare)
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PAI-1 level and the PAI-1 4G/5G polymorphism in relation to risk of non-fatal myocardial infarction : results from the Stockholm Heart Epidemiology Program (SHEEP).
- 2003
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 89:6, s. 1064-71
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Tidskriftsartikel (refereegranskat)abstract
- This study examines the relationship between plasma Plasminogen Activator Inhibitor-1 (PAI-1) activity and the PAI-1 4G/5G polymorphism, and their association with the risk of myocardial infarction (MI). Furthermore, this study explores whether a high level of PAI-1 or whether the PAI-1 4G/5G polymorphism synergistically interacts with any established environmental risk factor for MI. This case-referent study of subjects aged 45-70 and living in Stockholm includes 851 men and 361 women with first-time MI and 1051 men and 505 women who were randomly chosen as referents from a population register. The adjusted odds ratio (OR) of MI was 1.9 (95% confidence interval [CI] 1.4-2.8) for men with a plasma PAI-1 activity level greater than the 90 th percentile value of referents. The corresponding OR for women was 1.5 (95% CI 0.9-2.5). A strong indication of synergistic interaction was found in men for the co-exposure to high plasma PAI-1 activity and current smoking, an adjusted synergy index score of 3.9 (95% CI 1.2-13.2). In women, the 4G allele was associated slightly with an increased risk of MI, OR 1.4 (95% CI 1.0-1.9). This association was not found in men. There were no clear indications of synergistic interaction effects involving the PAI-1 4G/5G polymorphism and the environmental exposures considered (cigarette smoking, physical inactivity, overweight, diabetes mellitus, hypercholesterolaemia, hypertension, high C-reactive protein and hypertriglyceridaemia).
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| 27. |
- Lethagen, Stefan, et al.
(författare)
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Von Willebrand's disease caused by compound heterozygosity for a substitution mutation (T1156M) in the D3 domain of the von Willebrand factor and a stop mutation (Q2470X).
- 2002
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 88:3, s. 421-426
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary defects of the von Willebrand factor (VWF) gene cause von Willebrand's disease (VWD) which shows great variability dependent on the nature and location of the mutation. We here describe the characteristics of a substitution of methionine for threonine 1156 in the D3 domain of the VWF, i.e. the domain involved in the intracellular multimerization of pro-VWF dimers. A VWD patient withsevere symptoms was a compound heterozygote for the T1156M mutation and a null allele (Q2470X) on the other chromosome. This led to marked reduction of plasma VWF concentration to about 0.05 U/ml and an abnormality of VWF multimers as in type 2A VWD. Expression in vitro of the mutation demonstrated that 1156M-VWF is secreted from COS-7 cells in a much reduced amount and lacking large multimers. When co-expressed with normal VWF 1156M-VWF decreased the secretion of normal VWF in a dose-dependent manner, the secreted VWF showing all the multimers. Two relatives of the propositus were single heterozygotes for the T1156M mutation and were either asymptomatic or had the manifestations of mild type 1 VWD. The expression data and studies of platelet VWF indicate that the T1156M mutation results in intracellular retention of VWF rather than impaired synthesis. Three other members of the family were heterozygotes for the Q2470X mutation and demonstrated the variable expressivity of a null allele.
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| 28. |
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| 29. |
- Lindahl, Tomas, et al.
(författare)
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INR calibration of Owren-type prothrombin time based on the relationship between PT% and INR utilizing normal plasma samples
- 2004
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 91:6, s. 1223-1231
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Tidskriftsartikel (refereegranskat)abstract
- Prothrombin time (PT) is clinically important and is used to monitor oral anticoagulant therapy. To obtain PT results in international normalized ratio (INR), the current standardization procedure is complex and involves reference reagents. The PT of diluted plasma samples can be determined with a combined thromboplastin (the Owren-type procedure), but not necessarily with a plain thromboplastin (the Quick-type procedure). Owren-type PT procedures can therefore, as an alternative to the INR calibration, be calibrated with diluted normal plasma to give PT results in percent of normal PT activity (PT%). The present study explored if a plasma-based calibration of an Owren-type PT procedure can be used to obtain results in INR. The approach was to establish a relationship between PT% and INR by multi-center analysis of 365 samples from healthy individuals and patients on warfarin treatment. INR values were obtained by manual Quick-type reference procedure and PT% values by various automated Owren-type procedures. A relationship INR = (I/PT% + 0.018)10.028 was found. A calibration procedure, based on the relationship, was investigated. Calibrators were the median PT of 21 normal plasma at dilutions representing 100%, 50%, 25%, 12.5% and 6.25% of normal PT activity. These were assigned INR values of 1.00, 1.36, 2.07, 3.05 and 6.36. Calibration of various Owren-type assays was repeatedly performed by 5 expert laboratories during 3 consecutive years. The INR values of certain lyophilised or frozen control plasmas were determined. The frozen control plasmas had externally assigned INR values according to WHO guidelines. Within the laboratory, CV was typically below 3%. No appreciable difference among the results of the different laboratories or the three assay occasions was found. Externally assigned and INR values were essentially identical to those found. These and other results indicated that the calibration procedure was reproducible, precise and accurate. Thus, an Owren-type PT assay can be calibrated with normal plasma samples to give results in INR and the investigated calibration procedure can be proposed for this purpose.
