Thrombosis UpdatePub Date : 2024-04-17DOI: 10.1016/j.tru.2024.100174
Neha Gupta , Mohd Faiz Saifi , Kiesha Wilson , Yohei Hisada , Colin E. Evans
{"title":"The regulation of cancer-associated thrombosis by podoplanin","authors":"Neha Gupta , Mohd Faiz Saifi , Kiesha Wilson , Yohei Hisada , Colin E. Evans","doi":"10.1016/j.tru.2024.100174","DOIUrl":"10.1016/j.tru.2024.100174","url":null,"abstract":"<div><p>The incidence of venous thromboembolism (VTE) in cancer patients is 4–9 fold higher compared with the general population. The mortality rate of patients with cancer and VTE is more than 2-fold greater versus cancer patients without VTE. Given that the pathophysiology of thrombosis in cancer is multi-faceted, investigations of the mechanisms that regulate cancer-associated thrombosis (CAT) could improve the understanding and treatment of CAT. These mechanisms include activation of the coagulation and fibrinolytic systems. Tumor cells activate coagulation by expressing procoagulant molecules, releasing pro-inflammatory and pro-angiogenic cytokines, and adhering to vascular and blood cells. Tumor-secreted and tissue factor-positive extracellular vesicles are another major driver of CAT, while emerging studies have discovered a role for podoplanin (PDPN) in intratumoral thrombosis, hyper-coagulation, and enhanced VTE risk. In this article, we will review studies of PDPN in CAT, which together suggest that PDPN contributes not only to cancer progression and metastasis, but also to CAT. PDPN may therefore represent an attractive putative target for therapies that aim to simultaneously reduce cancer progression and associated VTE.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"15 ","pages":"Article 100174"},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572724000166/pdfft?md5=ea2623379077880bb828768f47664234&pid=1-s2.0-S2666572724000166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140774861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2024-04-16DOI: 10.1016/j.tru.2024.100171
Matthias M. Engelen , Charlotte Van Edom , Andreas Verstraete , Peter Verhamme , Thomas Vanassche
{"title":"The current landscape of factor XI inhibitors","authors":"Matthias M. Engelen , Charlotte Van Edom , Andreas Verstraete , Peter Verhamme , Thomas Vanassche","doi":"10.1016/j.tru.2024.100171","DOIUrl":"10.1016/j.tru.2024.100171","url":null,"abstract":"<div><p>Anticoagulant therapy has always been tightly connected with bleeding risk, as two sides of the same coin. New insights in thrombosis and hemostasis prompted the development of intrinsic pathway inhibitors that promise to uncouple thrombosis and hemostasis. Treating and preventing thrombotic complications without the associated bleeding risk opens up many new possibilities for patients with an unmet need with the current anticoagulant drugs. Many candidate drugs are being investigated in phase I, II, and III clinical trials. In this review, we will introduce the new insights driving this evolution in drug development, whereafter the drugs under development and their clinical trials will be discussed.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"15 ","pages":"Article 100171"},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572724000130/pdfft?md5=1ffcdc411cc22c1641e9c2bdd718dec6&pid=1-s2.0-S2666572724000130-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140769014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2024-04-09DOI: 10.1016/j.tru.2024.100170
Firafan Shuma Teka , Ayana Tadesse Korsa , Habte Gebeyehu Bayisa , Hamba Yigezu Fida , Birbirsa Sefera Senbeta
{"title":"Adverse clinical outcomes of warfarin therapy and predictors among adult outpatients at public hospitals in Nekemte town, western Ethiopia: A retrospective cross-sectional study","authors":"Firafan Shuma Teka , Ayana Tadesse Korsa , Habte Gebeyehu Bayisa , Hamba Yigezu Fida , Birbirsa Sefera Senbeta","doi":"10.1016/j.tru.2024.100170","DOIUrl":"https://doi.org/10.1016/j.tru.2024.100170","url":null,"abstract":"<div><h3>Background</h3><p>Management with warfarin therapy becomes challenging globally due to the increased risk of adverse clinical outcomes from its use. In Africa, warfarin-related bleeding events and thromboembolic complications range from 0.006 % to 59 % and 1.6 %–7.5 %, respectively.</p></div><div><h3>Objectives</h3><p>This study aimed to determine adverse clinical outcomes of warfarin therapy and predictors among adult outpatients at Wallaga University Referral and Nekemte Comprehensive Specialized Hospitals from April 1, 2021 to March 31, 2023.