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Medicina
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Thrombotic Disorders and Antithrombotic Treatments
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Thrombotic Disorders and Antithrombotic Treatments

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 28981

Special Issue Editor

Dr. Pierpaolo Di Micco

E-Mail Website
Guest Editor
UOC Medicina, Fatebenefratelli Hospital of Naples, 80131 Naples, 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,

In daily clinical practice, thrombotic disorders may appear as transversal events that may occur in provoked and unprovoked clinical forms or during\after other underlying clinical conditions.

For this reason, venous thromboembolism (VTE) may be divided into provoked VTE or unprovoked VTE (a VTE event that appears without recent contact with common thrombotic risk factors). This classification is relevant, because the duration of anticoagulant treatment differs in cases of provoked or unprovoked VTE. In this way, provoked VTE is a VTE event that appears in the presence of thrombotic risk factors. Common thrombotic risk factors have been identified by international guidelines as clinical conditions that need pharmacological prophylaxis to prevent VTE (e.g., recent surgery, recent hypomobilization, pregnancy, hormonal treatment, molecular inherited/acquired thrombophilia, and cancer and its therapy). Yet, according to the above reported guidelines and clinical scores, nearly 40% of VTE events may be considered unprovoked or idiopathic, and this may create too many difficulties in the management of prolonged antithrombotic treatments because of their relevant risk of bleeding. On the other hand, other clinical conditions, such as inflammatory bowel diseases, immunopathological diseases, and other molecular defects (e.g., hypofibrinolysis), may be associated with VTE, creating further confusion on the duration of antithrombotic treatments after a VTE in the presence of these predisposing conditions.

Furthermore, other coagulopathies with elevated incidences of morbidity and mortality for inpatients, such as disseminated intravascular coagulation, are frequently associated with underlying clinical conditions; however, primary and secondary preventions are less studied.

In order to increase knowledge in this field, this Special Issue of Medicina on “Thrombotic Disorders and Antithrombotic Treatments” is dedicated to all authors that are interested in the effective daily clinical practices and treatments of thrombotic diseases.

Dr. Pierpaolo Di Micco
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. Medicina 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 1800 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
  • pulmonary embolism
  • disseminated intravascular coagulation
  • hypercoagulable state
  • antithrombotics
  • anticoagulants
  • thrombophilia

Published Papers (11 papers)

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Editorial

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2 pages, 207 KiB  
Editorial
Thrombotic Disorders and Antithrombotic Treatments Special Issue
by Pierpaolo Di Micco
Medicina 2022, 58(2), 229; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina58020229 - 02 Feb 2022
Cited by 1 | Viewed by 1115
Abstract
Thrombotic disorders include a variety of clinical diseases that are common causes of mortality and morbidity in western countries [...] Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)

