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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 37417

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Dr. Isabella Russo

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Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole, 10, Orbassano, I-10043 Turin, Italy
Interests: platelets function; nitric oxide; haemostasis; thrombosis; anti-platelet drugs; platelet dysfunction in metabolic diseases
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Special Issue Information

Dear Colleagues,

Thrombosis occurs when a thrombus forms inside blood vessels disrupting blood flow. It represents a major complication of cardio- and cerebrovascular events, such as myocardial infarction, acute ischemic stroke, or venous thromboembolism.

The components of thrombi include fibrin, red blood cells, platelets, leukocytes, and neutrophil extracellular traps, and this heterogeneous composition is extensively influenced by the specific location in which it develops and by disease etiopathogenesis.

Furthermore, there is an increasing interest in the extracellular vesicles released by numerous cells through membrane shedding that can contribute to transferring biological messages at a lengthy distance from the triggering event and used as biomarkers of thrombo-embolic pathology.

Considering the high prevalence of the thrombotic scenarios associated with metabolic and atherosclerotic diseases, the aim of the current Special Issue is to disseminate the latest scientific achievements in the field of biological and molecular mechanisms involved in impaired coagulation, platelet reactivity, and/or fibrinolysis.

Manuscripts should be related to the following areas of interest:

Explanation of thrombosis pathogenetic mechanisms;
Searching for new biomarkers for the detection of prothrombotic risk;
The use of new research techniques in thrombus studies.

Both original and review articles providing new insights into the subject are invited for submission.

Dr. Isabella Russo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

thrombosis
platelets
coagulation
diabetes
obesity
insulin resistance
metabolic disease
cardiovascular diseases

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Published Papers (9 papers)

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Research

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13 pages, 2779 KiB

Open AccessArticle

PECAM-1/Thrombus Ratio Correlates with Blood Loss during Off-Pump Coronary Artery Bypass Grafting (OPCAB) Surgery: A Preliminary Study

by Natalia Bielicka, Adrian Stankiewicz, Tomasz Misztal, Szymon Kocańda, Ewa Chabielska and Anna Gromotowicz-Popławska

Int. J. Mol. Sci. 2023, 24(17), 13254; https://doi.org/10.3390/ijms241713254 - 26 Aug 2023

Cited by 1 | Viewed by 1085

Abstract

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is considered an antiplatelet molecule. Previously, we introduced a new parameter called the PECAM-1/thrombus ratio, which indicates the proportion of PECAM-1 in the thrombus and provides a precise description of human platelet activity (in vitro). The aim of this study was to determine whether the PECAM-1/thrombus ratio could serve as a predictive factor for bleeding events during off-pump coronary artery bypass grafting (OPCAB). To achieve this, we collected blood samples from 20 patients scheduled to undergo OPCAB surgery. We assessed the PECAM-1/thrombus ratio by evaluating thrombus formation on collagen fibers under flow conditions. Subsequently, we compared the ability of the PECAM-1/thrombus ratio in predicting bleeding risk with other methods that evaluate hemostasis activity. These methods included assessing platelet P-selectin secretion, platelet exposure of phosphatidylserine, plasma coagulation and fibrinolysis system activity, and thrombus formation using the T-TAS assay. Our findings revealed a positive correlation between the PECAM-1/thrombus ratio and the amount of blood component units transfused (BCUT) during the OPCAB surgery. Furthermore, BCUT did not show any significant correlation with other measured hemostasis parameters. This preliminary study suggests that the PECAM-1/thrombus ratio might be a good predictor of bleeding risk during the OPCAB procedure. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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11 pages, 1848 KiB

Open AccessArticle

Plasma Antithrombin III Levels Can Be a Prognostic Factor in Liver Cirrhosis Patients with Portal Vein Thrombosis

by Tsuyoshi Suda, Hajime Takatori, Takehiro Hayashi, Kiichiro Kaji, Kouki Nio, Takeshi Terashima, Tetsuro Shimakami, Kuniaki Arai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Kenichiro Okumura, Kazuto Kozaka and Taro Yamashita

Int. J. Mol. Sci. 2023, 24(9), 7732; https://doi.org/10.3390/ijms24097732 - 23 Apr 2023

Cited by 4 | Viewed by 1886

Abstract

Liver function influences the plasma antithrombin (AT)-III levels. AT-III is beneficial for patients with portal vein thrombosis (PVT) and low plasma AT-III levels. However, whether these levels affect prognosis in patients with cirrhosis-associated PVT remains unknown. This retrospective study involved 75 patients with cirrhosis and PVT treated with danaparoid sodium with or without AT-III. The plasma AT-III level was significantly lower in patients with liver failure-related death than in those with hepatocellular carcinoma (HCC)-related death (p = 0.005), although the Child–Pugh and albumin-bilirubin (ALBI) scores were not significantly different between these two groups. Receiver operating characteristic curve analysis of the plasma AT-III levels showed cutoff values of 54.0% at 5-year survival. Low plasma AT-III levels (<54.0%) were associated with significantly worse prognosis than high levels in both overall survival (p = 0.0013) and survival excluding HCC-related death (p < 0.0001). Low plasma AT-III (<54.0%) was also associated with a significantly worse prognosis among patients with Child–Pugh A/B or ALBI grade 1/2 (p < 0.0001). Multivariate analyses indicated that low plasma AT-III levels (<54.0%) were an independent prognostic factor for poor survival outcome. Low plasma AT-III levels may be associated with mortality, particularly liver failure-related death, independent of liver function. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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Review

