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Management of Venous and Arterial Thrombosis
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Management of Venous and Arterial Thrombosis

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Vascular Medicine".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 48140

Special Issue Editors

Dr. Lucia Stančiaková

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Guest Editor
Department of Hematology and Blood Transfusion, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
Interests: inherited and acquired thrombophilia; genetics of thrombophilic states; hemostasis in vascular disorders (preeclampsia, arterial hypertension, diabetes mellitus); monitoring of the effectiveness of direct oral anticoagulants; hemostasis and genetics in high-risk pregnancy; monitoring of dual antiplatelet treatment; hemostasis and oncological diseases; thrombotic complications in bleeding disorders
Prof. Dr. Maha Othman

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Guest Editor
School of Medicine, Department of Biomedical and Molecular Sciences, Queen´s University, Kingston, ON, Canada
Interests: molecular genetics, diagnosis and management of platelet type on willebrand disease; the role of platelet GPIb alpha protein in hemostasis and beyond; hemostasis testing using thromboelastography (TEG) in pregnancy/placenta mediated complications, hormonal contraception and cancer associated thrombosis
Prof. Dr. Peter Kubisz

E-Mail Website
Guest Editor
Department of Hematology and Blood Transfusion, National Centre of Hemostasis and Thrombosis, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
Interests: inherited and acquired thrombophilia; physiology and pathophysiology of platelets; sticky platelet syndrome; genetic polymorphisms in disorders of hemostasis; endothelial and platelet dysfunction; hemostasis and cellular therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thrombosis is a basis for development of the three most serious cardiovascular-related causes of death—venous thromboembolism, myocardial infarction and ischemic stroke. Thrombi may be formed in any vein or artery; therefore, it is treated either by anticoagulant or antiplatelet agents.  Currently, with research advancements in the field of antithrombotic drugs, we have several possibilities for monitoring their effectiveness: prothrombin time measurement in the case of warfarin use, activated partial thromboplastin time for the titration of unfractionated heparin dose, and anti-IIa and anti-Xa activity tests for monitoring the levels of direct oral anticoagulants (DOACs), with anti-Xa activity also being implemented for low-molecular-weight heparins and fondaparinux. Patients who have to use DOACs do not need routine monitoring of their effectiveness. This testing is only required in specific clinical situations—for instance, before urgent surgical or other invasive procedures, in patients with traumatic injuries, extreme body mass index including pregnancy, acute progression of liver or renal failure, or on suspicion of non-compliance and overdose. Similarly, due to the cumulative evidence of stent thrombosis developing despite dual antiplatelet therapy, the demand for monitoring of such treatment is growing, especially in the era of the COVID-19 pandemic.

The present Special Issue aims to describe the pathophysiology, possibilities of clinical manifestation, diagnostic and treatment challenges of this life-threatening clinical condition. The authors would also like to sincerely dedicate this issue to all those who have died due to complications related to thrombosis.

Dr. Lucia Stančiaková
Prof. Dr. Maha Othman
Prof. Dr. Peter Kubisz
Guest Editors

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Keywords

  • thrombosis
  • hemostasis
  • management
  • antithrombotic therapy
  • monitoring
  • pathophysiology

Published Papers (19 papers)