Research

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9 pages, 294 KiB  
Article
Molecular Analysis of Prothrombotic Gene Variants in Patients with Acute Ischemic Stroke and with Transient Ischemic Attack
by Gustavo Cernera, Marika Comegna, Monica Gelzo, Marcella Savoia, Dario Bruzzese, Mauro Mormile, Federica Zarrilli, Felice Amato, Pierpaolo Di Micco and Giuseppe Castaldo
Medicina 2021, 57(7), 723; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57070723 - 17 Jul 2021
Cited by 8 | Viewed by 1832
Abstract
Background and objectives: ischemic stroke (IS) is among the most frequent causes of death worldwide; thus, it is of paramount relevance to know predisposing factors that may help to identify and treat the high-risk subjects. Materials and Methods:we tested nine variants [...] Read more.
Background and objectives: ischemic stroke (IS) is among the most frequent causes of death worldwide; thus, it is of paramount relevance to know predisposing factors that may help to identify and treat the high-risk subjects. Materials and Methods:we tested nine variants in genes involved in thrombotic pathway in 282 patients that experienced IS and 87 that had transient ischemic attacks (TIA) in comparison to 430 subjects from the general population (GP) of the same geographic area (southern Italy). We included cases of young and child IS to evaluate the eventual differences in the role of the analyzed variants. Results: we did not observe significant differences between TIA and the GP for any of the variants, while the allele frequencies of methylene-tetrahydrofolate reductase (MTHFR) C677T, beta-fibrinogen -455G>A and factor (FXIII) V34L were significantly higher in patients with IS than in the subjects from the GP. No significant interaction was observed with sex. Conclusions: the present data argue that some gene variants have a role in IS and this appears to be an interesting possibility to be pursued in large population studies to help design specific strategies for IS prevention. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
11 pages, 1535 KiB  
Article
The Impact of Novel Anticoagulants on the Upper Gastrointestinal Tract Mucosa
by Lubomir Mihalkanin and Branislav Stancak
Medicina 2020, 56(7), 363; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56070363 - 21 Jul 2020
Cited by 13 | Viewed by 2717
Abstract
Background and objectives: Although treatment with novel oral non-vitamin K antagonist 3anticoagulants (NOACs) is associated with an overall decrease in hemorrhagic complications compared to warfarin, the incidence of gastrointestinal bleeding remains contradictory. Materials and Methods: After the exclusion of patients with pre-existing pathological [...] Read more.
Background and objectives: Although treatment with novel oral non-vitamin K antagonist 3anticoagulants (NOACs) is associated with an overall decrease in hemorrhagic complications compared to warfarin, the incidence of gastrointestinal bleeding remains contradictory. Materials and Methods: After the exclusion of patients with pre-existing pathological lesions in the upper gastrointestinal tract (GIT) on esophageal-gastroduodenoscopy (EGD) at entry, a cohort of 80 patients (mean age of 74.8 ± 2.0 years) was randomly divided into four equivalent groups, treated with dabigatran, rivaroxaban, apixaban, or warfarin. Patients were prospectively followed up for three months of treatment, with a focus on anamnestic and endoscopic signs of bleeding. In addition, bleeding risk factors were evaluated. Results: In none of the patients treated with warfarin or NOACs was any serious or clinically