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35 pages, 8343 KiB

Open AccessReview

Coronary Artery Spasm-Related Heart Failure Syndrome: Literature Review

by Ming-Jui Hung, Chi-Tai Yeh, Nicholas G. Kounis, Ioanna Koniari, Patrick Hu and Ming-Yow Hung

Int. J. Mol. Sci. 2023, 24(8), 7530; https://doi.org/10.3390/ijms24087530 - 19 Apr 2023

Cited by 6 | Viewed by 3403

Abstract

Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden’s angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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16 pages, 1814 KiB

Open AccessReview

Challenges of Anticoagulant Therapy in Atrial Fibrillation—Focus on Gastrointestinal Bleeding

by Alina Scridon and Alkora Ioana Balan

Int. J. Mol. Sci. 2023, 24(8), 6879; https://doi.org/10.3390/ijms24086879 - 7 Apr 2023

Cited by 6 | Viewed by 2727

Abstract

The rising prevalence and the complexity of atrial fibrillation (AF) pose major clinical challenges. Stroke prevention is accompanied by non-negligible risks, making anticoagulant treatment an ongoing challenge for the clinician. Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in most AF patients, mainly due to the ease of their use. However, assessing the bleeding risk in patients receiving oral anticoagulants remains—particularly in the case of DOACs—highly challenging. Using dose-adjusted warfarin increases threefold the risk of gastrointestinal bleeding (GIB). Although the overall bleeding risk appears to be lower, the use of DOACs has been associated with an increased risk of GIB compared to warfarin. Accurate bleeding (including GIB-specific) risk scores specific for DOACs remain to be developed. Until then, the assessment of bleeding risk factors remains the only available tool, although the extent to which each of these factors contributes to the risk of bleeding is unknown. In this paper, we aim to provide a comprehensive review of the bleeding risk associated with oral anticoagulant therapy in AF patients, with a highlight on the latest insights into GIB associated with oral anticoagulation; we emphasize questions that remain to be answered; and we identify hotspots for future research. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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16 pages, 1122 KiB

Open AccessReview

Platelets and Cardioprotection: The Role of Nitric Oxide and Carbon Oxide

by Isabella Russo, Cristina Barale, Elena Melchionda, Claudia Penna and Pasquale Pagliaro

Int. J. Mol. Sci. 2023, 24(7), 6107; https://doi.org/10.3390/ijms24076107 - 24 Mar 2023

Cited by 10 | Viewed by 3474

Abstract

Nitric oxide (NO) and carbon monoxide (CO) represent a pair of biologically active gases with an increasingly well-defined range of effects on circulating platelets. These gases interact with platelets and cells in the vessels and heart and exert fundamentally similar biological effects, albeit through different mechanisms and with some peculiarity. Within the cardiovascular system, for example, the gases are predominantly vasodilators and exert antiaggregatory effects, and are protective against damage in myocardial ischemia-reperfusion injury. Indeed, NO is an important vasodilator acting on vascular smooth muscle and is able to inhibit platelet activation. NO reacts with superoxide anion (O₂(⁻•)) to form peroxynitrite (ONOO(⁻)), a nitrosating agent capable of inducing oxidative/nitrative signaling and stress both at cardiovascular, platelet, and plasma levels. CO reduces platelet reactivity, therefore it is an anticoagulant, but it also has some cardioprotective and procoagulant properties. This review article summarizes current knowledge on the platelets and roles of gas mediators (NO, and CO) in cardioprotection. In particular, we aim to examine the link and interactions between platelets, NO, and CO and cardioprotective pathways. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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24 pages, 1558 KiB

Open AccessReview

A Comprehensive Review of Risk Factors for Venous Thromboembolism: From Epidemiology to Pathophysiology

by Daniele Pastori, Vito Maria Cormaci, Silvia Marucci, Giovanni Franchino, Francesco Del Sole, Alessandro Capozza, Alessia Fallarino, Chiara Corso, Emanuele Valeriani, Danilo Menichelli and Pasquale Pignatelli

Int. J. Mol. Sci. 2023, 24(4), 3169; https://doi.org/10.3390/ijms24043169 - 5 Feb 2023

Cited by 79 | Viewed by 14858

Abstract

Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1–2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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25 pages, 9463 KiB

