| 1. |
- Almskog, LM, et al.
(författare)
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Rotational thromboelastometry results are associated with care level in COVID-19
- 2021
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Ingår i: Journal of thrombosis and thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 51:42, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- High prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The primary aim of this study was to test whether rotational thromboelastometry (ROTEM) at admission indicates hypercoagulopathy and predicts the disease severity, assessed as care level, in COVID-19 patients. The study was designed as a prospective, observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: (1) regular wards or (2) wards with specialized ventilation support. Conventional coagulation tests, blood type and ROTEM were taken at admission. 60 patients were included; age 61 (median), 67% men, many with comorbidities (e.g. hypertension, diabetes). The ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with in healthy controls (p < 0.001) and higher in severely ill patients compared with in patients at regular wards (p < 0.05). Our results suggest that hypercoagulopathy is present early in patients with mild to moderate disease, and more pronounced in severe COVID-19 pneumonia. Non-O blood types were not overrepresented in COVID-19 positive patients. ROTEM variables showed hypercoagulopathy at admission and this pattern was more pronounced in patients with increased disease severity. If this feature is to be used to predict the risk of thromboembolic complications further studies are warranted.
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| 2. |
- Danin-Mankowitz, H, et al.
(författare)
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The risk of venous thromboembolism and physical activity level, especially high level: a systematic review
- 2021
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Ingår i: Journal of thrombosis and thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 52:2, s. 508-516
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is the third most common cause of cardiovascular disease. Connection between high level of physical activity (PA) and the onset of VTE is unknown. We searched the literature on the possible association between PA level, especially high levels, and the risk of VTE. A systematic review was carried out to identify relevant articles on the relation between PA level and VTE. The initial search was conducted together with the Karolinska Institutet University Library in February 2018, with follow-up searches after that. In total, 4383 records were found and then screened for exclusion of duplicates and articles outside the area of interest. In total, 16 articles with data on 3 or more levels of PA were included. Of these, 12 were cohort and 4 were case-control studies. Totally 13 studies aimed at investigating VTE cases primarily, while three studies had other primary outcomes. Of the 16 studies, five found a U-shaped association between PA level and VTE risk, although non-significant in three of them. Two articles described an association between a more intense physical activity and a higher risk of VTE, which was significant in one. Nine studies found associations between increasing PA levels and a decreasing VTE risk. Available literature provides diverging results as to the association between high levels of PA and the risk of venous thromboembolism, but with several studies showing an association. Further research is warranted to clarify the relationship between high level PA and VTE.
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| 3. |
- Nymberg, Peter, et al.
(författare)
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Mitochondria-DNA copy-number and incident venous thromboembolism among middle-aged women : a population-based cohort study
- 2021
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 52:1, s. 148-157
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is the third most common cardiovascular disease. Low amount of mitochondrial DNA copy number (mtDNA-CN) has been associated with arterial cardiovascular disease (CVD) and reflects mitochondrial dysfunctions. However, whether mtDNA-CN is associated with VTE has not been determined. To examine the association between mtDNA-CN and incident VTE among middle-aged women. 6917 women aged 50-64 years, followed for 20 years in the Women's Health In the Lund Area (WHILA) study. DNA samples for mtDNA quantification were available from 2521 women. Quantification of mtDNA-CN was performed using a well-optimized droplet digital PCR method. After exclusions of women with anticoagulant treatment, women living in nursing homes, and women who were diagnosed with cancer, stroke, VTE, or coronary heart disease at baseline, a cohort of 2117 women remained for analysis. Cox regression was used to analyze the relationship between mtDNA-CN and time to VTE (hazard ratio = HR). In total, 87 women were diagnosed with VTE during follow-up, corresponding to an incidence rate of 2.8 per 1000 person-years. Neither crude nor adjusted HR for mtDNA-CN were significantly associated with incident VTE. A sensitivity analysis with inclusion of excluded women did not change the results. MtDNA-CN was not significantly associated with VTE. The present study suggests that mtDNA-CN, reflecting mitochondrial dysfunction, should not be considered a biomarker that plays a major role for developing VTE. However, due to limited study size we may not exclude minor associations.
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| 4. |
- Nymberg, Peter, et al.