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Research

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11 pages, 864 KiB  
Article
The Influence of Hyperthyroidism on the Coagulation and on the Risk of Thrombosis
by Nebojsa Antonijevic, Dragan Matic, Biljana Beleslin, Danijela Mikovic, Zaklina Lekovic, Marija Marjanovic, Ana Uscumlic, Ljubica Birovljev and Branko Jakovljevic
J. Clin. Med. 2024, 13(6), 1756; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm13061756 - 19 Mar 2024
Viewed by 521
Abstract
Introduction: Apart from the well-known fact that hyperthyroidism induces multiple prothrombotic disorders, there is no consensus in clinical practice as to the impact of hyperthyroidism on the risk of thrombosis. The aim of this study was to examine the various hemostatic and [...] Read more.
Introduction: Apart from the well-known fact that hyperthyroidism induces multiple prothrombotic disorders, there is no consensus in clinical practice as to the impact of hyperthyroidism on the risk of thrombosis. The aim of this study was to examine the various hemostatic and immunologic parameters in patients with hyperthyroidism. Methods: Our study consists of a total of 200 patients comprised of 64 hyperthyroid patients, 68 hypothyroid patients, and 68 euthyroid controls. Patient thyroid status was determined with standard tests. Detailed hemostatic parameters and cardiolipin antibodies of each patient were determined. Results: The values of factor VIII (FVIII), the Von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and anticardiolipin antibodies of the IgM class were significantly higher in the hyperthyroid patients than in the hypothyroid patients and euthyroid controls. The rate of thromboembolic manifestations was much higher in hyperthyroid patients (6.25%) than in hypo-thyroid patients (2.9%) and euthyroid controls (1.4%). Among hyperthyroid patients with an FVIII value of ≥1.50 U/mL, thrombosis was recorded in 8.3%, while in hyperthyroid patients with FVIII value ≤ 1.50 U/mL the occurrence of thrombosis was not recorded. The incidence of atrial fibrillation (AF) was significantly higher (8.3%) in the hyperthyroid patients compared to the hypothyroid patients (1.5%) and euthyroid controls (0%). Conclusions: High levels of FVIII, vWF, fibrinogen, PAI-1, and anticardiolipin antibodies along with other hemostatic factors contribute to the presence of a hypercoaguable state in patients with hyperthyroidism. The risk of occurrence of thrombotic complications is especially pronounced in patients with a level of FVIII exceeding 150% and positive anticardiolipin antibodies of the IgM class. Patients with AF are at particularly high risk of thrombotic complications due to a hyperthyroid prothrombotic milieu. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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19 pages, 1176 KiB  
Article
DNA Polymorphisms in Pregnant Women with Sticky Platelet Syndrome
by Lucia Stančiaková, Jana Žolková, Ľubica Vadelová, Andrea Hornáková, Zuzana Kolková, Martin Vážan, Miroslava Dobrotová, Pavol Hollý, Zuzana Jedináková, Marián Grendár, Tomáš Bolek, Matej Samoš, Kamil Biringer, Ján Danko, Tatiana Burjanivová, Zora Lasabová, Peter Kubisz and Ján Staško
J. Clin. Med. 2022, 11(21), 6532; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11216532 - 03 Nov 2022
Viewed by 1372
Abstract
Sticky platelet syndrome (SPS) is a thrombophilia caused by the increased aggregability of platelets in response to the addition of low concentrations of epinephrine (EPI) and/or adenosine diphosphate (ADP). Some of the single nucleotide polymorphisms (SNP), alleles and haplotypes of platelet glycoprotein receptors [...] Read more.
Sticky platelet syndrome (SPS) is a thrombophilia caused by the increased aggregability of platelets in response to the addition of low concentrations of epinephrine (EPI) and/or adenosine diphosphate (ADP). Some of the single nucleotide polymorphisms (SNP), alleles and haplotypes of platelet glycoprotein receptors were proved to have a role in the etiology of thrombotic episodes When comparing SPS and the control group, in VEGFA rs3025039, the p value for both CC vs. TT and CT vs. TT analyses was <0.001. Interestingly, no minor TT genotype was present in the SPS group, suggesting the thrombotic pathogenesis of recurrent spontaneous abortions (RSA) in these patients. Moreover, we found a significant difference in the presence of AT containing a risky A allele and TT genotype of ALPP rs13026692 (p = 0.034) in SPS patients when compared with the controls. Additionally, we detected a decreased frequency of the GG (CC) genotype of FOXP3 rs3761548 in patients with SPS and RSA when compared with the control group (p value for the CC (GG) vs. AA (TT) 0.021). This might indicate an evolutionary protective mechanism of the A (T) allele in the SPS group against thrombotic complications in pregnancy. These results can be used for antithrombotic management in such pregnant patients. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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16 pages, 3465 KiB  
