| 1. |
- Bruzelius, Maria, et al.
(författare)
-
F11 is associated with recurrent VTE in women A prospective cohort study
- 2016
-
Ingår i: Thrombosis and Haemostasis. - : Schattauer Gmbh. - 0340-6245 .- 2567-689X. ; 115:2, s. 406-414
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95 % CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95 % CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95 % CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction.
|
|
| 2. |
- Bruzelius, Maria, et al.
(författare)
-
Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism
- 2014
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 134:2, s. 426-432
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case-control study (n = 2753) from Sweden. Materials and Methods: 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. Results: Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181). Conclusions: It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.
|
|
| 3. |
- Bruzelius, Maria, et al.
(författare)
-
PDGFB, a new candidate plasma biomarker for venous thromboembolism : results from the VEREMA affinity proteomics study
- 2016
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:23, s. E59-E66
-
Tidskriftsartikel (refereegranskat)abstract
- There is a clear clinical need for high-specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far, such markers have remained elusive. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish Venous Thromboembolism Biomarker Study, using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1), von Willebrand factor (VWF), glutathione peroxidase 3 (GPX3), and platelet-derived growth factor beta (PDGFB). For replication, we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. These results confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whereas only weak trends were observed for HIVEP1 and GPX3. Although plasma levels of VWF and PDGFB correlated modestly (rho similar to 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P = .002). PDGF. was verified as the target of the capture antibody by immunocapture mass spectrometry and sandwich enzyme-linked immunosorbent assay. In conclusion, we demonstrate that high-throughput affinity plasma proteomic profiling is a valuable research strategy to identify potential candidate biomarkers for thrombosis-related disorders, and our study suggests a novel association of PDGFB plasma levels with VTE.
|
|
| 4. |
- Majeed, Ammar, et al.
(författare)
-
Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates : a cohort study
- 2017
-
Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 130:15, s. 1706-1712
-
Tidskriftsartikel (refereegranskat)abstract
- There is uncertainty regarding the effectiveness and occurrence of thromboembolic events in patients treated with prothrombin complex concentrates (PCCs) for the management of major bleeding events (MBEs) onrivaroxabanor apixaban. We investigated the effectiveness of PCCs given for the management of MBEs in patients on rivaroxaban or apixaban. Between 1 January 2014 and 1 October 2016, we prospectively included patients on rivaroxaban or apixaban treated with PCCs for the management of MBEs. The effectiveness of PCCs was assessed by using the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria for the assessment of the effectiveness of major bleeding management. The safety outcomes were thromboembolic events and all-cause mortality with in 30 days after treatmentwith PCCs. Atotal of 84 patients received PCCs for the reversal of rivaroxaban or apixaban due to a MBE. PCCs were given at amedian (interquartile range) dose of 2000 IU (1500-2000 IU). Intracranial hemorrhage (ICH) was themost common site of bleeding requiring reversal (n = 5 59; 70.2%), followed by gastrointestinal bleeding in 13 (15.5%) patients. Management with PCCs was assessed as effective in 58 (69.1%) patients and ineffective in 26 (30.9%) patients. Most patients with ineffective hemostasis with PCCs had ICH (n 5 16; 61.5%). Two patients developed an ischemic stroke, occurring 5 and 10 days after treatment with PCC. Twenty seven (32%) patients died within 30 days after a MBE. The administration of PCCs for the management of MBEs associated with rivaroxaban or apixaban is effective inmost cases and is associated with a low risk of thromboembolism. Our findings are limited by the absence of a control group in the study.
|
|
| 5. |
|
|
| 6. |
- Bergek, Anna, 1973-, et al.