significant bleeding recorded within the follow-up period. The incidence of clinical bleeding and endoscopically detected bleeding in the upper GT after three months of treatment was not statistically different among groups (χ2 = 2.8458; p = 0.41608). The presence of Helicobacter pylori (HP) was a risk factor for upper GIT bleeding (p < 0.05), while the use of proton pump inhibitors (PPIs) was a protective factor (p = 0.206; Spearman’s correlation coefficient = 0.205). We did not record any post-biopsy continued bleeding. Conclusions: No significant GIT bleeding was found in any of the treatment groups, so we consider it beneficial to perform routine EGD before the initiation of any anticoagulant therapy in patients with an increased risk of upper GIT bleeding. Detection and eradication of HP as well as preventive PPI treatment may mitigate the occurrence of endoscopic bleeding. Endoscopic biopsy during the NOAC treatment is safe. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
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10 pages, 1014 KiB  
Article
Factors Associated with Procedural Thromboembolisms after Mechanical Thrombectomy for Acute Ischemic Stroke
by Taek Min Nam, Ji Hwan Jang, Young Zoon Kim, Kyu Hong Kim and Seung Hwan Kim
Medicina 2020, 56(7), 353; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56070353 - 16 Jul 2020
Cited by 5 | Viewed by 1840
Abstract
Background and objective: Procedural thromboembolisms after mechanical thrombectomy (MT) for acute ischemic stroke has rarely been studied. We retrospectively evaluated factors associated with procedural thromboembolisms after MT using diffusion-weight imaging (DWI) within 2 days of MT. Materials and Methods: From January 2018 to [...] Read more.
Background and objective: Procedural thromboembolisms after mechanical thrombectomy (MT) for acute ischemic stroke has rarely been studied. We retrospectively evaluated factors associated with procedural thromboembolisms after MT using diffusion-weight imaging (DWI) within 2 days of MT. Materials and Methods: From January 2018 to March 2020, 78 patients with acute ischemic stroke who underwent MT were evaluated using DWI. Procedural thromboembolisms were defined as new cerebral infarctions in other territories from the occluded artery on DWI after MT. Results: Procedural thromboembolisms were observed on DWI in 16 patients (20.5%). Procedural thromboembolisms were associated with old age (73.8 ± 8.18 vs. 66.8 ± 11.2 years, p = 0.021), intravenous (IV) thrombolysis (12 out of 16 (75.0%) vs. 25 out of 62 (40.3%), p = 0.023), heparinization (4 out of 16 (25.0%) vs. 37 out of 62 (59.7%), p = 0.023), and longer procedural time (90.9 ± 35.6 vs. 64.4 ± 33.0 min, p = 0.006). Multivariable logistic regression analysis revealed that procedural thromboembolisms were independently associated with procedural time (adjusted odds ratio (OR); 1.020, 95% confidence interval (CI); 1.002–1.039, p = 0.030) and IV thrombolysis (adjusted OR; 4.697, 95% CI; 1.223–18.042, p = 0.024). The cutoff value of procedural time for predicting procedural thromboembolisms was ≥71 min (area under the curve; 0.711, 95% CI; 0.570–0.851, p = 0.010). Conclusions: Procedural thromboembolisms after MT for acute ischemic stroke are significantly associated with longer procedural time and IV thrombolysis. This study suggests that patients with IV thrombolysis and longer procedural time (≥71 min) are at a higher risk of procedural thromboembolisms after MT for acute ischemic stroke. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
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Review