Article
Exploring the Complex Network of Heme-Triggered Effects on the Blood Coagulation System
by Sarah Mubeen, Daniel Domingo-Fernández, Sara Díaz del Ser, Dhwani M. Solanki, Alpha T. Kodamullil, Martin Hofmann-Apitius, Marie-T. Hopp and Diana Imhof
J. Clin. Med. 2022, 11(19), 5975; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11195975 - 10 Oct 2022
Cited by 3 | Viewed by 2073
Abstract
Excess labile heme, occurring under hemolytic conditions, displays a versatile modulator in the blood coagulation system. As such, heme provokes prothrombotic states, either by binding to plasma proteins or through interaction with participating cell types. However, despite several independent reports on these effects, [...] Read more.
Excess labile heme, occurring under hemolytic conditions, displays a versatile modulator in the blood coagulation system. As such, heme provokes prothrombotic states, either by binding to plasma proteins or through interaction with participating cell types. However, despite several independent reports on these effects, apparently contradictory observations and significant knowledge gaps characterize this relationship, which hampers a complete understanding of heme-driven coagulopathies and the development of suitable and specific treatment options. Thus, the computational exploration of the complex network of heme-triggered effects in the blood coagulation system is presented herein. Combining hemostasis- and heme-specific terminology, the knowledge available thus far was curated and modeled in a mechanistic interactome. Further, these data were incorporated in the earlier established heme knowledge graph, “HemeKG”, to better comprehend the knowledge surrounding heme biology. Finally, a pathway enrichment analysis of these data provided deep insights into so far unknown links and novel experimental targets within the blood coagulation cascade and platelet activation pathways for further investigation of the prothrombotic nature of heme. In summary, this study allows, for the first time, a detailed network analysis of the effects of heme in the blood coagulation system. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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11 pages, 1438 KiB  
Article
Assessment of the Effect on Thromboprophylaxis with Multifaceted Quality Improvement Intervention based on Clinical Decision Support System in Hospitalized Patients: A Pilot Study
by Qian Gao, Kaiyuan Zhen, Lei Xia, Wei Wang, Yaping Xu, Chaozeng Si, Zhu Zhang, Fen Dong, Jieping Lei, Peiran Yang, Jixiang Liu, Ziyi Sun, Tieshan Zhang, Jun Wan, Wanmu Xie, Peng Liu, Cunbo Jia, Zhenguo Zhai and Chen Wang
J. Clin. Med. 2022, 11(17), 4997; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11174997 - 25 Aug 2022
Cited by 4 | Viewed by 2009
Abstract
Background: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. Methods: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, [...] Read more.
Background: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. Methods: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, orthopedic, and general surgery wards. Patients aged ≥18 years, without VTE in admission, were allocated to the intervention group and received regular care combined with multifaceted quality improvement intervention based on CDSS during hospitalization. VTE prophylaxis rate and the occurrence of hospital-associated VTE events were analyzed as primary and secondary outcomes. Results: A total of 3644 eligible residents were enrolled in this trial. With the implementation of the multifaceted quality improvement intervention based on the CDSS, the VTE prophylaxis rate of the intervention group increased from 22.93% to 34.56% (p < 0.001), and the incidence of HA-VTE events increased from 0.49% to 1.00% (p = 0.366). In the nonintervention group, the VTE prophylaxis rate increased from 24.49% to 27.90% (p = 0.091), and the incidence of HA-VTE events increased from 0.47% to 2.02% (p = 0.001). Conclusions: Multifaceted quality improvement intervention based on the CDSS strategy is feasible and expected to facilitate implementation of the recommended VTE prophylaxis strategies and reduce the incidence of HA-VTE in hospital. However, it is necessary to conduct more multicenter clinical trials in the future to provide more reliable real-world evidence. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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12 pages, 1409 KiB  
Article
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL): A Novel Biomarker for Prognostic Assessment and Risk Stratification of Acute Pulmonary Embolism