(författare)
-
Are patents with multiple inventors from different countries a good indicator of international R&D collaboration? The case of ABB
- 2010
-
Ingår i: Research Policy. - : Elsevier BV. - 0048-7333 .- 1873-7625. ; 39, s. 1321-1334
-
Tidskriftsartikel (refereegranskat)abstract
- Based on the critical case of ABB, this paper questions the relevance of using patents with multiple inventors from different countries (“cross-country patents”) as an indicator of international R&D collaboration. The study shows that less than half of ABB’s cross-country patents are the result of international R&D collaboration as described by one of the more inclusive definitions found in previous literature. Only a third of the patents are the result of joint R&D activities between different MNC subsidiaries or firms. We also discuss the implications of our study for the assignment of patents to countries based on inventor addresses.
|
|
| 7. |
|
|
| 8. |
- Bruzelius, Fredrik, et al.
(författare)
-
Test report
- 2010
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is the document summarising the testing experience and knowledge gained from the physical testing activities within the eVALUE project. The document contains brief introductions to the testing scenarios as well as short summaries of conclusions. Appended to this document are the testing reports that have been compiled during the different test sessions. Physical testing at test tracks all across Europe has been the main input in the development of scenarios and test procedures. This document describes the development tests that have been performed during 2010, based on a first draft set of testing protocols. The experience from the performed tests has been used as an important input to the revision of the testing protocols, i.e. the formal documents that describe how a test should be performed and evaluated. These protocols are documented in the separate Deliverable 3.2.
|
|
| 9. |
- Bruzelius, Maria
(författare)
-
Exploration of novel mechanisms and biomarkers for venous thromboembolism : a genetics and proteomics study
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Venous thromboembolism (VTE) contributes to a large health burden and incidence increases exponentially with age. ~25% patients will experience a recurrent event and there is a 2-fold risk for death in the following years. Risk prediction remains a challenge. Aims to: Investigate a presumed overlap between cardiovascular disease and VTE. Expand current knowledge of established pathways in VTE risk by combining clinical and genetic epidemiology. Apply affinity proteomics to identify novel plasma susceptibility biomarkers. Methods and results: 39 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) and 18 risk VTE-SNPs from candidate gene approach studies or genome-wide association studies (GWAS) were identified from a literature search. The SNPs were genotyped in 2,835 women from the ThromboEmbolism Hormone study (TEHS), a Swedish nationwide case-control study in women (2002-2009). Association was assessed with logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. The genetic predictors that contributed to first VTE were assessed in a cohort of 1010 women with VTE from TEHS, followed up until a recurrence, death or November 2011 (TEHS follow-up). The SNP r579459 in the ABO locus was the only CAD-SNP that was significant associated with VTE (OR 1.57 (95% CI: 1.39-1.78, p= 6.4 10-13)). Seven VTE risk-SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with 4 SNP-SNP interactions contributed to the genetic risk score for VTE with an AUC of 0.66 (95% CI: 0.64-0.68). After adding clinical risk factors the AUC attained 0.84 (95% CI: 0.82-0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. In TEHS follow-up study, the overall recurrence rate was 20 per 1000 person-years (95% CI; 16-24). Carriers of the risk alleles of F5 rs6025 (FVL) (HR=1.7 (95% CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95% CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at 5 years follow-up. Plasma samples from 88 VTE cases and 85 controls, part of the Venous thromboembolism Biomarker Study (VEBIOS), were screened against 408 candidate proteins targeted by 755 antibodies using multiplex bead arrays. Proteins that significantly associated with VTE after Bonferroni correction were tested for replication in plasma samples of 580 cases and 589 controls from the FARIVE study. In VEBIOS, plasma levels of four proteins, HIVEP1, VWF, GPX3 and PDGFB were significantly associated with VTE after Bonferroni correction. VWF and PDGFB successfully replicated in FARIVE with increased plasma levels in VTE cases compared to controls as initially observed in VEBIOS. Conclusion: ABO locus was the only shared genetic risk factor between CVD and VTE. A limited set of genetic predictors improved prediction of incident VTE in women at high risk. Our data indicated that interactions among SNPs increase the goodness of fit when predicting VTE. A combination of genotypes i.e. F11 rs2289252 and FVL, may be of potential clinical relevance for risk prediction for recurrence. Affinity plasma proteomics proved to be a valuable research strategy to discover novel biomarkers
|
|
| 10. |
|
|
