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Keywords = cancer-associated venous thrombosis

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11 pages, 474 KB  
Article
Complications of Port-a-Cath Systems: An Institutional Study on Romanian Oncological Patients
by Adina Nemeș, Sebastian-Alexandru Pocol, Tunde Banciu and Diana Voskuil-Galoș
Cancers 2026, 18(1), 174; https://doi.org/10.3390/cancers18010174 - 5 Jan 2026
Viewed by 278
Abstract
Background: Rising cancer incidence and mortality have increased the use of central venous catheters (CVCs), including peripherally inserted central catheters (PICCs) and port-a-cath systems (PCSs), which play an important role in treatment administration. However, CVCs are associated with mechanical, infectious, and thrombotic [...] Read more.
Background: Rising cancer incidence and mortality have increased the use of central venous catheters (CVCs), including peripherally inserted central catheters (PICCs) and port-a-cath systems (PCSs), which play an important role in treatment administration. However, CVCs are associated with mechanical, infectious, and thrombotic complications. This study evaluates PCS-related complications and their management in oncological patients at The Oncology Institute “Prof. Dr. Ion Chiricuță,” Cluj-Napoca, Romania. Methods: This non-randomized, observational, retrospective study included cancer patients who had a PCS implanted at The Oncology Institute “Prof. Dr. Ion Chiricuță,” Cluj-Napoca, between 1 January 2024 and 31 December 2024 and were enrolled in a follow-up protocol to monitor and manage PCS-related complications. This study evaluated the incidence of complications, their association with predefined prognostic factors, and their management. Results: In the study cohort (n = 124 patients), complications related to the PCS were observed in 20% of the patients, with a mean interval to complication onset of 47 days. Early-onset complications were observed in 40% of patients, while the remaining 60% developed late-onset complications. PCS infection was the most common complication (10 patients), followed by wound dehiscence and thrombosis (6 patients each). Bleeding, extravasation, catheter migration, port malfunction, and torsion were each documented in a single patient. No prognostic factors were significantly associated with early or late PCS complications, with thrombosis approaching significance (p = 0.051). Conclusions: PCSs are generally safe in oncology patients; infections and thrombosis predominate as PCS-related complications, but rarely require removal, and standardized care enables long-term use, improving patient quality of life. Full article
(This article belongs to the Section Cancer Pathophysiology)
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18 pages, 1198 KB  
Article
Economic Evaluation of Direct Oral Anticoagulants Versus Low-Molecular Weight Heparin for Cancer-Associated Thrombosis in a Thai University-Affiliated Hospital
by Thanyarat Chaiwattanakowit, Nutnicha Pinitpracharome, Witoo Dilokthornsakul, Tananchai Akrawikrai and Piyameth Dilokthornsakul
J. Clin. Med. 2026, 15(1), 212; https://doi.org/10.3390/jcm15010212 - 27 Dec 2025
Viewed by 279
Abstract
Background/Objectives: Venous thromboembolism (VTE) is an important global health concern associated with considerable morbidity and mortality. Despite established guidelines for VTE treatment, there is a gap between clinical recommendations and their implementation in practice because of limited accessibility, particularly in low- and middle-income [...] Read more.