(författare)
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Self-rated health and venous thromboembolism among middle-aged women : a population-based cohort study
- 2020
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 49:3, s. 344-351
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is one of the most common types of cardiovascular diseases (CVDs) and is associated with increased mortality-risk. Poor-self rated health (SHR) has been associated with elevated inflammatory markers and CVDs. However, little is known about as a predictor of incident VTE. To examine the association between self-rated health, lifestyle and incident VTE among middle-aged women. 6917 women aged 50–64 years, followed for 20 years in the Women’s Health In the Lund Area (WHILA) study. After exclusion of those who medicated with anticoagulants, were living in nursing homes or suffered from cancer, stroke, VTE or CHD before baseline, a cohort of 5626 women remained. Cox regression was used to analyse the relationship between self-rated health and time to VTE, censored for any of the previous mentioned diseases during follow-up. Data were collected by questionnaires, physical examinations and Swedish registers. In total, 220 women were affected by VTE corresponding to an incidence rate of 3.9 per 1000 person-years. Adjustment for self-rated health did not significantly predict incident VTE, and neither did any of the lifestyle-related habits (e.g. physical activity and dietary habits including alcohol consumption), besides smoking. This study supports previous results with varicose veins and waist circumference as strong predictors of VTE. Poor self-rated health does not seem to be a valid predictor of VTE. Among lifestyle-related parameters, smoking was significantly associated with risk of VTE. We could also confirm the effect of the other already known risk factors.
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| 5. |
- Paar, V, et al.
(författare)
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Anti-coagulation for COVID-19 treatment: both anti-thrombotic and anti-inflammatory?
- 2021
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Ingår i: Journal of thrombosis and thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 51:21, s. 226-231
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been linked to a higher risk of mortality compared to influenza, which is mainly due to severe secondary diseases, such as acute respiratory distress syndrome (ARDS). In turn, ARDS is characterized by an acute inflammation and an excessive activity of the coagulation cascade, rising the vulnerability for venous thromboembolic events. In order to investigate the relation of inflammation and the influence of coagulation factors on their release, human peripheral mononuclear blood cells (PBMCs) were treated with autologous serum, heparinized plasma and different doses of fibrin. Thereafter, the concentration of pro-inflammatory cytokines and chemokines in the secretome of PBMCs was measured by enzyme-linked immunosorbent assay. Our analyses revealed autologous serum to significantly increase the secretion of cytokines and chemokines after 24 h of incubation time. Furthermore, the addition of fibrin markedly increased the secretion of cytokines and chemokines by PBMCs in a dose-dependent manner. Consequently, in accordance with previous studies, our study outlines that anti-coagulation may constitute a promising tool for the treatment of SARS-CoV-2, reducing both, the cytokine storm, as well as the risk for thrombotic complications.
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| 6. |
- Rossi, R., et al.
(författare)
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The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome
- 2021
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 51:2, s. 545-551
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Tidskriftsartikel (refereegranskat)abstract
- Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H-1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.
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| 7. |
- Wange, Niklas, et al.
(författare)
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Bleeding risk in patients with venous thromboembolic events treated with new oral anticoagulants
- 2021
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer. - 0929-5305 .- 1573-742X. ; 52:1, s. 315-323
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Tidskriftsartikel (refereegranskat)abstract
- New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.
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| 8. |
- Tanhaian, Abbas, et al.
(författare)
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In Silico and In Vitro Investigation of a Likely Pathway for Anti-Cancerous Effect of Thrombocidin-1 as a Novel Anticancer Peptide
- 2020
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Ingår i: Protein peptide letters. - : Bentham Science Publishers Ltd. - 0929-8665 .- 1875-5305. ; 27:8, s. 751-762
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antimicrobial and antifungal activities of Thrombocidin-1 (TC-1) is shown previously, however, the anti-cancerous feature of this peptide is still uncovered. Objective: The objective is to evaluate anti-cancerous feature of recombinant TC-1. Methods: In this study, based on the significant similarity of rTC-1 and IL-8 in case of coding sequence, tertiary structure, and also docking and molecular dynamic simulation (MD) results with CXCR1, a receptor which has positive correlation with different cancers, a likely pathway for anti-cancerous effect of rTC-1 was proposed. In addition, the coding sequence of TC-1+6 x histidine (rTC-1) was inserted into the pET22b(+) vector and cloned and expressed by E. coli BL21 and finally purified through nickel affinity column. Afterward, the retrieved rTC-1 was used in MTT assay against mouse colon adenocarcinoma, hepatocellular carcinoma, chondrosarcoma, mouse melanoma, and breast adenocarcinoma cell lines to investigate its probable anticancer application. Results: Docking and MD simulation results showed that rTC-1 and IL-8 share almost the same residues in the interaction with CXCR1 receptor. Besides, the stability of the rTC-l_CXCR1(1-)(38) complex was shown during 100ns MD simulation. In addition, the successful expression and purification of rTC-1 depict an 8kD peptide. The IC50 results of MTT assay revealed that rTC-1 has cytotoxic effect on C26-A and SW1353 cancerous cell lines. Conclusion: Therefore, apart from probable anti-cancerous effect of rTC-1 on C26-A and SW1353 cell lines, this peptide may be able to mimic the anti-cancerous pathway of IL-8.
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