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- Colic, J, et al.
(författare)
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ALTERED FIBRIN CLOT PROPERTIES IN PATIENTS WITH SYSTEMIC SCLEROSIS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 695-696
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Vasculopathy in Systemic sclerosis (SSc) is connected with the activation of coagulation. However, the fibrinolytic activity still remains unclear since the most preliminary evidences are discordant (1, 2).Objectives:To assess the haemostatic function, fibrin clot density and clot lysis time in SSc patients and healthy controls (HC) to determine their relation to disease findings.Methods:Patients who fulfilled the 2013 ACR/EULAR SSc criteria and have never been treated with endothelin receptor antagonist, phosphodiesterase 5 inhibitors or prostanoids were eligibile. Our study included 58 SSc patients [36 limited (lcSSc) and 22 diffuse cutaneous SSc (dcSSc)] and 46 sex/age-matched HC. Clinical evaluation of patients was performed, including high-resolution CT (HRCT), pulmonary function tests and the revised EUSTAR activity index. The interstitial lung disease (ILD) group (n = 15) was defined as moderate or severe changes on HRCT, with a forced vital capacity (FVC) < 85% predicted, without evidence of significant pulmonary arterial hypertension. The serum concentration of ICAM1 and von Willebrand factor antigen (VWF) were measured by ELISA. Haemostatic potential parameters; including overall haemostasis (OHP), overall coagulation (OCP) and overall fibrinolysis (OFP) potential, were assessed and endogenous thrombin potential (ETP) was determined. Maximum absorbance (Cmax), reflects the fibrin clot density and clot lysis time (Lys50t0), reflects fibrinolytic susceptibility, were calculated from OHP and OCP curves (3). Fibrin structure was visualised using scanning electron microscopy (SEM).Results:The OFP value was significantly decreased, Lys50t0 prolonged (p<0.05), while OHP and ETP were increased (p<0.05) in patients. In dSSc group ETP, OHP, Cmax and Lys50t0 were higher compared to HC (p<0.05). In SSc group, a positive association was found between coagulation parameters (OCP, OHP, Cmax) and the erythrocyte sedimentation rate (ESR), fibrinogen and ICAM1 (respectively p<0.05). Lys50t0 was positively correlated with ICAM1, ESR and VWF (respectively p<0.001, p<0.05, p<0.05). An inverse correlation was found between Cmax and both the diffusing capacity of the lungs for carbon monoxide (r=-0.408, p<0.01) and FVC (r=-0.318, p<0.01). Increased Cmax was found in ILD respect to HC (p<0.01). Denser plasma clot was associated with active disease (p<0.01). Longer Lys50t0 was observed in pitting scars group (p<0.01). Prolonged Lys50t0 was independently predicted by ICAM1 (OR 1.12, 95% CI 1.03–1.2, p<0.01).Conclusion:Our results provide evidences of denser plasma fibrin clot among patients with lung involvement and impaired fibrinolysis, selectively presented among SSc patients with piting scars. Thus, these patients might be at risk for thrombotic complications. Raised ICAM-1 levels could reflect impaired fibrinolysis, giving insight the important role of this molecule in endothelial homeostasis.References:[1]Cerinic MM, et al. Blood coagulation, fibrinolysis, and markers of endothelial dysfunction in systemic sclerosis. Semin Arthritis Rheum. 2003;32:285–95[2]Lippi G, et al. Plasma D-dimer concentration in patients with systemic sclerosis.Thromb J. 2006;4:2.[3]Carter AM, et al. Heritability of clot formation, morphology, and lysis: the EuroCLOT study. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2783-9Figure 1.SEM images of fibrin network in 1 representative sample from a SSc (A) and 1from HC sample (B).Disclosure of Interests:Jelena Colic: None declared, Aleksandra Antovic: None declared, Iva Pruner: None declared, Jelena Vojinovic Consultant of: Roche, Abbvie, Pfizer, MSD, Speakers bureau: Roche, Abbvie, Pfizer, MSD, Mirjana Sefik Bukilica: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche
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- Colic, J, et al.