Background/Objectives: Venous thromboembolism (VTE) is an important global health concern associated with considerable morbidity and mortality. Despite established guidelines for VTE treatment, there is a gap between clinical recommendations and their implementation in practice because of limited accessibility, particularly in low- and middle-income countries and among patients with cancer. This study aimed to assess the cost-effectiveness of direct oral anticoagulants (DOACs) on VTE in patients with cancer at a Thai university-affiliated hospital. Methods: A cost–utility analysis using a Markov model was developed to estimate costs and quality-adjusted life-years (QALYs) of DOACs and low-molecular weight heparin (LWMH) in Thai patients with cancer aged over 60 years. The model with eight health states, including CAT on treatment, pulmonary embolism (PE), deep vein thrombosis (DVT), clinically relevant nonmajor bleeding (CRNMB), non-intracranial hemorrhage major bleeding (non-ICH MB), intracranial hemorrhage (ICH), off treatment, and any death, was developed with a one-month cycle length and used to estimate costs and health outcomes from a societal perspective with a lifetime horizon. The efficacy and safety of DOACs compared to LMWH were obtained from a network meta-analysis, while the costs were based on a Thai university hospital database. All costs and outcomes were discounted at 3%, and the Thai societal willingness-to-pay (WTP) threshold (THB 160,000 per QALY gained) was applied. The incremental cost-effectiveness ratio (ICER) was calculated to compare costs and QALYs of the interventions. Results: The total lifetime cost of LMWH was THB 70,928 (USD 2,163), while for apixaban, dabigatran, edoxaban, and rivaroxaban, the costs were THB 26,323 (USD 803), THB 33,667 (USD 1,027), THB 29,570 (USD 902), and THB 22,310 (USD 680), respectively. The QALYs for LMWH, apixaban, dabigatran, edoxaban, and rivaroxaban were 0.771, 0.775, 0.746, 0.759, and 0.770 QALYs, respectively. Compared to LMWH, apixaban provided 0.004 additional QALYs, with a decreased cost of THB 44,605 (USD 1,360), resulting in reduced expenses. On the other hand, dabigatran, edoxaban, and rivaroxaban were also associated with lower lifetime costs but reduced life-years and QALYs when compared with LMWH. Conclusions: This study revealed that apixaban is likely to be the preferred option for treating patients with CAT. However, policy decision-making process should take into account the uncertainties related to the implementation of this practice. Full article
(This article belongs to the Section Oncology)
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13 pages, 1302 KB  
Review
Venous Manifestations of Gastric Cancer: Bilateral Varicose Veins as a Rare Initial Presentation—A Narrative Review
by Anna Laura Maiozzi, Filomena Botta, Silvia Maccioni, Livia Stanga, Lucretia Marin-Bancila, Ciprian Ilie Rosca, Anca Dinu, Abhinav Sharma and Nilima Rajpal Kundnani
Gastrointest. Disord. 2025, 7(4), 70; https://doi.org/10.3390/gidisord7040070 - 31 Oct 2025
Viewed by 1225
Abstract
Background: Varicose veins (VVs) are an overlying manifestation of chronic venous disease, commonly occurring in the lower extremities. While typically linked to primary venous insufficiency, they can occasionally be secondary to systemic disease, e.g., malignancies, by various mechanisms such as tumor compression, hypercoagulability, [...] Read more.
Background: Varicose veins (VVs) are an overlying manifestation of chronic venous disease, commonly occurring in the lower extremities. While typically linked to primary venous insufficiency, they can occasionally be secondary to systemic disease, e.g., malignancies, by various mechanisms such as tumor compression, hypercoagulability, and paraneoplastic syndromes. Bilateral varicose veins, as a presenting symptom of gastric cancer, are extremely rare and poorly documented. Materials and Methods: A comprehensive literature search was conducted to identify reports and studies linking varicose veins and malignancies, with particular focus on gastric cancer. The search was performed using the PubMed, Scopus, and Web of Science databases covering the last 13 years. Results: Literature Review: A review of the literature in the past decade identified publications, mostly case reports, describing associations between varicose-like venous changes and malignancies such as gastric, pancreatic, hepatic, and small-bowel tumors. The predominant mechanisms reported were inferior vena cava obstruction, tumor-related thrombosis, and paraneoplastic migratory superficial thrombophlebitis (Trousseau’s syndrome). Only a few cases involved gastric cancer as the primary site, with venous changes often being the first clinical sign. There is limited experience with gastric cancer that presents alongside bilateral collateral or varicose veins initially. Apart from the various reports having malignancies and varicose veins we also describe the case of a 50-year-old man who had extended history of bilateral lower-limb varicose veins. Severe, unexplained anaemia without obvious bleeding was discovered during examination. A biopsy verified a gastric adenocarcinoma, while upper gastrointestinal endoscopy revealed an ulcerated mass on the stomach’s greater curvature. Peritoneal dissemination was discovered with additional staging. A palliative subtotal gastrectomy was carried out because of the patient’s ongoing anaemia and suspected chronic bleeding caused by the tumour. The venous symptoms preceded any gastrointestinal issues. Conclusions: Although uncommon, malignancy should be considered in the differential diagnosis for atypical or rapidly progressing bilateral varicose veins, especially when accompanied by systemic symptoms or lab results such as unexplained anemia. Increased suspicion may lead to earlier cancer detection in some patients. Full article
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14 pages, 268 KB  
Review
New Horizons in Venous Thromboembolism Management: A Narrative Review
by Wassim Bedrouni, Mahdi Bedrouni and James Douketis
J. Clin. Med. 2025, 14(21), 7668; https://doi.org/10.3390/jcm14217668 - 29 Oct 2025
Viewed by 1661
Abstract
Venous thromboembolism (VTE) remains a major cause of cardiovascular morbidity and mortality worldwide, and is a staple of daily clinical practice. While we have seen significant advancements in therapeutics over the last 20 years, several questions and controversies remain in the selection and [...] Read more.