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| 30. |
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| 31. |
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| 32. |
- Look, M, et al.
(författare)
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Pooled analysis of prognostic impact of uPA and PAI-I in breast cancer patients
- 2003
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 90:3, s. 538-548
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Tidskriftsartikel (refereegranskat)abstract
- In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-I for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-I survival analyses, reflecting the interaction between nodal status and uPA/PAI-I. The estimates for uPA and PAI-I were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-I were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-I are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups.
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| 33. |
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| 34. |
- Malm, Karl, et al.
(författare)
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Prevention of thrombosis following deep arterial injury in rats by bovine activated protein C requiring co-administration of bovine protein S.
- 2003
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 90:2, s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- The antithrombotic effect of bovine activated protein C (bAPC) given with or without bovine protein S (bPS) was investigated in a rat model of deep arterial injury. A segment of the left common carotid artery was isolated between vascular clamps and opened longitudinally. An endarterectomy was performed and the arteriotomy was closed with a running suture, whereafter the vessel was reperfused by removing the clamps. The antithrombotic effect (vascular patency rates 31 minutes after reperfusion) and the arteriotomy bleeding were measured. Ten treatment groups each containing 10 rats and a control group of 20 animals were in a blind random fashion given intravenous bolus injections of increasing doses of activated protein C, with or without co-administration of protein S. The groups received either bAPC alone (0.8, 0.4, 0.2 or 0.1 mg/kg), bAPC (0.8, 0.4, 0.2, 0.1 or 0.05 mg/kg) combined with bPS (0.6 mg/kg), or bPS alone (0.6 mg/kg) whereas the control group received vehicle only. Administered alone, bAPC or bPS had no antithrombotic effect, regardless of dosage. In contrast, all groups that were treated with bAPC in combination with bPS demonstrated a significant antithrombotic effect, as compared to controls. Neither bAPC, bPS, nor the combination of bAPC and bPS increased the arteriotomy bleeding significantly compared to controls. In vitro clotting assays using bAPC or bPS alone yielded only minor prolongation of clotting time, where-as bAPC combined with bPS prolonged the clotting time con-siderably, demonstrating the dependence on the APC-cofactor activity of bPS for expression of anticoagulant activity by bAPC. In conclusion, our study shows the in vivo significance of protein S as a cofactor to activated protein C, and that potent antithrombotic effect can be achieved by low doses of bAPC combined with bPS, without producing hemorrhagic side effects.
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| 35. |
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| 36. |
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| 37. |
- Oldgren, Jonas, et al.
(författare)
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Myocardial damage, coagulation activity and the response to thrombin inhibition in unstable coronary artery disease.
- 2004
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 91:2, s. 381-7
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Tidskriftsartikel (refereegranskat)abstract
- Unstable coronary artery disease is in most cases associated with plaque rupture, activation of the coagulation system and subsequent intracoronary thrombus formation which may cause myocardial cell damage. The aim of the present analysis was to assess the relation between troponin T, markers of coagulation activity, i.e. prothrombin fragment 1+2, thrombin-antithrombin complex, soluble fibrin and D-dimer, and ischemic events, i.e. death, myocardial (re-)infarction or refractory angina. 320 patients with unstable coronary artery disease were randomized to 72 hours infusion with inogatran, a low molecular weight direct thrombin inhibitor, or unfractionated heparin. Patients with elevated troponin levels had higher levels of prothrombin fragment 1+2, soluble fibrin and D-dimer before, during, and at 24 hours after cessation of anticoagulant treatment. These troponin-positive patients tended to have worse short-term clinical outcome, without relation to markers of coagulation activity. Troponin-negative patients with unchanged or early increased thrombin generation during treatment had a cluster of ischemic events within 24 hours after cessation of the study drug. The 30-day ischemic event rate was 19 % in troponin-negative patients with unchanged or early increased prothrombin fragment 1+2, and 5.7 % in patients with decreased prothrombin fragment 1+2, p=0.006, and similarly 15 % in troponin-negative patients with unchanged or early increased thrombin-antithrombin complex and 4.5 % in patients with decreased thrombin-antithrombin complex, p=0.02. In conclusion, in unstable coronary artery disease a troponin elevation indicates higher risk and higher coagulation activity. However, among the troponin negative patients, with a lower risk and lower coagulation activity, a part of the patients seem to be non-responders to treatment with a thrombin inhibitor expressed as unchanged or raised coagulation activity and a raised risk of ischemic events early after cessation of treatment.