(författare)
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CLOT LYSIS TIME PREDICTS RECURRENT DIGITAL ULCERS IN SYSTEMIC SCLEROSIS AFTER ONE YEAR OF FOLLOW-UP: A NESTED CASE-CONTROL STUDY
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 693-693
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Digital ulcers (DU) are a common visible manifestation of vasculopathy in systemic sclerosis (SSc), which could be recurrent and associated with disability and mortality (1). Although vasculopathy is connected with impaired coagulation/fibrinolysis system and aberrant expression of adhesion molecules, there are few data about their role in developing recurrent DU.Objectives:To evaluate the possible role of Fibrin generation/Fibrinolysis parameters and adhesion molecules in the prediction of new ischaemic DU oncet during a 1-year follow-up and their impact on the time to new DU onset (TD).Methods:From 58 consecutive patients with SSc who fulfilled the 2013 ACR/EULAR SSc criteria and have never been treated with endothelin receptor antagonist, phosphodiesterase 5 inhibitors or prostanoids, a total of 38 patients with ever had DU, either active at inclusion or in past, were enrolled in a prospective cohort study. Each patient was given a “DU diary”. Demografic, clinical and serologycal data were recorded. The serum concentration of ICAM1 and E selectin were measured by ELISA. Haemostatic potential parameters: overall haemostasis (OHP), overall coagulation (OCP) and overall fibrinolysis (OFP) potential were assessed. Maximum absorbance (Cmax), reflects the fibrin clot density and clot lysis time (Lys50t0, time from initiation of clot formation to the time at which a 50% fall in absorbance from Cmax in the lysis assay), reflects fibrinolytic susceptibility, were calculated (2). Fibrin structure was visualised using scanning electron microscopy (SEM).Results:Over the follow-up period,18 patients (45.5%) developed new DU with the average TD of 7.4±2.9 months. There was no differance in ASA and CCB treatment among two groups (p>0.05). The OFP value was significantly decreased (p<0.01), Lys50t0 prolonged (p<0.05), while OHP was increased (p<0.05) in patients experienced new DU. Lys50t0 showed good validity in identifying patients with new DU oncet (AUC 0.683 95% CI 0.5 - 0.9). By multivariate analysis including clinical data in model the Lys50t0 (HR 1.2, 95% CI 1.1-1.3, p=0.018) and active DU at enrollment (HR 9.6, 95% CI 1.4-66.8, p=0.022) were identified as independent risk factors for the occurrence of new DU. TD was inversly correlated with ICAM1(p<0.001), E selectin (p<0.05), Cmax (p <0.05) and Lys50t0 (p<0.001). Model explaining 81.6% of the TD variability included Lys50t0 (β=- 0.55,p=0.003), E selectin (β=- 0.44,p=0.014) and fibrinogen (β=- 0.49,p=0.017). SEM revealed denser fibrin clots with thinner fibres in group experienced new DU compared to clots formed in plasma of patient without DU.Conclusion:Our results provide evidence that impaired fibrinolysis has critical role in the progression of microvascular disease, identifing clot lysis time as a strong predictor in the oncet of new digital ulcers in Systemic sclerosis. The higher level of E selectin and the longer lysis time are, the shorter is time until the onset of new digital ulcer. These results could be used in selection of patients at high risk of developing recurrent digital ulcer and therefore allow earlier therapeutic intervention.References:[1]Allanore Y, Distler O, Matucci-Cerinic M, Denton CP. Review: Defining a Unified Vascular Phenotype in Systemic Sclerosis. Arthritis Rheumatol. 2018 Feb;70(2):162-170[2]Carter AM, et al. Heritability of clot formation, morphology, and lysis: the EuroCLOT study. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2783-9.Figure 1.SEM images of fibrin network in 1 representative sample from a SSc patient with (A) and 1from patient without (B) new DU oncetDisclosure of Interests:None declared
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- Colic, J, et al.