Venous thromboembolism (VTE) remains a major cause of cardiovascular morbidity and mortality worldwide, and is a staple of daily clinical practice. While we have seen significant advancements in therapeutics over the last 20 years, several questions and controversies remain in the selection and duration of available therapies, as well as balancing the consequences of VTE and the bleeding risk imposed by treatment modalities. In recent years, new evidence based on randomized trials and registries have reshaped the therapeutic landscape. This narrative review synthesizes the latest advancements and future directions in VTE care, including recent guideline updates, new evidence pertaining to established pharmacologic therapy, risk stratification, interventional and procedural options, and special populations including the management of cancer-associated thrombosis, and the emerging promise of factor XI inhibition. In diagnostics, the field is moving beyond traditional methods with the investigation of novel biomarkers from proteomic and metabolomic studies and the clinical implementation of advanced imaging modalities like photon-counting CT, which offers superior resolution at lower radiation doses. Artificial intelligence is emerging as a transformative tool, potentially enhancing diagnostic accuracy in imaging. Ultimately, this review will assist clinicians in integrating evolving evidence with patient-centered decision-making to maximize benefit while minimizing harm and treating the diverse and common clinical problems of VTE. Full article
(This article belongs to the Special Issue Clinical Advances in Treatment for Venous Thromboembolism)
26 pages, 2844 KB  
Review
Clinical and Molecular Insights of Arterial and Venous Thrombosis in Myeloproliferative Diseases—Case-Based Narrative Review
by Anca Drăgan, Mădălina Găvănescu, Adrian Ştefan Drăgan, Alexandru Bardaş, Monica Dobrovie and Anca Doina Mateescu
Biomedicines 2025, 13(10), 2543; https://doi.org/10.3390/biomedicines13102543 - 18 Oct 2025
Viewed by 1969
Abstract
The myeloproliferative neoplasms (MPN), a heterogeneous group of disorders characterized by specific genetic mutations, have the development of arterial and venous thrombosis as their main complication. Almost 40–50% of MPN patients encountered arterial or venous thrombosis during the course of their disease. Moreover, [...] Read more.
The myeloproliferative neoplasms (MPN), a heterogeneous group of disorders characterized by specific genetic mutations, have the development of arterial and venous thrombosis as their main complication. Almost 40–50% of MPN patients encountered arterial or venous thrombosis during the course of their disease. Moreover, arterial thrombosis is linked to significant mortality, progression to myelofibrosis, and an increased risk of developing second cancers. Despite significant advancements in medical research, there are still unmet needs in this field. Our narrative review provides clinical and genetic insights into thrombosis associated with myeloproliferative neoplasms. We focus on the underlying pathophysiological processes, assessment methods, and risk stratification related to thrombotic events. This information aims to assist clinicians in accurately assessing the risks associated with MPN thrombosis, enabling a more personalized and effective approach to patient care. We based our review on a rare case of MPN-associated thrombosis, whose clinical presentation was marked by acute ischemia in both lower limbs. The thrombosis affected the distal aortic arch, thoracic and abdominal aorta, celiac trunk, common and proper hepatic arteries, proximal left renal artery, several segmental arteries in the right kidney, and the portal vein thrombosis. Our review presents various therapeutic options for these conditions. In the presented case, the multiple thrombi were treated medically, except for the popliteal artery thromboses, which required surgical management. This case may serve as a valuable reference for choosing treatment options for aortic and portal vein thrombosis, highlighting the multidisciplinary approach. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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11 pages, 243 KB  
Review
Next-Generation Anticoagulants: Precision Strategies for Patient-Centered Thromboprophylaxis
by Abdulrahman Nasiri, Manal Alshammari, Rawan Alqahtani, Omar Alshaer, Eysa Alsolamy, Hamad Alghethber and Reem Alkharras
J. Pers. Med. 2025, 15(10), 490; https://doi.org/10.3390/jpm15100490 - 14 Oct 2025
Viewed by 1529
Abstract
Thrombosis remains a leading preventable cause of global morbidity and mortality, with conditions like venous thromboembolism and atrial fibrillation affecting millions worldwide. Traditional anticoagulants (heparins, vitamin K antagonists) require careful monitoring due to narrow therapeutic windows. Direct oral anticoagulants (DOACs) greatly improved convenience [...] Read more.