</p></div><div><h3>Methods</h3><p>An institutional-based retrospective cross-sectional study was conducted from June 1 to July 31, 2023, by reviewing the patient's medical charts with warfarin indications. Descriptive statistics such as frequencies, percentages, means, and standard deviations were computed. Bivariable and multivariable logistic regression analyses were performed to check the association between dependent and independent variables. In multivariable logistic regression analysis, an adjusted odds ratio (AOR) with 95 % CI was determined and statistical significance was declared at a p-value <0.05.</p></div><div><h3>Results</h3><p>A total of 402 patients' medical charts with warfarin indications were reviewed. The mean age of the study participants was 38.9 ± 17.9 years and 271(67.4 %) were female patients. Bleeding events 19(4.7 %) and thromboembolic complications 32(8 %) were adverse clinical outcomes of warfarin therapy observed in this study. Warfarin therapy used for 4–6 months (AOR = 3.270; [CI: 1.043–10.252]; p-value = 0.042), hypertension comorbidity (AOR = 3.582; [CI: 1.015–12.642]; p-value = 0.047) and aspirin use (AOR = 5.043; [CI: 1.964–12.948]; p-value = 0.001) were the independent predictors of warfarin related bleeding events. Patients aged 41–64 years were 67.4 % less likely to develop warfarin-related thromboembolic complications than those patients aged 18–40 years (AOR = 0.326; [CI: 0.108–0.983]; p-value = 0.046).</p></div><div><h3>Conclusions</h3><p>Adverse clinical outcomes were found to be observed in less than one-fourth of the study participants in our study. Warfarin use for 4–6 months, hypertension comorbidity, and concomitant use of aspirin were identified as the independent predictors of warfarin-related bleeding events. The age range of 41–64 years was less likely predictive of warfarin-related thromboembolic complications. Institutional-based guidelines and clinical pharmacist involvement in anticoagulation management play a vital role in preventing adverse clinical outcomes.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"15 ","pages":"Article 100170"},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572724000129/pdfft?md5=c82f4634dfec1ac8b6466df11359caf0&pid=1-s2.0-S2666572724000129-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2024-03-27DOI: 10.1016/j.tru.2024.100168
Karlyn A. Martin , Kenzie A. Cameron , Jeffrey A. Linder , Lisa R. Hirschhorn
{"title":"Preventing venous thromboembolism for ambulatory patients with cancer: Developing the form and content of implementation strategies","authors":"Karlyn A. Martin , Kenzie A. Cameron , Jeffrey A. Linder , Lisa R. Hirschhorn","doi":"10.1016/j.tru.2024.100168","DOIUrl":"https://doi.org/10.1016/j.tru.2024.100168","url":null,"abstract":"<div><h3>Background</h3><p>For ambulatory cancer patients receiving systemic chemotherapy, adherence is low to recommended venous thromboembolism (VTE) prevention interventions. Previously, we identified implementation strategies to address barriers to adherence, including (1) conducting clinician education and training; (2) developing and distributing educational materials for clinicians; (3) adapting electronic health records to provide interactive assistance; and (4) developing and distributing educational materials for patients. The objective of this study was to develop these implementation strategies’ form (i.e., how and when) and content (i.e., information conveyed) as a critical step for implementation and dissemination.</p></div><div><h3>Methods</h3><p>To design and develop the form and content of the implementation strategies, we conducted multidisciplinary stakeholder panels with oncology clinicians, pharmacists, and hematologists. Over several panel discussions, we developed a low fidelity prototype. Participants performed preliminary usability testing, simulating patient care encounters. We also conducted interviews with three patients who provided additional feedback.</p></div><div><h3>Results</h3><p>The form and content for each strategy, respectively, included (1) concise training with a slide deck; (2) succinct summary of evidence for the interventions and support for anticoagulation management; (3) automated VTE risk-assessment and clinical decision support, including bleeding risk assessment and anticoagulation options; and (4) patient education resources. During development, audit and feedback was identified as an additional strategy, for which we created report cards to implement.