Open AccessReview

Finding the Needle in the Haystack: Serological and Urinary Biomarkers in Behçet’s Disease: A Systematic Review

by Marta Arbrile, Massimo Radin, Davide Medica, Paolo Miraglia, Letizia Rilat, Irene Cecchi, Silvia Grazietta Foddai, Alice Barinotti, Elisa Menegatti, Dario Roccatello and Savino Sciascia

Int. J. Mol. Sci. 2023, 24(3), 3041; https://doi.org/10.3390/ijms24033041 - 3 Feb 2023

Cited by 2 | Viewed by 2535

Abstract

Urinary and serological markers play an essential role in the diagnostic process of autoimmune diseases. However, to date, specific and reliable biomarkers for diagnosing Behçet’s disease (BD) are still lacking, negatively affecting the management of these patients. To analyze the currently available literature on serological and urinary BD biomarkers investigated in the last 25 years, we performed a systematic literature review using the Population, Intervention, Comparison, and Outcomes (PICO) strategy. One hundred eleven studies met the eligibility criteria (6301 BD patients, 5163 controls). Most of them were retrospective, while five (5%) were prospective. One hundred ten studies (99%) investigated serological biomarkers and only two (2%) focused on urinary biomarkers. One hundred three studies (93%) explored the diagnostic potential of the biomolecules, whereas sixty-two (56%) tested their effect on disease activity monitoring. Most articles reported an increase in inflammatory markers and pro-oxidant molecules, with a decrease in antioxidants. Promising results have been shown by the omics sciences, offering a more holistic approach. Despite the vast number of investigated markers, existing evidence indicates a persistent gap in BD diagnostic/prognostic indices. While new steps have been taken in the direction of pathogenesis and disease monitoring, international efforts for the search of a diagnostic marker for BD are still needed. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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21 pages, 2167 KiB

Open AccessReview

Thrombosis Models: An Overview of Common In Vivo and In Vitro Models of Thrombosis

by Sana Ayyoub, Ramon Orriols, Eduardo Oliver and Olga Tura Ceide

Int. J. Mol. Sci. 2023, 24(3), 2569; https://doi.org/10.3390/ijms24032569 - 29 Jan 2023

Cited by 10 | Viewed by 5327

Abstract

Occlusions in the blood vessels caused by blood clots, referred to as thrombosis, and the subsequent outcomes are leading causes of morbidity and mortality worldwide. In vitro and in vivo models of thrombosis have advanced our understanding of the complex pathways involved in its development and allowed the evaluation of different therapeutic approaches for its management. This review summarizes different commonly used approaches to induce thrombosis in vivo and in vitro, without detailing the protocols for each technique or the mechanism of thrombus development. For ease of flow, a schematic illustration of the models mentioned in the review is shown below. Considering the number of available approaches, we emphasize the importance of standardizing thrombosis models in research per study aim and application, as different pathophysiological mechanisms are involved in each model, and they exert varying responses to the same carried tests. For the time being, the selection of the appropriate model depends on several factors, including the available settings and research facilities, the aim of the research and its application, and the researchers’ experience and ability to perform surgical interventions if needed. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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Other

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12 pages, 3371 KiB

Open AccessCase Report

Integrated Approach to Highlighting the Molecular Bases of a Deep Vein Thrombosis Event in an Elite Basketball Athlete

by Cristina Mennitti, Ciro Miele, Carmela Scarano, Iolanda Veneruso, Alessandro Gentile, Rosaria Mormile, Francesca Saviano, Giovanni D’Alicandro, Cristina Mazzaccara, Giulia Frisso, Filomena Capasso, Valeria D’Argenio and Olga Scudiero

Int. J. Mol. Sci. 2023, 24(15), 12256; https://doi.org/10.3390/ijms241512256 - 31 Jul 2023

Viewed by 1281

Abstract

Acute or intense exercise can result in metabolic imbalances, muscle injuries, or reveal hidden disorders. Laboratory medicine in sports is playing an increasingly crucial role in monitoring athletes’ health conditions. In this study, we designed an integrated approach to explore the causes of a deep venous thrombosis event in an elite basketball player. Since the complete blood count revealed a marked platelet count (838 × 10³ µL), and thrombophilia screening tests did not reveal any significant alteration, we evaluated the thrombin generation, which highlights a state of hypercoagulability. First-level haemostasis exams showed only a slight prolongation of the activated Partial Thromboplastin Time (aPTT). Thus, screening tests for von Willebrand Disease showed a reduction in vWF parameters. Therefore, we directed our hypothesis towards a diagnosis of acquired von Willebrand disease secondary to Essential Thrombocythemia (ET). To confirm this hypothesis and highlight the molecular mechanism underlying the observed phenotype, molecular tests were performed to evaluate the presence of the most common mutations associated with ET, revealing a 52-bp deletion in the coding region of CALR exon 9. This case report highlights the importance of an integrated approach to monitoring the athletes’ health status to personalise training and treatments, thus avoiding the appearance of diseases and injuries that, if underestimated, can undermine the athlete’s life. Full article

(This article belongs to the Special Issue New Advances in Thrombosis)

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