Thrombosis remains a leading preventable cause of global morbidity and mortality, with conditions like venous thromboembolism and atrial fibrillation affecting millions worldwide. Traditional anticoagulants (heparins, vitamin K antagonists) require careful monitoring due to narrow therapeutic windows. Direct oral anticoagulants (DOACs) greatly improved convenience and reduced certain hemorrhagic complications (notably intracranial hemorrhage) compared to warfarin, but bleeding, drug–drug interactions, and unmet needs in special populations persist. This review highlights emerging strategies to decouple antithrombotic efficacy from bleeding risk. Novel agents targeting factor XI or XII (small molecules, antibodies, antisense oligonucleotides) have shown in early trials robust thromboembolism prevention with low bleeding. Advances in pharmacogenomics, biomarker-guided dosing, artificial intelligence risk prediction, and digital monitoring promise to personalize therapy. We discuss optimized approaches for high-risk subgroups (cancer-associated thrombosis, extremes of body weight, renal/hepatic dysfunction, pregnancy, perioperative care, and COVID-19) with citations to current evidence. Finally, we outline critical systems-level considerations, including drug accessibility, cost-effectiveness, and educational strategies, that are necessary to realize precision anticoagulation. Our synthesis is grounded in recent peer-reviewed literature and emphasizes innovations likely to improve safety and efficacy of thromboprophylaxis. Full article
(This article belongs to the Section Pharmacogenetics)
24 pages, 3057 KB  
Article
Venous Thrombogenesis and Cervical Cancer: Plasma MicroRNAs as Prognostic Indicators of Tumor Behavior
by Mariana Teixeira Costa, Beatriz Vieira Neto, José Brito da Silva, Luísa Carvalho, Lurdes Salgado, Deolinda Pereira, Filomena Adega, Valéria Tavares and Rui Medeiros
Int. J. Mol. Sci. 2025, 26(19), 9796; https://doi.org/10.3390/ijms26199796 - 8 Oct 2025
Cited by 2 | Viewed by 1078
Abstract
Cervical cancer (CC) is the fourth most common cancer among women globally, with venous thromboembolism (VTE) representing a life-threatening complication. Cancer-associated thrombosis (CAT) arises from tumor-driven activation of hemostasis, worsening prognosis. Recently, circulating microRNAs (miRNAs) have emerged as potential biomarkers for both CAT [...] Read more.