</p></div><div><h3>Conclusion</h3><p>With stakeholder input, we successfully developed the form and content needed to put the implementation strategies into practice. The next step is to study the effect on the uptake of ambulatory VTE prevention recommendations in oncology clinics.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"15 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572724000105/pdfft?md5=1742699345e90e6dcb804b123f54ec8d&pid=1-s2.0-S2666572724000105-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140350779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2024-03-26DOI: 10.1016/j.tru.2024.100169
Antonella Tufano , Antonio Coppola
{"title":"How to manage anticoagulation for cancer-associated thrombosis and atrial fibrillation in cancer","authors":"Antonella Tufano , Antonio Coppola","doi":"10.1016/j.tru.2024.100169","DOIUrl":"10.1016/j.tru.2024.100169","url":null,"abstract":"<div><p>Cancer associated thrombosis (CAT) is the second leading cause of death in oncologic patients and includes both venous thromboembolism (VTE) and arterial thrombotic events (ATE). In addition, cancer patients have an increased risk of developing atrial fibrillation (AF), which represents an additional risk factor for systemic thromboembolism in these patients. Both CAT and AF may be the first presentation of the oncologic disease or develop because of chemotherapy or radiotherapy. The management of the anticoagulation in cancer patients with CAT or AF is challenging, and data on these patients are lacking in specific settings/situations. Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) represent the preferred treatment strategies in CAT, and DOACs in cancer patients with AF. However, the possible drug-drug interactions of DOACs and the bleeding risks in thrombocytopenic patients should be considered. The use of vitamin K antagonists (VKAs) in cancer patients with CAT or AF is challenging because of the unpredictable therapeutic response and high bleeding risk in patients with active disease who are undergoing chemotherapy and who may experience thrombocytopenia and/or changes in renal or hepatic function and, according to the recent guidelines, it is limited to specific situations (i.e. severe renal insufficiency, AF associated with prosthetic mechanical valves and severe mitral stenosis). A careful evaluation of the antithrombotic strategy with the best efficacy/safety ratio (in terms of doses or drugs) is always needed in cancer patients and anticoagulation for CAT and AF should be tailored individually. An ongoing consultation of oncologists/hematologists with cardiologists and coagulation experts in a multidisciplinary approach, with a periodic re-assessment of the benefit/risk ratio of anticoagulation with changes in cancer status/advancement and treatment plans is needed.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"15 ","pages":"Article 100169"},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572724000117/pdfft?md5=51a5a3d162ae2f7db0b48f81a58d7779&pid=1-s2.0-S2666572724000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140407710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2024-03-08DOI: 10.1016/j.tru.2024.100165
Stephane Cormier , Deborah M. Siegal
{"title":"A framework for managing severe DOAC-related bleeding: Recognize, Reverse, Resume, Reduce","authors":"Stephane Cormier , Deborah M. Siegal","doi":"10.1016/j.tru.2024.100165","DOIUrl":"https://doi.org/10.1016/j.tru.2024.100165","url":null,"abstract":"<div><p>Bleeding is the main complication of treatment with anticoagulants, the most common adverse drug event that leads to emergency department visits, hospital admission, and death. While direct oral anticoagulants (DOACs) reduce the risk of major, fatal and intracranial bleeding compared to vitamin K antagonists, DOAC-associated bleeding is associated with substantial short-term mortality rates. To optimize management and improve outcomes, a standardized approach to managing severe bleeding includes rapid recognition, provision of treatments to reverse anticoagulation or enhance hemostasis, resumption of anticoagulation safety after bleed cessation and attention to secondary prevention measures and long-term monitoring. This narrative review outlines a pragmatic multimodal framework for severe DOAC bleed management with case examples to illustrate key principles.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"15 ","pages":"Article 100165"},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572724000075/pdfft?md5=af4da4d3b1e0ff9d9acdd3c5b9a6c55d&pid=1-s2.0-S2666572724000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2024-03-01DOI: 10.1016/j.tru.2024.100163