by Haixu Yu, Wei Rong, Jie Yang, Jie Lu, Ke Ma, Zhuohui Liu, Hui Yuan, Lei Xu, Yulin Li, Zhi-Cheng Jing and Jie Du
J. Clin. Med. 2022, 11(13), 3908; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11133908 - 05 Jul 2022
Viewed by 1633
Abstract
Background: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is associated with poor prognosis in cardiovascular diseases. However, the predictive value of TRAIL for the short-term outcome and risk stratification of acute pulmonary embolism (PE) remains unknown. Methods: This study prospectively included 151 normotensive [...] Read more.
Background: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is associated with poor prognosis in cardiovascular diseases. However, the predictive value of TRAIL for the short-term outcome and risk stratification of acute pulmonary embolism (PE) remains unknown. Methods: This study prospectively included 151 normotensive patients with acute PE. The study outcome was a composite of 30-day adverse events, defined as PE-related death, shock, mechanical ventilation, cardiopulmonary resuscitation, and major bleeding. Results: Overall, nine of 151 (6.0%) patients experienced 30-day adverse composite events. Multivariable logistic regression showed that TRAIL was an independent predictor of study outcome (OR 0.19 per SD; 95% CI 0.04–0.90). An ROC curve revealed that TRAIL’s area under the curve (AUC) was 0.83 (95% CI 0.76–0.88). The optimal cut-off value for TRAIL was 18 pg/mL, with a sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, and negative likelihood ratio of 89%, 69%, 99%, 15%, 2.87, and 0.16, respectively. Compared with the risk stratification algorithm outlined in the 2019 ESC guidelines, our biomarker-based risk stratification strategy (combining TRAIL and hs-cTnI) has a similar risk classification effect. Conclusion: Reduced plasma TRAIL levels predict short-term adverse events in normotensive patients with acute PE. The combination of the 2019 ESC algorithm and TRAIL aids risk stratification in normotensive patients with acute PE. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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14 pages, 2099 KiB  
Article
Characteristics and Outcomes of Patients Consulted by a Multidisciplinary Pulmonary Embolism Response Team: 5-Year Experience
by Arkadiusz Pietrasik, Aleksandra Gąsecka, Paweł Kurzyna, Katarzyna Wrona, Szymon Darocha, Marta Banaszkiewicz, Dariusz Zieliński, Dominika Zajkowska, Julia Maria Smyk, Dominika Rymaszewska, Karolina Jasińska, Marcin Wasilewski, Rafał Wolański, Grzegorz Procyk, Piotr Szwed, Michał Florczyk, Krzysztof Wróbel, Marcin Grabowski, Adam Torbicki and Marcin Kurzyna
J. Clin. Med. 2022, 11(13), 3812; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11133812 - 30 Jun 2022
Cited by 6 | Viewed by 2075
Abstract
(1) Background: Pulmonary embolism (PE) is the third most frequent acute cardiovascular condition worldwide. PE response teams (PERTs) have been created to facilitate treatment implementation in PE patients. Here, we report on the 5-year experience of PERT operating in Warsaw, Poland, with regard [...] Read more.
(1) Background: Pulmonary embolism (PE) is the third most frequent acute cardiovascular condition worldwide. PE response teams (PERTs) have been created to facilitate treatment implementation in PE patients. Here, we report on the 5-year experience of PERT operating in Warsaw, Poland, with regard to the characteristics and outcomes of the consulted patients. (2) Methods: Patients diagnosed with PE between September 2017 and December 2021 were included in the study. Clinical and treatment data were obtained from medical records. Patient outcomes were assessed in-hospital, at a 1- and 12-month follow-up. (3) Results: There were 235 PERT activations. The risk of early mortality was low in 51 patients (21.8%), intermediate–low in 83 (35.3%), intermediate–high in 80 (34.0%) and high in 21 (8.9%) patients. Anticoagulation alone was the most frequently administered treatment in all patient subgroups (altogether 84.7%). Systemic thrombolysis (47.6%) and interventional therapy (52%) were the prevailing treatment options in high-risk patients. The in-hospital mortality was 6.4%. The adverse events during 1-year follow-up included five deaths, two recurrent VTE and two minor bleeding events. (4) Conclusions: Our initial 5-year experience showed that the activity of the local PERT facilitated patient-tailored decision making and the access to advanced therapies, with subsequent low overall mortality and treatment complication rates, confirming the benefits of PERT implementation. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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11 pages, 1173 KiB  
Article
The Ottawa Score Performs Poorly to Identify Cancer Patients at High Risk of Recurrent Venous Thromboembolism: Insights from the TROPIQUE Study and Updated Meta-Analysis