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| 38. |
- Osterlund, Barbro, et al.
(författare)
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Intracoronary beta2 receptor activation induces dynamic local t-PA release in the pig.
- 2003
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Ingår i: Thrombosis and haemostasis. - 0340-6245 .- 2567-689X. ; 90:5, s. 796-802
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Tidskriftsartikel (refereegranskat)abstract
- To investigate beta2 -adrenergic agonist-mediated effects on coronary fluxes of local fibrinolytic factors, healthy anaesthetised and instrumented pigs (n=10) were studied during infusion of isoprenaline (IPR) into the left main coronary artery. Coronary net fluxes of total t-PA antigen, active t-PA and total PAI-1 antigen were determined at baseline and at 3, 5, 7 and 10 minutes of IPR infusion. During IPR, net release of total t-PA increased in a biphasic pattern with transiently high levels at 3 (+440 %) and 7 minutes (+620%) and returned towards baseline at 10 minutes. Net coronary release of active t-PA increased with maximum levels at 3 minutes (+50%). Baseline coronary net flux of total PAI -1 showed a decrease which was most pronounced at 10 minutes. To conclude, a fast beta2 agonist-mediated local release of t-PA into the coronary vasculature was demonstrated. For total t-PA, this response was characterised by a biphasic release profile.
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| 39. |
- Persson, Kristina, et al.
(författare)
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Analytical considerations for free protein S assays in protein S deficiency
- 2001
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 86:5, s. 1144-1147
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Tidskriftsartikel (refereegranskat)abstract
- Protein S is an anticoagulant protein that circulates in plasma in complex with C4b-binding protein; (C4BP) or in free form. Deficiency of protein S increases the risk of venous thrombosis. Measurement of free protein S, as compared to total levels, has been shown to be superior for prediction of protein S deficiency. We studied the effects of different handling protocols for an immuno- and a ligand (C4BP)-based assay for free protein S. When the assay was performed at 37 degrees C, the levels of free protein S in plasma from protein S deficient patients were approximately twice those obtained at room temperature. The reason for this phenomenon was that plasmas from protein S deficient patients exhibited a time-, temperature-, and dilution-dependent increase in free protein S, which, was more pronounced than corresponding dilution of the normal plasma that was used to create the standard curve. These findings demonstrate the importance of assay procedure and sample handling in assays for free protein S.
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| 40. |
- Ramström, Sofia, 1973-, et al.
(författare)
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Platelet phosphatidylserine exposure and procoagulant activity in clotting whole blood : different effects of collagen,TRAP and calcium ionophore A23187
- 2003
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 89:1, s. 132-141
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the effects of different platelet agonists onphosphatidylserine (PS) exposure and clotting times in bloodwithout anticoagulants. Similar reductions in clotting time wereobtained for collagen, TRAP-6 or calcium ionophore A23187(50 µmol/L), in spite of huge differences in PS expression[6.7 ± 2.4%, 2.3 ± 0.5% and 99.9 ± 0.1%, respectively (mean ±SD, n = 5)]. Furthermore, the clotting times were much longerfor samples with A23187 exposing the same amounts of PS assamples with collagen or TRAP-6. Annexin V reversed theclotting time reduction, but could not prevent coagulation.Addition of phospholipid vesicles containing 20% PS neitheraffected the clotting times nor induced clotting in recalcified,platelet-free plasma.We conclude that platelet PS exposure is necessary, but notsufficient, for the coagulation amplification observed whenplatelets are stimulated via physiological receptors in a wholeblood environment.
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| 41. |
- Reiner, AP, et al.
