Ultrastructure and composition of thrombi in coronary and peripheral artery disease: Correlations with clinical and laboratory findings

Kovács, András; Sótonyi, Péter; Nagy, Anikó Ilona; Tenekedjiev, Kiril; Wohner, Nikolett; Komorowicz, Erzsébet; Kovács, Eszter; Nikolova, Natalia; Szabó, László; Kovalszky, Ilona; Machovich, Raymund; Szelid, Zsolt; Becker, David J.; Merkely, Béla; Kolev, Krasimir

doi:10.1016/j.thromres.2015.02.004

Cited by 17 publications

(22 citation statements)

References 19 publications

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“…Regression analysis and statistical hypothesis testing were performed on an array of thrombus composition and routine clinical data of each patient. Previously described algorithms were used (Kuiper statistical test for equality of distribution [28], one-tail statistical test for median equality [25], linear regression models with response variable described as quadratic function of one or two explanatory variables [25]) with modifications detailed in the Online Resource.…”

Section: Methodsmentioning

confidence: 99%

“…In the case of CAD and PAD patients thrombi were collected during acute therapeutic catheter interventions and operations, as previously described [1]. In AIS, thrombi were removed via stent-retriever thrombectomy from acutely occluded large vessels of the circle of Willis.…”

Section: Thrombus Collectionmentioning

confidence: 99%

“…Cardiovascular disorders remain the leading cause of death worldwide, coronary artery disease (CAD) and acute ischemic stroke (AIS) representing the two medical conditions with the strongest impact on mortality and disability [1]. The prevalence of peripheral artery disease (PAD) has also increased in the past years [2], thus contributing to the growing disease burden of arterial thrombotic disorders.…”

Section: Introductionmentioning

confidence: 99%

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Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases

Farkas

Szabó

et al. 2019

Thrombosis Research

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Highlights-Neutrophil extracellular traps (NETs) modify the structure and stability of fibrin.-NET content of thrombi varies at different locations (brain, heart, peripheral arteries).-DNA and histones in thrombi correlate with age and systemic inflammatory markers.-The amount of fibrin is similar at all examined arterial locations.-Thicker fibrin fibers are formed in coronaries than in brain and peripheral arteries. 3 Abstract Introduction-The ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizations and their interrelations with routinely available clinical data. Patients and methods-Thrombi extracted from AIS (n=78), CAD (n=66) or PAD (n=64) patients were processed for scanning electron microscopy, (immune)stained for fibrin, citrullinated histone H3 (cH3) and extracellular DNA. Fibrin fiber diameter, cellular components, DNA and cH3 were measured and analyzed in relation to clinical parameters. Results-DNA was least present in AIS thrombi showing a 2.5-fold lower DNA/fibrin ratio than PAD, whereas cH3 antigen was unvaryingly present at all locations. The NET content of thrombi correlated parabolically with systemic inflammatory markers and positively with patients' age. The median platelet content was lower in PAD (2.2%) than in either AIS (3.9%) or CAD (3.1%) and thrombi from smokers contained less platelets than non-smokers. Fibrin fibers were significantly thicker in male patients with CAD (median fiber diameter 76.3 nm) compared to AIS (64.1 nm) or PAD (62.1 nm) and their diameter correlated parabolically with systemic inflammatory markers.Conclusions-The observed NET-related variations in thrombus structure shed light on novel determinants of thrombus stability that eventually affect both the spontaneous progress and therapeutic outcome of ischemic arterial diseases.

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Section: Methodsmentioning

confidence: 99%

Section: Thrombus Collectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases

Farkas

Szabó

et al. 2019

Thrombosis Research

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“…The electron microscopic measurements generate data on fibrin fiber diameter and thrombus occupancy by fibrin and blood cells (red blood cells, leukocytes and platelets). The immunehistochemical measurements generate data on the ratio of fibrin and platelet antigens 27 . The data is analysed using hypothesis testing for differences between groups of patients with common clinical features in order to draw general conclusions on the characteristics of the disease.…”

Section: Incorporating Fuzzy Sets In Statistical Problems With Non-fumentioning

confidence: 99%

“…For example, red blood cells are known to modify the fibrin structure causing formation of thinner fibers 28 . The red blood cell occupancy in different sections of the same thrombus can vary between 7% and 21% 27 . If these are considered as separate observations, this artificially increases the number of clots with thin or with thick fibers taken into consideration.…”

Section: Incorporating Fuzzy Sets In Statistical Problems With Non-fumentioning

confidence: 99%

Bootstrap Kuiper Testing of the Identity of 1D Continuous Distributions using Fuzzy Samples

Nikolova¹,

Chai²,

Ivanova³

et al. 2015

IJCIS

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This paper aims to statistically test the null hypothesis H 0 for identity of the probability distribution of onedimensional (1D) continuous parameters in two different populations, presented by fuzzy samples of i.i.d. observations. A degree of membership to the corresponding population is assigned to any of the observations in the fuzzy sample. The test statistic is the Kuiper's statistic, which measures the identity between the two sample cumulative distribution functions (CDF) of the parameter. A Bootstrap algorithm is developed for simulation-based approximation for the CDF of the Kuiper statistic, provided that H 0 is true. The p value of the statistical test is derived using the constructed conditional distribution of the test statistic. The main idea of the proposed Bootstrap test is that, if H 0 is true, then the two available fuzzy samples can be merged into a unified fuzzy sample. The latter is summarized into a conditional sample distribution of the 1D continuous parameter used for generation of synthetic pairs of fuzzy samples in different pseudo realities. The proposed algorithm has four modifications, which differ by the method to generate the synthetic fuzzy sample and by the type of the conditional sample distribution derived from the unified fuzzy sample used in the generation process. Initial numerical experiments are presented which tend to claim that the four modifications produce similar results.

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Oxidative Stress as a Thrombophilic Factor in Behçet Syndrome

et al. 2019

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Ultrastructure and composition of thrombi in coronary and peripheral artery disease: Correlations with clinical and laboratory findings

Cited by 17 publications

References 19 publications

Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases

Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases

Bootstrap Kuiper Testing of the Identity of 1D Continuous Distributions using Fuzzy Samples

Oxidative Stress as a Thrombophilic Factor in Behçet Syndrome

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