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12 pages, 526 KiB  
Review
Perioperative Management of Chronic Antithrombotic Agents in Elective Hip and Knee Arthroplasty
by Daniel C. Santana, Matthew J. Hadad, Ahmed Emara, Alison K. Klika, Wael Barsoum, Robert M. Molloy, Viktor E. Krebs, Michael R. Bloomfield and Nicolas S. Piuzzi
Medicina 2021, 57(2), 188; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57020188 - 23 Feb 2021
Cited by 7 | Viewed by 2865
Abstract
Total hip and knee arthroplasty are common major orthopedic operations being performed on an increasing number of patients. Many patients undergoing total joint arthroplasty (TJA) are on chronic antithrombotic agents due to other medical conditions, such as atrial fibrillation or acute coronary syndrome. [...] Read more.
Total hip and knee arthroplasty are common major orthopedic operations being performed on an increasing number of patients. Many patients undergoing total joint arthroplasty (TJA) are on chronic antithrombotic agents due to other medical conditions, such as atrial fibrillation or acute coronary syndrome. Given the risk of bleeding associated with TJAs, as well as the risk of thromboembolic events in the post-operative period, the management of chronic antithrombotic agents perioperatively is critical to achieving successful outcomes in arthroplasty. In this review, we provide a concise overview of society guidelines regarding the perioperative management of chronic antithrombotic agents in the setting of elective TJAs and summarize the recent literature that may inform future guidelines. Ultimately, antithrombotic regimen management should be patient-specific, in consultation with cardiology, internal medicine, hematology, and other physicians who play an essential role in perioperative care. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
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11 pages, 1391 KiB  
Review
Serological Parameters and Vascular Investigation for a Better Assessment in DVT during Pregnancy—A Systematic Review
by Catalina Filip, Demetra Gabriela Socolov, Elena Albu, Cristiana Filip, Roxana Serban and Radu Florin Popa
Medicina 2021, 57(2), 160; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57020160 - 10 Feb 2021
Cited by 11 | Viewed by 2633
Abstract
Pregnancy and the postpartum period represent a condition characterized by a thrombotic predisposition. The majority of pregnant women do not face acute or severe thrombotic events. In general, mild inconveniences such as leg swelling or moderately painful thrombotic events (phlebitis) are encountered. However, [...] Read more.
Pregnancy and the postpartum period represent a condition characterized by a thrombotic predisposition. The majority of pregnant women do not face acute or severe thrombotic events. In general, mild inconveniences such as leg swelling or moderately painful thrombotic events (phlebitis) are encountered. However, when pregnancy is associated with inherited or acquired deficits that affect homeostasis, the risk of acute or even life-threatening events can increase significantly. The major consequence is the loss of the fetus or the venous thromboembolism that endangers the mother’s life. Venous thromboembolism is caused by deep vein thrombosis, therefore timely detection and especially the assessment of the extent of the thrombotic event are crucial. In this paper we have summarized the most important paraclinical investigations. The study emphasizes the importance of selecting the methods of investigation. The right choice allows establishing a correct diagnosis and individualizing the treatment. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
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14 pages, 799 KiB  
Review
An Update on Venous Thromboembolism Rates and Prophylaxis in Hip and Knee Arthroplasty in 2020
by Daniel C. Santana, Ahmed K. Emara, Melissa N. Orr, Alison K. Klika, Carlos A. Higuera, Viktor E. Krebs, Robert M. Molloy and Nicolas S. Piuzzi
Medicina 2020, 56(9), 416; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56090416 - 19 Aug 2020
Cited by 40 | Viewed by 5918
Abstract
Patients undergoing total hip and knee arthroplasty are at high risk for venous thromboembolism (VTE) with an incidence of approximately 0.6–1.5%. Given the high volume of these operations, with approximately one million performed annually in the U.S., the rate of VTE represents a [...] Read more.
Patients undergoing total hip and knee arthroplasty are at high risk for venous thromboembolism (VTE) with an incidence of approximately 0.6–1.5%. Given the high volume of these operations, with approximately one million performed annually in the U.S., the rate of VTE represents a large absolute number of patients. The rate of VTE after total hip arthroplasty has been stable over the past decade, although there has been a slight reduction in the rate of deep venous thrombosis (DVT), but not pulmonary embolism (PE), after total knee arthroplasty. Over this time, there has been significant research into the optimal choice of pharmacologic VTE prophylaxis for individual patients, with the objective to reduce the rate of VTE while minimizing adverse side effects such as bleeding. Recently, aspirin has emerged as a promising prophylactic agent for patients undergoing arthroplasty due to its similar efficacy and good safety profile compared to other pharmacologic agents. However, there is no evidence to date that clearly demonstrates the superiority of any given prophylactic agent. Therefore, this review discusses (1) the current prevalence and trends in VTE after total hip and knee arthroplasty and (2) provides an update on pharmacologic VTE prophylaxis in regard to aspirin usage. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
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Other

