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Life
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The New Frontier of Venous Thromboembolism
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The New Frontier of Venous Thromboembolism

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 26908

Special Issue Editors

Dr. Giuseppe Camporese

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Guest Editor
Department of Internal Medicine, General Medicine Unit, Thrombotic and Haemorrhagic Disorders Unit, University Hospital of Padua, Padua, Italy
Interests: vascular medicine; cardiology; coagulation and thrombotic disorders
Special Issues, Collections and Topics in MDPI journals
Dr. Pierpaolo Di Micco

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Guest Editor
Department of Medicine, AFO Medicine Interna, PO Santa Maria delle Grazie Hospital, ASL Napoli 2 Nord, 80078 Napoli, Italy
Interests: immunology; vascular medicine; cardiology; infectious disease; neurology; coagulation and clinical laboratory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Venous thromboembolism (VTE) is a disorder that includes deep vein thrombosis and pulmonary embolism and is the third most common vascular event and a leading cause of death worldwide. In recent years, a great effort has been made to improve decision making in VTE patients’ care, and the last decade has seen major advances in the development and management of new antithrombotic drugs (e.g., DOACs and the current research on antisense oligonucleotides and factor XI inhibitors).The research in this field is quickly evolving with the main goal of achieving the greatest reduction in thrombotic risk, with the minimum risk of bleeding, both for VTE prevention and treatment. In the coming years, we will face some intriguing challenges concerning unresolved issues in the management of VTE. Namely, in the field of cancer-associated thrombosis (which patients cannot use DOACs? Should incidental VTE be treated similar to symptomatic VTE? Is it safe to give DOACs to patients with gastrointestinal or urogenital cancers? How about drug–drug interactions? Should all cancer patients receive thromboprophylaxis? Is arterial thrombosis a problem?), or in the field of the basic molecular research (with the goal of better understanding the mechanisms that differentiate clot formation occurring in the setting of hemostasis versus those that promote thrombosis, and the mechanisms that drive pathological thrombus formation), or in the field of research on defining treatment duration that extends beyond consideration of presenting characteristics (e.g., provoked vs. unprovoked VTE, distal vs. proximal DVT, incidental asymptomatic PE vs. symptomatic PE) and on the introduction of innovative imaging, biomarkers and treatments, or in the management of some groups of patients underrepresented in the registrative randomized clinical trials (e.g., patients with severe renal impairment or receiving hemodialysis, those at extremes of weight, those with reduced absorption because of gastrointestinal surgery, those with autoimmune diseases, and those who have had venous stenting procedures; pediatric or pregnant patients; patients with thrombosis in unusual sites; patient undergoing transplantation).

We warmly invite you and your colleagues to submit original research articles, reviews, systematic reviews, meta-analyses, brief reports, and case reports that address issues related to the future management of VTE risk factors, risk assessment, diagnosis, treatment, prognosis, follow-up, monitoring, and prevention. In particular, submissions with a particular focus on an innovative and comprehensive approach to the topic, or current unmet needs in antithrombotic strategies are particularly encouraged and appreciated.

Dr. Giuseppe Camporese
Dr. Pierpaolo Di Micco
Guest Editors

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. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • venous thromboembolism
  • treatment
  • prophylaxis
  • biomarkers
  • antithrombotic drugs

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

2 pages, 174 KiB  
Editorial
Editorial on the Special Issue “The New Frontier of Venous Thromboembolism”
by Pierpaolo Di Micco, Egidio Imbalzano and Giuseppe Camporese
Life 2023, 13(10), 2071; https://doi.org/10.3390/life13102071 - 17 Oct 2023
Viewed by 1051
Abstract
In recent years, great efforts have been made to improve decision making in caring for patients of venous thromboembolism (VTE) [...] Full article
(This article belongs to the Special Issue The New Frontier of Venous Thromboembolism)