by Corinne Frere, Benjamin Crichi, Clémentine Wahl, Elodie Lesteven, Jérôme Connault, Cécile Durant, Jose Antonio Rueda-Camino, Alexandra Yannoutos, Okba Bensaoula, Christine Le Maignan, Zora Marjanovic and Dominique Farge
J. Clin. Med. 2022, 11(13), 3729; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11133729 - 28 Jun 2022
Cited by 1 | Viewed by 1867
Abstract
The Ottawa score (OS) for predicting the risk of recurrent venous thromboembolism (VTE) in cancer patients with VTE may help to guide anticoagulant treatment decisions that will optimize benefit-risk ratios. However, data on its reliability are conflicting. We applied the OS to all [...] Read more.
The Ottawa score (OS) for predicting the risk of recurrent venous thromboembolism (VTE) in cancer patients with VTE may help to guide anticoagulant treatment decisions that will optimize benefit-risk ratios. However, data on its reliability are conflicting. We applied the OS to all cancer patients with VTE enrolled in the prospective multicenter TROPIQUE study who received low-molecular-weight heparin over a 6-month period. Of 409 patients, 171 (41.8%) had a high-risk OS. The 6-month cumulative incidence of recurrent VTE was 7.8% (95%CI 4.2–14.8) in the high-risk OS group versus 4.8% (95%CI 2.6–8.9) in the low-risk OS group (SHR 1.47; 95%CI 0.24–8.55). The Area Under the Receiver Operating Characteristic curve (AUROC) of the OS in identifying patients who developed recurrent VTE was 0.53 (95%CI 0.38–0.65), and its accuracy was 57.9%. Among individual variables included in the OS, only prior VTE was significantly associated with the 6-month risk of recurrent VTE (SHR 4.39; 95% CI 1.13–17.04). When pooling data from all studies evaluating this score for predicting VTE recurrence in cancer patients (7 studies, 3413 patients), the OS estimated pooled AUROC was 0.59 (95%CI 0.56–0.62), and its accuracy was 55.7%. The present findings do not support the use of the OS to assess the risk of recurrent VTE in cancer patients. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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13 pages, 569 KiB  
Article
Prognostic Factors for Mortality in Acute Mesenteric Ischemia
by Carlos Constantin Otto, Zoltan Czigany, Daniel Heise, Philipp Bruners, Drosos Kotelis, Sven Arke Lang, Tom Florian Ulmer, Ulf Peter Neumann, Christian Klink and Jan Bednarsch
J. Clin. Med. 2022, 11(13), 3619; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11133619 - 23 Jun 2022
Cited by 9 | Viewed by 2112
Abstract
Postoperative mortality in patients undergoing surgical and/or interventional treatment for acute mesenteric ischemia (AMI) has remained an unsolved problem in recent decades. Here, we investigated clinical predictors of postoperative mortality in a large European cohort of patients undergoing treatment for AMI. In total, [...] Read more.
Postoperative mortality in patients undergoing surgical and/or interventional treatment for acute mesenteric ischemia (AMI) has remained an unsolved problem in recent decades. Here, we investigated clinical predictors of postoperative mortality in a large European cohort of patients undergoing treatment for AMI. In total, 179 patients who underwent surgical and/or interventional treatment for AMI between 2009 and 2021 at our institution were included in this analysis. Associations between postoperative mortality and various clinical variables were assessed using univariate and multivariable binary logistic regression analysis. Most of the patients were diagnosed with arterial ischemia (AI; n = 104), while venous ischemia (VI; n = 21) and non-occlusive mesenteric ischemia (NOMI; n = 54) were present in a subset of patients. Overall inhouse mortality was 55.9% (100/179). Multivariable analyses identified leukocytes (HR = 1.08; p = 0.008), lactate (HR = 1.25; p = 0.01), bilirubin (HR = 2.05; p = 0.045), creatinine (HR = 1.48; p = 0.039), etiology (AI, VI or NOMI; p = 0.038) and portomesenteric vein gas (PMVG; HR = 23.02; p = 0.012) as independent predictors of postoperative mortality. In a subanalysis excluding patients with fatal prognosis at the first surgical exploration (n = 24), leukocytes (HR = 1.09; p = 0.004), lactate (HR = 1.27; p = 0.003), etiology (AI, VI or NOMI; p = 0.006), PMVG (HR = 17.02; p = 0.018) and intraoperative FFP transfusion (HR = 4.4; p = 0.025) were determined as independent predictors of postoperative mortality. Further, the risk of fatal outcome changed disproportionally with increased preoperative lactate values. The clinical outcome of patients with AMI was determined using a combination of pre- and intraoperative clinical and radiological characteristics. Serum lactate appears to be of major clinical importance as the risk of fatal outcome increases significantly with higher lactate values. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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Review