(författare)
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Diabetes duration may modify the association between genetic variation in the glycoprotein la subunit of the platelet collagen receptor and risk of severe diabetic retinopathy: a working hypothesis
- 2003
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 89:1, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors appear to contribute to the severity and progression of diabetic retinopathy. We assessed the associations of the C807T and Glu505Lys variants of the glycoprotein Ia (alpha(2) integrin) subunit of the platelet/endothelial collagen receptor and risk of retinopathy in a population-based survey of 288 diabetic patients in one Swedish community. Neither variant was associated with retinopathy risk overall. However, the 807T variant was associated with increased risk of severe retinopathy, and the association was modified by diabetes duration. Among patients with diabetes of longer duration (greater than or equal to25 years), the 807T variant was strongly associated with risk of severe retinopathy (odds ratio 7.49, 95% confidence interval 1.75 to 32.1). There was no association between the 807T variant and risk of severe retinopathy among patients with diabetes duration <25 years. The Lys505 variant of glycoprotein la was associated with an odds ratio for severe retinopathy of 1.88 (95% confidence interval 0.83, to 4.24). Overall, there was a significant interaction between glycoprotein la genotype and duration of diabetes on the risk of retinopathy (P-value for interaction = 0.019). These results suggest the hypothesis that genetic variation of platelet glycoprotein la may play a particularly important role during the advanced stages of. diabetic retinopathy.
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| 42. |
- Rezende, SM, et al.
(författare)
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Genetic and phenotypic variability between families with hereditary protein S deficiency
- 2002
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 87:2, s. 258-265
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Tidskriftsartikel (refereegranskat)abstract
- While many mutations thought to result in protein S (PS) deficiency are known. there have been few attempts to relate genotype expression with plasma phenotype. We have investigated the nature and consequence of PS gene (PROS 1) mutations in 17 PS-deficient families who presented with mixed type I and type III phenotypes. Seven different mutations were found in nine families: delG-34 (STOP codon at -24), Val-24Glu, Arg49Cys. Asn217Ser, Gly295Val, +5 G to A intron j and His623Pro. PS wild type (PSWT) and the five missense mutants were transiently expressed in COS-1 cells. All mutants expressed lower (p<0.05) PS antigen compared to PSWT (100%). The mutants Val-24Glu, Gly295Val and His623Pro expressed very low/undetectable PS levels. The Mutant Asn217Ser produced around 30% of PSWT, while the mutant Arg49Cys had the highest PS levels (around 50%). Metabolic labelling and pulse-chase experiments showed that all of the mutants had impaired secretion, but this was of variable severity. Also, enhanced intracellular degradation of unsecreted material was found for all mutants. There was a strong correspondence between plasma free PS levels in carriers of the mutations. secreted PS from transfected COS-1 cells and labelled PS from 24 h conditioned medium in pulse-chase experiment. We conclude that the magnitude of secretion defect depends on the nature of the PROS1 mutation and influences the level of free PS in plasma. It is likely that the severity of the secretion defect will determine the risk for venous thrombosis.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
- Schulman, S, et al.
(författare)
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Pregnancy, heparin and osteoporosis
- 2002
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 87:2, s. 180-181
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Tidskriftsartikel (refereegranskat)
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| 47. |
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| 48. |
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| 49. |
- Serra, J, et al.
(författare)
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Multicentre evaluation of IL Test (TM) Free PS: A fully automated assay to quantify Free Protein S
- 2002
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 88:6, s. 975-983
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Tidskriftsartikel (refereegranskat)abstract
- Deficiency of the anticoagulant vitamin K-dependent protein S (PS) is associated with increased risk of venous thrombosis. In human plasma, PS circulates in two forms: as free protein (free PS) and PS bound to C4b-binding protein (C4BP), a regulator of the complement system. Assays for free PS have higher sensitivity and specificity for protein S deficiency than assays for total protein S. We have extensively evaluated the analytical performance of a novel assay for free PS, the IL Test(TM) Free Protein S, which takes advantage of the affinity of C4BP for free PS, and compared its performance to existing methods. IL Test(TM) Free Protein S is a rapid, fully automated turbidimetric assay consisting of two reagents: a C4BP coated latex and an anti-PS monoclonal antibody coated latex. The test range, precision and linearity were adequate and the assay tolerated high concentrations of interfering substances of clinical significance. The reference range agreed with previously published studies. The analysis of 903 patient samples belonging to 20 different clinical. categories with the new assay yielded free PS results that agreed well with those obtained using the assays established in the participating laboratories. The study demonstrated the IL Test(TM) Free Protein S to be rapid, reliable and easy to perform.
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| 50. |
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