Research

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13 pages, 1729 KiB  
Article
Central Venous Access and the Risk for Thromboembolic Events in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer
by Harriet Rydell, Ylva Huge, Victoria Eriksson, Markus Johansson, Farhood Alamdari, Johan Svensson, Firas Aljabery and Amir Sherif
Life 2022, 12(8), 1198; https://doi.org/10.3390/life12081198 - 6 Aug 2022
Cited by 4 | Viewed by 2349
Abstract
Thromboembolic events (TEE) are high-risk complications in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for urothelial muscle-invasive bladder cancer (MIBC). The purpose of the study was to investigate any differences in TEE-incidence, comparing peripherally inserted central catheter (PICC) versus a totally [...] Read more.
Thromboembolic events (TEE) are high-risk complications in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for urothelial muscle-invasive bladder cancer (MIBC). The purpose of the study was to investigate any differences in TEE-incidence, comparing peripherally inserted central catheter (PICC) versus a totally implanted port (PORT) as CVA (central venous access) during NAC. We identified 947 cystectomized MIBC-patients from four Swedish medical centers in 2009–2021. Inclusion criteria were cT2-T4aN0M0 and 375 patients were finally eligible and evaluated, divided into: NAC-administered (n = 283) resp. NAC-naïve-NAC-eligible (n = 92), the latter as tentative control group. Data on TEEs and types of CVA were retrospectively collected and individually validated, from final transurethral resection of the bladder tumor (TUR-B) to 30 days post-RC. Adjusted logistic regression and log rank test were used for statistical analyses. Amongst NAC-administered, 83% (n = 235) received PICCs and 15% (n = 42) PORTs. Preoperative TEEs occurred in 38 PICC-patients (16.2%) and in one PORT-patient (2.4%), with 47 individual events registered. We found a significantly increased odds ratio of TEE in NAC-administered PICC-patients compared to in PORT-patients (OR: 8.140, p-value: 0.042, 95% CI 1.078–61.455). Our findings indicate a greater risk for pre-RC TEEs with PICCs than with PORTs, suggesting favoring the usage of PORTs for MIBC-NAC-patients. Full article
(This article belongs to the Special Issue The New Frontier of Venous Thromboembolism)
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9 pages, 238 KiB  
Article
Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy
by Pierpaolo Di Micco, Vladimir Rosa Salazar, Carmen Fernandez Capitan, Francesco Dentali, Covadonga Gomez Cuervo, José Luis Fernández Reyes, Jose Antonio Porras, Angeles Fidalgo, Elvira Grandone, Manuel Lopez Meseguer, Manuel Monreal and the RIETE Investigators
Life 2022, 12(8), 1128; https://doi.org/10.3390/life12081128 - 27 Jul 2022
Cited by 3 | Viewed by 1841
Abstract
Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) [...] Read more.
Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy—1485 (58.6%); delayed start—808 (32.5%); low doses—143 (5.7%); both conditions—54 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p < 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97–170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25–6.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban. Full article
(This article belongs to the Special Issue The New Frontier of Venous Thromboembolism)
10 pages, 1333 KiB  
Article
Prothrombinase-Induced Clotting Time to Measure Drug Concentrations of Rivaroxaban, Apixaban, and Edoxaban in Clinical Practice: A Cross-Sectional Study
by Vepusha Sathanantham, Lorenzo Alberio, Cédric Bovet, Pierre Fontana, Bernhard Gerber, Lukas Graf, Adriana Mendez, Thomas C. Sauter, Adrian Schmidt, Jan-Dirk Studt, Walter A. Wuillemin and Michael Nagler
Life 2022, 12(7), 1027; https://doi.org/10.3390/life12071027 - 11 Jul 2022
Cited by 1 | Viewed by 2307
Abstract
Prothrombinase-induced clotting time (PiCT) is proposed as a rapid and inexpensive laboratory test to measure direct oral anticoagulant (DOAC) drug levels. In a prospective, multicenter cross-sectional study, including 851 patients, we aimed to study the accuracy of PiCT in determining rivaroxaban, apixaban, and [...] Read more.
Prothrombinase-induced clotting time (PiCT) is proposed as a rapid and inexpensive laboratory test to measure direct oral anticoagulant (DOAC) drug levels. In a prospective, multicenter cross-sectional study, including 851 patients, we aimed to study the accuracy of PiCT in determining rivaroxaban, apixaban, and edoxaban drug concentrations and assessed whether clinically relevant drug levels could be predicted correctly. Citrated plasma samples were collected, and the Pefakit® PiCT was utilized. Ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure drug concentrations. Cut-off levels were established using receiver-operating characteristics curves. We calculated sensitivities and specificities with respect to clinically relevant drug concentrations. Spearman’s correlation coefficient between PiCT and drug concentrations was 0.85 in the case of rivaroxaban (95% CI 0.82, 0.88), 0.66 for apixaban (95% CI 0.60, 0.71), and 0.78 for edoxaban (95% CI 0.65, 0.86). The sensitivity to detect clinically relevant drug concentrations was 85.1% in the case of 30 µg L−1 (95% CI 82.0, 87.7; specificity 77.9; 72.1, 82.7), 85.7% in the case of 50 µg L−1 (82.4, 88.4; specificity 77.3; 72.5, 81.5), and 85.1% in the case of 100 µg L−1 (80.9, 88.4; specificity 73.2%; 69.1, 76.9). In conclusion, the association of PiCT with DOAC concentrations was fair, and the majority of clinically relevant drug concentrations were correctly predicted. Full article
(This article belongs to the Special Issue The New Frontier of Venous Thromboembolism)
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Review