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10 pages, 283 KiB  
Review
COVID-19 and the Response to Antiplatelet Therapy
by Tomáš Bolek, Matej Samoš, Jakub Jurica, Lucia Stančiaková, Martin Jozef Péč, Ingrid Škorňová, Peter Galajda, Ján Staško, Marián Mokáň and Peter Kubisz
J. Clin. Med. 2023, 12(5), 2038; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12052038 - 04 Mar 2023
Cited by 4 | Viewed by 1541
Abstract
The coronavirus SARS-CoV2 disease (COVID-19) is connected with significant morbidity and mortality (3.4%), disorders in hemostasis, including coagulopathy, activation of platelets, vascular injury, and changes in fibrinolysis, which may be responsible for an increased risk of thromboembolism. Many studies demonstrated relatively high rates [...] Read more.
The coronavirus SARS-CoV2 disease (COVID-19) is connected with significant morbidity and mortality (3.4%), disorders in hemostasis, including coagulopathy, activation of platelets, vascular injury, and changes in fibrinolysis, which may be responsible for an increased risk of thromboembolism. Many studies demonstrated relatively high rates of venous and arterial thrombosis related to COVID-19. The incidence of arterial thrombosis in severe/critically ill intensive care unit–admitted COVID-19 patients appears to be around 1%. There are several ways for the activation of platelets and coagulation that may lead to the formation of thrombi, so it is challenging to make a decision about optimal antithrombotic strategy in patients with COVID-19. This article reviews the current knowledge about the role of antiplatelet therapy in patients with COVID-19. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
15 pages, 692 KiB  
Review
Resistance on the Latest Oral and Intravenous P2Y12 ADP Receptor Blockers in Patients with Acute Coronary Syndromes: Fact or Myth?
by Peter Blaško, Matej Samoš, Tomáš Bolek, Lucia Stančiaková, Ingrid Škorňová, Martin Jozef Péč, Jakub Jurica, Ján Staško and Marián Mokáň
J. Clin. Med. 2022, 11(23), 7211; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11237211 - 04 Dec 2022
Cited by 2 | Viewed by 1732
Abstract
Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called “high on-treatment platelet reactivity” [...] Read more.
Novel P2Y12 ADP receptor blockers (ADPRB) should be preferred in dual-antiplatelet therapy in patients with acute coronary syndrome. Nevertheless, there are still patients who do not respond optimally to novel ADP receptor blocker therapy, and this nonoptimal response (so-called “high on-treatment platelet reactivity” or “resistance”) could be connected with increased risk of adverse ischemic events, such as myocardial re-infarction, target lesion failure and stent thrombosis. In addition, several risk factors have been proposed as factors associated with the phenomenon of inadequate response on novel ADPRB. These include obesity, multivessel coronary artery disease, high pre-treatment platelet reactivity and impaired metabolic status for prasugrel, as well as elderly, concomitant therapy with beta-blockers, morphine and platelet count for ticagrelor. There is no literature report describing nonoptimal therapeutic response on cangrelor, and cangrelor therapy seems to be a possible approach for overcoming HTPR on prasugrel and ticagrelor. However, the optimal therapeutic management of “resistance” on novel ADPRB is not clear and this issue requires further research. This narrative review article discusses the phenomenon of high on-treatment platelet reactivity on novel ADPRB, its importance in clinical practice and approaches for its therapeutic overcoming. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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9 pages, 548 KiB  
Review
Tailored Direct Oral Anticoagulation in Patients with Atrial Fibrillation: The Future of Oral Anticoagulation?
by Matej Samoš, Tomáš Bolek, Lucia Stančiaková, Martin Jozef Péč, Kristína Brisudová, Ingrid Škorňová, Ján Staško, Marián Mokáň and Peter Kubisz
J. Clin. Med. 2022, 11(21), 6369; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11216369 - 28 Oct 2022
Cited by 5 | Viewed by 1374
Abstract
Direct oral anticoagulants (DOAC) are currently the drug of choice for drug prevention of stroke or systemic embolism in patients with atrial fibrillation (AF). However, repeated ischemic stroke or systemic embolism and bleeding while on DOAC is still a challenging clinical phenomenon in [...] Read more.
Direct oral anticoagulants (DOAC) are currently the drug of choice for drug prevention of stroke or systemic embolism in patients with atrial fibrillation (AF). However, repeated ischemic stroke or systemic embolism and bleeding while on DOAC is still a challenging clinical phenomenon in the management of future long-term anticoagulation. It is not known whether tailoring the DOAC therapy to achieve optimal therapeutic drug levels could improve the clinical course of DOAC therapy. To be able to tailor the therapy, it is necessary to have a valid laboratory method for DOAC level assessment, to be aware of factors influencing DOAC levels and to have clinical options to tailor the treatment. Furthermore, the data regarding clinical efficacy/safety of tailored DOAC regimes are still lacking. This article reviews the current data on tailored direct oral anticoagulation in patients with AF. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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28 pages, 6211 KiB  
Review
Patients with Bicuspid Aortopathy and Aortic Dilatation
by Francesco Nappi, Omar Giacinto, Mario Lusini, Marialuisa Garo, Claudio Caponio, Antonio Nenna, Pierluigi Nappi, Juliette Rousseau, Cristiano Spadaccio and Massimo Chello
J. Clin. Med. 2022, 11(20), 6002; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11206002 - 11 Oct 2022
Cited by 7 | Viewed by 3193
Abstract
(1) Background: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. Alteration of ascending aorta diameter is a consequence of shear stress alterations due to haemodynamic abnormalities developed from inadequate valve cusp coaptation. (2) Objective: This narrative review aims to discuss [...] Read more.
(1) Background: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. Alteration of ascending aorta diameter is a consequence of shear stress alterations due to haemodynamic abnormalities developed from inadequate valve cusp coaptation. (2) Objective: This narrative review aims to discuss anatomical, pathophysiological, genetical, ultrasound, and radiological aspects of BAV disease, focusing on BAV classification related to imaging patterns and flux models involved in the onset and developing vessel dilatation. (3) Methods: A comprehensive search strategy was implemented in PubMed from January to May 2022. English language articles were selected independently by two authors and screened according to the following criteria. (4) Key Contents and Findings: Ultrasound scan is the primary step in the diagnostic flowchart identifying structural and doppler patterns of the valve. Computed tomography determines aortic vessel dimensions according to the anatomo-pathology of the valve. Magnetic resonance identifies hemodynamic alterations. New classifications and surgical indications derive from these diagnostic features. Currently, indications correlate morphological results, dissection risk factors, and genetic alterations. Surgical options vary from aortic valve and aortic vessel substitution to aortic valve repair according to the morphology of the valve. In selected patients, transcatheter aortic valve replacement has an even more impact on the treatment choice. (5) Conclusions: Different imaging approaches are an essential part of BAV diagnosis. Morphological classifications influence the surgical outcome. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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12 pages, 1336 KiB  