(författare)
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EXTRACELLULAR VESICLES AS POTENTIAL BIOMARKERS OF EARLY DISEASE STAGE IN SYSTEMIC SCLEROSIS
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 761-761
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Extracellular vesicles (EVs) are membrane-coated vesicles most often generated from the vasculature and circulating blood cells upon cell activation and during the early phase of apoptosis (1).ObjectivesTo evaluate the concentration of different subpopulations of EVs in plasma from patients with SSc in relation to the disease duration and to the markers of endothelial injury.MethodsOur study included 59 SSc patients (36 limited (lSSc) and 23 diffuse cutaneous subset (dSSc)) and 46 healthy age and gender matched controls subjects. Disease duration less than 3 years in patients with dSSc and less than 5 years in those with lSSc was considered as early disease stage. Clinical evaluation of patients was performed. EVs were analysed with flow cytometry after staining platelet poor plasma with fluorescent cell-specific monoclonal antibodies. The concentration of following phosphatidylserine-positive EVs (PS+ EVs) were analyzed: total EVs, endothelial EVs (EEVs; CD144+), platelet EVs (PEVs; CD42b+), monocytes EVs (LEVs; CD14+), EVs expressing ICAM1 (CD54+), VCAM1 (CD106+) and P selectin (CD62p+). Serum levels of ICAM1, VCAM1 and P selectin were determined with ELISA.ResultsMedian disease duration of our cohort was 4 (0-29) years (early lSSc [20/36]: 2.5 (0-4.5) years; early dSSc [11/23]: 10 (1-30) months). All types of investigated EVs were significantly elevated in SSc patients compared to controls (p<0.05). Patients with early disease stage had significantly increased levels of all PS+EVs compared to HC (p<0.05). Moreover, the levels of EVs expressing ICAM1 and VCAM1 showed good validity in identifying patients with early disease stage (AUC 0.7, p<0.01). PEVs were increased in early dSSc compared to early lSSc, but the difference did not reach statistical significance (p=0.07). There was a correlation between serum levels and the levels of EVs expressing specific adhesion molecules (ICAM1: r=0.7, p<0.01; VCAM1: r=0.7, p<0.01; P selectin: r=-0.7, p<0.01), only within the group with early dSSc subtype of the disease. Further correlations were detected between ICAM1+EVs with either mRSS (r=0.07, p< 0.01) or EUSTAR activity index (r=0.07, p= 0.02) among patients with early dSSc.ConclusionIncreased levels of circulating EVs of different cell origin were present in patients with early SSc. EVs expressing either ICAM1 or VCAM1 could be novel biomarkers of early disease. EVs expressing ICAM1 showed association with severity of skin involvement and disease activity in patients with early dSSc giving insight into their role in the pathogenesis of SSc.References[1]J Colic, M Matucci-Cerinic, S Guiducci and N Damjanov. Review: Microparticles in systemic sclerosis, targets or tools to control fibrosis: This is the question!. Journal of Scleroderma and Related Disorders. 2019; 5(34):239719831985735Disclosure of InterestsNone declared
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| 6. |
- Colic, J, et al.
(författare)
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Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis
- 2022
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 49:6, s. 598-606
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Tidskriftsartikel (refereegranskat)abstract
- To assess thrombin generation, fibrin formation, and structure together with the fibrinolytic status in patients with systemic sclerosis (SSc) in relation to the occurrence of digital ulcers (DUs) during the course of disease.Methods.We studied variables of endothelial dysfunction, thrombin generation, overall hemostatic potential, and fibrin clot turbidity in plasma from 58 patients with SSc (39 with DU history and 19 DU-naïve) and 46 matched healthy controls (HCs). Fibrin structure was visualized using scanning electron microscopy (SEM). Finally, 39 patients with a history of DUs were followed for 1.5 years and the predictive value of all investigated markers for new DU onset was explored.Results.Significantly enhanced endogenous thrombin potential (ETP) and prolonged clot lysis time (CLT) were found in patients with DUs compared to HCs. CLT was prolonged in patients with DUs compared to those without, showing good validity in identifying DUs with an area under the curve of 0.7 (95% CI 0.6–0.8). The levels of ETP and intercellular adhesion molecule 1 were independently associated with CLT. Over the follow-up period, 20 patients developed new DUs. CLT was prolonged (P < 0.001) in patients with new DU episodes, especially those with recurrent DUs. Regression analysis showed that the Raynaud phenomenon visual analog scale and CLT were predictors of new DUs (OR 1.1, 95% CI 1.0–1.1 and OR 1.2, 95% CI 1.1–1.3, respectively). SEM confirmed denser fibrin clots in patients with new DUs.Conclusion.Our results suggest that impaired fibrinolysis might have an emerging role in underlying digital vasculopathy and its progression in SSc.
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