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13 pages, 1468 KiB  
Review
Catheter-Directed Interventions for the Treatment of Lower Extremity Deep Vein Thrombosis
by Kajol J. Shah and Trisha L. Roy
Life 2022, 12(12), 1984; https://doi.org/10.3390/life12121984 - 27 Nov 2022
Cited by 10 | Viewed by 7822
Abstract
Lower extremity deep vein thrombosis (DVT) leads to significant morbidity including pain, swelling, and difficulty walking in the affected limb. If left untreated, DVT increases the risk of pulmonary embolism (PE), recurrent venous thromboembolism (VTE), and post thrombotic syndrome (PTS). The objective of [...] Read more.
Lower extremity deep vein thrombosis (DVT) leads to significant morbidity including pain, swelling, and difficulty walking in the affected limb. If left untreated, DVT increases the risk of pulmonary embolism (PE), recurrent venous thromboembolism (VTE), and post thrombotic syndrome (PTS). The objective of this review was to identify catheter-directed interventions and their success rates for the treatment of lower extremity DVT. A comprehensive search of current and emerging catheter-directed interventions for lower extremity DVT treatment was conducted in PubMed and Google Scholar. Clinical trials, retrospective and prospective observational studies, and case reports were identified to classify percutaneous mechanical thrombectomy (PMT), catheter-directed thrombolysis (CDT), and pharmacomechanical CDT (PCDT) devices based on their mechanism of action and indication of use. Catheter-directed interventions such as PMT, CDT, and PCDT offer an alternative therapeutic strategy for DVT management, particularly in patients with limb-threatening conditions and absolute contraindications to anticoagulants. Currently, there are limited guidelines for the use of mechanical and pharmacomechanical devices because of the lack of clinical evidence available for their use in treatment. Future studies are required to determine the short and long-term effects of using catheter-directed interventions as well as their effectiveness in treating acute versus subacute and chronic DVT. Full article
(This article belongs to the Special Issue The New Frontier of Venous Thromboembolism)
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15 pages, 1098 KiB  
Review
Multidisciplinary Care for the Prevention and Treatment of Venous Thromboembolism in Patients with Cancer-Associated Thrombosis (CAT): Impact of Educational Interventions on CAT-Related Events and on Patients’ and Clinicians’ Awareness
by Beniamino Zalunardo, Chiara Panzavolta, Paola Bigolin and Adriana Visonà
Life 2022, 12(10), 1594; https://doi.org/10.3390/life12101594 - 13 Oct 2022
Cited by 5 | Viewed by 3159
Abstract
Cancer is a leading cause of death. Venous thromboembolism (VTE) is an often-overlooked cause of morbidity and mortality in cancer patients that can be readily prevented and treated. Actions are needed to reduce the morbidity and mortality of patients with cancer-associated thrombosis (CAT). [...] Read more.
Cancer is a leading cause of death. Venous thromboembolism (VTE) is an often-overlooked cause of morbidity and mortality in cancer patients that can be readily prevented and treated. Actions are needed to reduce the morbidity and mortality of patients with cancer-associated thrombosis (CAT). There is a need to increase awareness of the impact of CAT on cancer patients’ morbidity and mortality, on their quality of life and to understand the importance of more effective preventions and treatments of VTE in cancer patients. Moreover, it is of great importance to systematically assess the risk of VTE in regard to patients, cancer and treatment-related factors. Unfortunately, there are unmet clinical needs in the prevention and treatment of cancer-associated VTE. In this review, we discuss an action plan to ensure an increased awareness of and education on the issues that need to be addressed in order to improve the provision of appropriate prevention, early diagnosis and effective and safe treatment of VTE to all cancer patients and, ultimately, to reduce morbidity and mortality. Full article