6 pages, 845 KiB  
Case Report
May-Thurner Syndrome Is Aggravated by Pregnancy
by Kuntharee Traisrisilp, Manatsawee Manopunya, Tanop Srisuwan, Wisit Chankhunaphas and Theera Tongsong
Medicina 2021, 57(3), 222; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57030222 - 01 Mar 2021
Cited by 3 | Viewed by 2736
Abstract
This study aims to emphasize that asymptomatic patients with undiagnosed and asymptomatic May-Thurner syndrome (MTS) may firstly develop severe compression during pregnancy. A 40-year-old woman, G1P0, at 22 weeks of twin gestation presented with left lower extremity edema and pain. One twin was [...] Read more.
This study aims to emphasize that asymptomatic patients with undiagnosed and asymptomatic May-Thurner syndrome (MTS) may firstly develop severe compression during pregnancy. A 40-year-old woman, G1P0, at 22 weeks of twin gestation presented with left lower extremity edema and pain. One twin was structurally normal while the other had bilateral renal agenesis with oligohydramnios. Magnetic resonance venography (MRV) revealed severe compression of the left iliac vein by the right iliac artery without evidence of deep vein thrombosis (DVT). Conservative treatment with anticoagulant prophylaxis was instituted throughout the rest of pregnancy and postpartum period. She was also complicated with severe pre-eclampsia, a cesarean section was performed due to a prolapsed cord at 27 weeks of gestation, and she gave birth to a surviving baby weighing 1100 g. In conclusion, this case report provides evidence that pregnancy can disclose a subtle May-Thurner anatomy to be symptomatic without DVT. Successful pregnancy outcomes could be achieved with conservative treatment and anticoagulant prophylaxis. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
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4 pages, 538 KiB  
Case Report
Resolution of Disseminated Intravascular Coagulation in a Patient with COVID-19 and Associated Sepsis—Induced Neutropenia
by Pierpaolo Di Micco, Michele Imparato, Giuseppe Lubrano, Donatella Iannuzzo, Luca Fontanella, Lucio Improta, Maria Rita Poggiano, Ciro Salzano, Alessio Rodolico and Andrea Fontanella
Medicina 2021, 57(2), 106; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57020106 - 24 Jan 2021
Cited by 4 | Viewed by 1784
Abstract
COVID-19 has been associated with a hypercoagulable state and thrombotic events. Venous thromboembolism has been the most commonly reported type of thrombosis but also arterial thrombosis and disseminated intravascular coagulation in inpatients have been described frequently in several clinical experiences. Patients with COVID-19, [...] Read more.
COVID-19 has been associated with a hypercoagulable state and thrombotic events. Venous thromboembolism has been the most commonly reported type of thrombosis but also arterial thrombosis and disseminated intravascular coagulation in inpatients have been described frequently in several clinical experiences. Patients with COVID-19, because of its tendency to induce leucopenia and overlapping of bacterial infection, may experience sudden disseminated intravascular coagulation (DIC), as in the case that we report here. However, early diagnosis and treatment may be associated with positive resolution of these severe complications. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
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3 pages, 231 KiB  
Letter
Venous Thromboembolism and Its Association with COVID-19: Still an Open Debate
by Pierpaolo Di Micco, Vincenzo Russo and Corrado Lodigiani
Medicina 2020, 56(10), 506; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56100506 - 27 Sep 2020
Cited by 12 | Viewed by 1920
Abstract
Asreported by the World Health Organization, a novel coronavirus (COVID-19) was identified as the causative virus of new viral pneumonia of unknown etiology by Chinese authorities on 7 January 2020. The virus was named COVID-19 and because of its ability to cause severe [...] Read more.
Asreported by the World Health Organization, a novel coronavirus (COVID-19) was identified as the causative virus of new viral pneumonia of unknown etiology by Chinese authorities on 7 January 2020. The virus was named COVID-19 and because of its ability to cause severe acute respiratory syndrome (i.e., SARS) this infection has also been defined as SARS-CoV2.Furthermore, an association between COVID-19 infection and venous thromboembolism has been reported in several series around the world.For this reason, methods used to improve diagnostic tools, pharmacological thromboprophylaxis and type of anticoagulants are discussed in this expert opinion. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
6 pages, 291 KiB  
Case Report
Novel Splice Site Mutation in the PROS1 Gene in a Polish Patient with Venous Thromboembolism: c.602-2delA, Splice Acceptor Site of Exon 7
by Magdalena Mrożek, Ewa Wypasek, Martine Alhenc-Gelas, Daniel P. Potaczek and Anetta Undas
Medicina 2020, 56(9), 485; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56090485 - 22 Sep 2020
Cited by 4 | Viewed by 2529
Abstract
We identified a novel splice site mutation of the PROS1 gene in a Polish family with protein S (PS) deficiency and explored the molecular pathogenesis of this previously undescribed variant. A novel mutation was detected in a 26-year-old woman with a history of [...] Read more.
We identified a novel splice site mutation of the PROS1 gene in a Polish family with protein S (PS) deficiency and explored the molecular pathogenesis of this previously undescribed variant. A novel mutation was detected in a 26-year-old woman with a history of venous thromboembolism (VTE) provoked by oral contraceptives. Her family history of VTE was positive. The sequence analysis of the PROS1 gene was performed in the proband and the proband’s family. The proband and their asymptomatic father had lower free PS levels (45% and 50%, respectively) and PS activity (48% and 44%, respectively). Total PS levels were normal (65.6% and 62.4%, respectively). The sequence analysis of the PROS1 gene revealed the presence of heterozygous deletion at the nucleotide position c.602-2 in intron 6, just upstream of exon 7, detected in the proband and her father. This variant alters the splice acceptor site of exon 7, and, according to the in silico prediction, it is highly likely to cause in-frame exon 7 skipping. We also presented follow-up data of two other Polish patients with PS deficiency associated with splice site mutations in PROS1 gene. Full article
(This article belongs to the Special Issue Thrombotic Disorders and Antithrombotic Treatments)
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