Review
Blood Biomarkers for Triaging Patients for Suspected Stroke: Every Minute Counts
by Radhika Kiritsinh Jadav, Reza Mortazavi and Kwang Choon Yee
J. Clin. Med. 2022, 11(14), 4243; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11144243 - 21 Jul 2022
Cited by 1 | Viewed by 2583
Abstract
Early stroke diagnosis remains a big challenge in healthcare partly due to the lack of reliable diagnostic blood biomarkers, which in turn leads to increased rates of mortality and disability. Current screening methods are optimised to identify patients with a high risk of [...] Read more.
Early stroke diagnosis remains a big challenge in healthcare partly due to the lack of reliable diagnostic blood biomarkers, which in turn leads to increased rates of mortality and disability. Current screening methods are optimised to identify patients with a high risk of cardio-vascular disease, especially among the elderly. However, in young adults and children, these methods suffer low sensitivity and specificity and contribute to further delays in their triage and diagnosis. Accordingly, there is an urgent need to develop reliable blood biomarkers for triaging patients suspected of stroke in all age groups, especially children and young adults. This review explores some of the existing blood biomarkers, as single biomarkers or biomarker panels, and examines their sensitivity and specificity for predicting stroke. A review was performed on PubMed and Web of Science for journal articles published in English during the period 2001 to 2021, which contained information regarding biomarkers of stroke. In this review article, we provide comparative information on the availability, clinical usefulness, and time-window periods of seven single blood biomarkers and five biomarker panels that have been used for predicting stroke in emergency situations. The outcomes of this review can be used in future research for developing more effective stroke biomarkers. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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8 pages, 656 KiB  
Review
Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México
by Claudia Minutti-Zanella, Laura Villarreal-Martínez and Guillermo J. Ruiz-Argüelles
J. Clin. Med. 2022, 11(14), 4100; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11144100 - 15 Jul 2022
Cited by 2 | Viewed by 1638
Abstract
Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined [...] Read more.
Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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16 pages, 1585 KiB  
Review
Non-Lipid Effects of PCSK9 Monoclonal Antibodies on Vessel Wall
by Sabina Ugovšek and Miran Šebeštjen
J. Clin. Med. 2022, 11(13), 3625; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11133625 - 23 Jun 2022
Cited by 7 | Viewed by 2188
Abstract
Elevated low density lipoprotein (LDL) cholesterol and lipoprotein(a) (Lp(a)) levels have an important role in the development and progression of atherosclerosis, followed by cardiovascular events. Besides statins and other lipid-modifying drugs, PCSK9 monoclonal antibodies are known to reduce hyperlipidemia. PCSK9 monoclonal antibodies decrease [...] Read more.
Elevated low density lipoprotein (LDL) cholesterol and lipoprotein(a) (Lp(a)) levels have an important role in the development and progression of atherosclerosis, followed by cardiovascular events. Besides statins and other lipid-modifying drugs, PCSK9 monoclonal antibodies are known to reduce hyperlipidemia. PCSK9 monoclonal antibodies decrease LDL cholesterol levels through inducing the upregulation of the LDL receptors and moderately decrease Lp(a) levels. In addition, PCSK9 monoclonal antibodies have shown non-lipid effects. PCSK9 monoclonal antibodies reduce platelet aggregation and activation, and increase platelet responsiveness to acetylsalicylic acid. Evolocumab as well as alirocumab decrease an incidence of venous thromboembolism, which is associated with the decrease of Lp(a) values. Besides interweaving in haemostasis, PCSK9 monoclonal antibodies play an important role in reducing the inflammation and improving the endothelial function. The aim of this review is to present the mechanisms of PCSK9 monoclonal antibodies on the aforementioned risk factors. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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15 pages, 1050 KiB  
Review
Risk Stratification in Patients with Acute Pulmonary Embolism: Current Evidence and Perspectives
by Antonio Leidi, Stijn Bex, Marc Righini, Amandine Berner, Olivier Grosgurin and Christophe Marti
J. Clin. Med. 2022, 11(9), 2533; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11092533 - 30 Apr 2022
Cited by 16 | Viewed by 7534
Abstract
Risk stratification is one of the cornerstones of the management of acute pulmonary embolism (PE) and determines the choice of both diagnostic and therapeutic strategies. The first step is the identification of patent circulatory failure, as it is associated with a high risk [...] Read more.
Risk stratification is one of the cornerstones of the management of acute pulmonary embolism (PE) and determines the choice of both diagnostic and therapeutic strategies. The first step is the identification of patent circulatory failure, as it is associated with a high risk of immediate mortality and requires a rapid diagnosis and prompt reperfusion. The second step is the estimation of 30-day mortality based on clinical parameters (e.g., original and simplified version of the pulmonary embolism severity index): low-risk patients without right ventricular dysfunction are safely managed with ambulatory anticoagulation. The remaining group of hemodynamically stable patients, labeled intermediate-risk PE, requires hospital admission, even if most of them will heal without complications. In recent decades, efforts have been made to identify a subgroup of patients at an increased risk of adverse outcomes (intermediate-high-risk PE), who might benefit from a more aggressive approach, including reperfusion therapies and admission to a monitored unit. The cur-rent approach, combining markers of right ventricular dysfunction and myocardial injury, has an insufficient positive predictive value to guide primary thrombolysis. Sensitive markers of circulatory failure, such as plasma lactate, have shown interesting prognostic accuracy and may play a central role in the future. Furthermore, the improved security of reduced-dose thrombolysis may enlarge the indication of this treatment to selected intermediate–high-risk PE. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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Jump to: Research, Review