(This article belongs to the Special Issue The New Frontier of Venous Thromboembolism)
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27 pages, 3464 KiB  
Review
Pathogenesis of Two Faces of DVT: New Identity of Venous Thromboembolism as Combined Micro-Macrothrombosis via Unifying Mechanism Based on “Two-Path Unifying Theory” of Hemostasis and “Two-Activation Theory of the Endothelium”
by Jae C. Chang
Life 2022, 12(2), 220; https://doi.org/10.3390/life12020220 - 31 Jan 2022
Cited by 8 | Viewed by 6517
Abstract
Venous thrombosis includes deep venous thrombosis (DVT), venous thromboembolism (VTE), venous microthrombosis and others. Still, the pathogenesis of each venous thrombosis is not clearly established. Currently, isolated distal DVT and multiple proximal/central DVT are considered to be the same macrothrombotic disease affecting the [...] Read more.
Venous thrombosis includes deep venous thrombosis (DVT), venous thromboembolism (VTE), venous microthrombosis and others. Still, the pathogenesis of each venous thrombosis is not clearly established. Currently, isolated distal DVT and multiple proximal/central DVT are considered to be the same macrothrombotic disease affecting the venous system but with varying degree of clinical expression related to its localization and severity. The genesis of two phenotypes of DVT differing in clinical features and prognostic outcome can be identified by their unique hemostatic mechanisms. Two recently proposed hemostatic theories in vivo have clearly defined the character between “microthrombi” and “macrothrombus” in the vascular system. Phenotypic expression of thrombosis depends upon two major variables: (1) depth of vascular wall damage and (2) extent of the injury affecting the vascular tree system. Vascular wall injury limited to endothelial cells (ECs) in sepsis produces “disseminated” microthrombi, but intravascular injury due to trauma extending from ECs to subendothelial tissue (SET) produces “local” macrothrombus. Pathogen-induced sepsis activates the complement system leading to generalized endotheliopathy, which releases ultra large von Willebrand factor (ULVWF) multimers from ECs and promotes ULVWF path of hemostasis. In the venous system, the activated ULVWF path initiates microthrombogenesis to form platelet-ULVWF complexes, which become “microthrombi strings” that produce venous endotheliopathy-associated vascular microthrombotic disease (vEA-VMTD) and immune thrombocytopenic purpura (ITP)-like syndrome. In the arterial system, endotheliopathy produces arterial EA-VMTD (aEA-VMTD) with “life-threatening” thrombotic thrombocytopenic purpura (TTP)-like syndrome. Typically, vEA-VMTD is “silent” unless complicated by additional local venous vascular injury. A local venous vessel trauma without sepsis produces localized macrothrombosis due to activated ULVWF and tissue factor (TF) paths from damaged ECs and SET, which causes distal DVT with good prognosis. However, if a septic patient with “silent” vEA-VMTD is complicated by additional vascular injury from in-hospital vascular accesses, “venous combined micro-macrothrombosis” may develop as VTE via the unifying mechanism of the “two-path unifying theory” of hemostasis. This paradigm shifting pathogenetic difference between distal DVT and proximal/central DVT calls for a reassessment of current therapeutic approaches. Full article
(This article belongs to the Special Issue The New Frontier of Venous Thromboembolism)
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