Jason Chung, Owais Mian, Ivan Stevic, Sajjad Afraz, Anthony Chan, Howard Chan, Bret M. Evers, Davide Matino
{"title":"Effects of prolonged tourniquet application on coagulation and fibrinolysis in rats","authors":"Jason Chung, Owais Mian, Ivan Stevic, Sajjad Afraz, Anthony Chan, Howard Chan, Bret M. Evers, Davide Matino","doi":"10.1016/j.tru.2024.100163","DOIUrl":"https://doi.org/10.1016/j.tru.2024.100163","url":null,"abstract":"","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"14 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572724000051/pdfft?md5=fc17a5a33f3cf3f297088c343cb4d52f&pid=1-s2.0-S2666572724000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140122979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2024-03-01DOI: 10.1016/j.tru.2023.100156
C. Doutrelon, W. Caré, P.-L. Conan, J.-M. Cournac, F. De Charry, C. Jacquier, S. Delamarre, M. Billhot, M. Aletti
{"title":"Long-term outcomes of COVID-19-associated pulmonary embolism: A French single-center retrospective study with one-year follow-up","authors":"C. Doutrelon, W. Caré, P.-L. Conan, J.-M. Cournac, F. De Charry, C. Jacquier, S. Delamarre, M. Billhot, M. Aletti","doi":"10.1016/j.tru.2023.100156","DOIUrl":"https://doi.org/10.1016/j.tru.2023.100156","url":null,"abstract":"","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"14 ","pages":"Article 100156"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572723000275/pdfft?md5=e7910515442e6f013101b510c657edf4&pid=1-s2.0-S2666572723000275-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombosis UpdatePub Date : 2024-03-01DOI: 10.1016/j.tru.2024.100159
Michael Wang , Hans-Jörg Hertfelder , Elyse Swallow , Alexandra Greatsinger , Emma Billmyer , Samson Fung , Peter L. Turecek , Hanna T. Gazda , Csaba Siffel
{"title":"Real-world treatment of patients with severe congenital protein C deficiency with protein C concentrate: A physician survey","authors":"Michael Wang , Hans-Jörg Hertfelder , Elyse Swallow , Alexandra Greatsinger , Emma Billmyer , Samson Fung , Peter L. Turecek , Hanna T. Gazda , Csaba Siffel","doi":"10.1016/j.tru.2024.100159","DOIUrl":"10.1016/j.tru.2024.100159","url":null,"abstract":"<div><h3>Introduction</h3><p>Replacement therapy with intravenous (IV) protein C concentrate (Ceprotin®; Baxalta US Inc., a Takeda company, Lexington, MA, USA; Takeda Manufacturing Austria AG, Vienna, Austria) is an approved treatment approach for patients with severe congenital protein C deficiency (SCPCD). Data on the real-world use of protein C concentrate are limited.</p></div><div><h3>Materials and methods</h3><p>In this non-interventional real-world study, physicians in Europe and the United States (US) with experience using protein C concentrate to treat patients with SCPCD completed an internet-based survey. Information collected included physician clinical practice details, experience treating patients with SCPCD, and opinions on the subcutaneous (SC) administration of protein C concentrate. Physicians responded based on their best recall.</p></div><div><h3>Results</h3><p>The analysis included 19 physicians (Europe, <em>n</em> = 12; US, <em>n</em> = 7) who had used protein C concentrate to treat 32 patients with SCPCD. Sixteen patients received IV long-term prophylaxis (LTP; treatment duration ≥3 months) and 12 received SC LTP. Five patients received both IV and SC LTP. Eighteen physicians indicated an interest in adding SC administration to the approved administration routes.</p></div><div><h3>Conclusion</h3><p>This survey shows that LTP with IV protein C concentrate is used in clinical practice by physicians in both Europe and the US for the treatment of patients with SCPCD<em>.</em> Protein C concentrate is also prescribed for SC administration by some physicians in Europe. Although only approved for IV administration, physicians in both Europe and the US indicated an interest in SC administration being an approved administration route for protein C concentrate.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"14 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572724000014/pdfft?md5=7eb60544e13e95919fa89f9395c9fae7&pid=1-s2.0-S2666572724000014-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139537182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}