14 pages, 957 KiB  
Systematic Review
Endovascular Treatment of Intracranial Vein and Venous Sinus Thrombosis—A Systematic Review
by Philipp Bücke, Victoria Hellstern, Alexandru Cimpoca, José E. Cohen, Thomas Horvath, Oliver Ganslandt, Hansjörg Bäzner and Hans Henkes
J. Clin. Med. 2022, 11(14), 4215; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11144215 - 20 Jul 2022
Cited by 9 | Viewed by 6621
Abstract
Background: Cerebral venous sinus or vein thromboses (SVT) are treated with heparin followed by oral anticoagulation. Even after receiving the best medical treatment, numerous patients experience neurological deterioration, intracerebral hemorrhage or brain edema. Debate regarding whether endovascular treatment (EVT) is beneficial in such [...] Read more.
Background: Cerebral venous sinus or vein thromboses (SVT) are treated with heparin followed by oral anticoagulation. Even after receiving the best medical treatment, numerous patients experience neurological deterioration, intracerebral hemorrhage or brain edema. Debate regarding whether endovascular treatment (EVT) is beneficial in such severe cases remains ongoing. This systematic review summarizes the current evidence supporting the use of EVT for SVT on the basis of case presentations, with a focus on patient selection, treatment strategies and the effects of the COVID-19 pandemic. Methods: This systemic literature review included randomized controlled trials (RCTs) and retrospective observational data analyzing five or more patients. Follow-up information (modified Rankin scale (mRS)) was required to be provided (individual patient data). Results: 21 records (n = 405 patients; 1 RCT, 20 observational studies) were identified. EVT was found to be feasible and safe in a highly selected patient cohort but was not associated with an increase in good functional outcomes (mRS 0–2) in RCT data. In observational data, good functional outcomes were frequently observed despite an anticipated poor prognosis. Conclusion: The current evidence does not support the routine incorporation of EVT in SVT treatment. However, in a patient cohort prone to poor prognosis, EVT might be a reasonable therapeutic option. Further studies determining the patients at risk, choice of methods and devices, and timing of treatment initiation are warranted. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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30 pages, 40747 KiB  
Systematic Review
Insights into the Role of Neutrophils and Neutrophil Extracellular Traps in Causing Cardiovascular Complications in Patients with COVID-19: A Systematic Review
by Francesco Nappi, Francesca Bellomo and Sanjeet Singh Avtaar Singh
J. Clin. Med. 2022, 11(9), 2460; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11092460 - 27 Apr 2022
Cited by 7 | Viewed by 2737
Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has resulted in significant mortality and burdening of healthcare resources. While initially noted as a pulmonary pathology, subsequent studies later identified cardiovascular involvement with high mortalities reported in specific cohorts of [...] Read more.
Background: The coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has resulted in significant mortality and burdening of healthcare resources. While initially noted as a pulmonary pathology, subsequent studies later identified cardiovascular involvement with high mortalities reported in specific cohorts of patients. While cardiovascular comorbidities were identified early on, the exact manifestation and etiopathology of the infection remained elusive. This systematic review aims to investigate the role of inflammatory pathways, highlighting several culprits including neutrophil extracellular traps (NETs) which have since been extensively investigated. Method: A search was conducted using three databases (MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations and EMBASE). Data from randomized controlled trials (RCT), prospective series, meta-analyses, and unmatched observational studies were considered for the processing of the algorithm and treatment of inflammatory response during SARS-CoV-2 infection. Studies without the SARS-CoV-2 Infection period and case reports were excluded. Results: A total of 47 studies were included in this study. The role of the acute inflammatory response in the propagation of the systemic inflammatory sequelae of the disease plays a major part in determining outcomes. Some of the mechanisms of activation of these pathways have been highlighted in previous studies and are highlighted. Conclusion: NETs play a pivotal role in the pathogenesis of the inflammatory response. Despite moving into the endemic phase of the disease in most countries, COVID-19 remains an entity that has not been fully understood with long-term effects remaining uncertain and requiring ongoing monitoring and research. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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6 pages, 1530 KiB  
Case Report
Rare Source of Embolism in a Young Patient: Case Report and Literature Review
by Marianna Vachalcová, Monika Jankajová, Marta Jakubová, Karolina Angela Sieradzka, Tibor Porubän, Gabriel Valočik, Peter Šafár, Daniela Ondušová, Ján Petruš and Ingrid Schusterová
J. Clin. Med. 2022, 11(7), 2038; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11072038 - 05 Apr 2022
Viewed by 1718
Abstract
We present a case of a 31-year-old patient, smoker, with no previous medical history, presenting with acute limb ischemia and infarction of the spleen due to peripheral embolism. The source of embolism was thrombi formations in the left ventricular cavity, located in the [...] Read more.
We present a case of a 31-year-old patient, smoker, with no previous medical history, presenting with acute limb ischemia and infarction of the spleen due to peripheral embolism. The source of embolism was thrombi formations in the left ventricular cavity, located in the area of the regional wall motions abnormalities. CT and coronary angiography confirmed the total occlusion of the left anterior descending artery with collateralization. The patient underwent acute bilateral embolectomy of the iliac, femoral, and popliteal arteries. Subsequently, cardiothoracic surgery was indicated with coronary bypass surgery and extirpation of left ventricular masses, later confirmed as thrombus by pathology characteristics. Hematological examinations proved homozygous thrombophilia, and the patient was indicated for lifelong anticoagulation therapy. Full article
(This article belongs to the Special Issue Management of Venous and Arterial Thrombosis)
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