Cervical cancer (CC) is the fourth most common cancer among women globally, with venous thromboembolism (VTE) representing a life-threatening complication. Cancer-associated thrombosis (CAT) arises from tumor-driven activation of hemostasis, worsening prognosis. Recently, circulating microRNAs (miRNAs) have emerged as potential biomarkers for both CAT and cervical tumorigenesis. Thus, this study aimed to assess the implications of five miRNAs—miR-20a-5p, -23a-3p, -125b-5p, -145-5p, and -616-3p—in CC-related VTE context. These miRNAs were quantified by RT-qPCR in plasma from 69 CC patients before treatment. Briefly, VTE occurred in nine patients, decreasing overall survival (OS) [log-rank test, p = 0.005; hazard ratio (HR) = 4.78; 95% confidence interval (CI), 1.42–16.05]. Lower miR-20a-5p levels predicted VTE (ꭓ2 test, p = 0.027) and, in subgroup analyses, they were linked to cervical squamous cell carcinoma (CSCC) and older age (ꭓ2 test, p = 0.003 and p = 0.043, respectively). In VTE patients, miR-145-5p downregulation was associated with improved OS (log-rank test, p = 0.018), an effect also observed in the adenocarcinoma (ADC) subgroup (log-rank test, p = 0.039). The remaining miRNAs showed subtype-specific links to clinicopathological features and survival. These findings highlight the potential value of circulating miRNAs in thrombotic risk and prognosis assessment in CC. Full article
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19 pages, 1443 KB  
Article
The Presence of Neutrophil Extracellular Traps (NETs) in Brain Tumor Vessels Is Linked to Platelet Aggregates and Podoplanin in the Tumor Microenvironment
by Pegah Mir Seyed Nazari, Öykü Özer, Thomas Roetzer-Pejrimovsky, Maximilian J. Mair, Julia Riedl, Christine Brostjan, Anna Sophie Berghoff, Matthias Preusser, Johannes A. Hainfellner, Christine Marosi, Ingrid Pabinger and Cihan Ay
Cancers 2025, 17(19), 3141; https://doi.org/10.3390/cancers17193141 - 27 Sep 2025
Viewed by 1129
Abstract
Background: Multiple mechanisms might lead to cancer-related hypercoagulability. In brain tumors, podoplanin, via its ability to activate platelets, seems to play a crucial role in developing venous thromboembolism (VTE). Different stimuli (including activated platelets) can trigger the release of prothrombotic neutrophil extracellular [...] Read more.
Background: Multiple mechanisms might lead to cancer-related hypercoagulability. In brain tumors, podoplanin, via its ability to activate platelets, seems to play a crucial role in developing venous thromboembolism (VTE). Different stimuli (including activated platelets) can trigger the release of prothrombotic neutrophil extracellular traps (NETs) by neutrophils. It remains to be elucidated whether podoplanin-induced platelet aggregates might also impact NET formation and subsequent hypercoagulability and thrombosis. Methods: Patients with glioma were enrolled in this prospective observational cohort study. The primary endpoint was VTE. Immunohistochemical staining of NETs (via citrullinated histone H3 [H3Cit]) and neutrophils (via myeloperoxidase [MPO]) was conducted in glioma specimens and correlated with intravascular platelet clusters (via CD61) and podoplanin. Results: In total, 154 patients were included. H3Cit+ tumor vessels were found in 45/154 cases. H3Cit were significantly associated with increased intravascular platelet clusters (CD61− vs. CD61+ vs. CD61++ vs. CD61+++: 3.7% (1/27) vs. 18.6% (11/59) vs. 39.4% (13/33) vs. 57.1% (20/35), p < 0.001) and podoplanin expression (PDPN− vs. PDPN+: 14.3% (7/49) vs. 36.2% (38/105), p = 0.007) in the tumor tissue. Furthermore, H3Cit+ tumor vessels were significantly associated with tumor-infiltrating MPO+ neutrophils (H3Cit− vs. H3Cit+, median [Q1-Q3]: 6.0 [3.3–12.3] vs. 12.5 [5.9–22.0] cells/mm2, p < 0.001) and with D-dimer levels (H3Cit− vs. H3Cit+: 0.53 [0.32–1.10] vs. 0.84 [0.46–2.75] µg/mL, p = 0.034). The VTE risk was not linked to H3Cit+ tumor vessels (p = 0.613, log-rank). Conclusions: H3Cit in tumor vessels was not associated with VTE. However, H3Cit was linked to a local procoagulant phenotype in glioma, thereby potentially contributing to a systemic hypercoagulable state and thrombus formation. Full article
(This article belongs to the Section Tumor Microenvironment)
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14 pages, 540 KB  
Review
The Crucial Role of Tinzaparin in Managing Venous Thromboembolism in the Cancer Population
by Alfredo Mauriello, Adriana Correra, Anna Chiara Maratea, Celeste Fonderico, Arianna Amata, Vincenzo Quagliariello, Vincenzo Russo, Antonello D’Andrea and Nicola Maurea
J. Clin. Med. 2025, 14(19), 6695; https://doi.org/10.3390/jcm14196695 - 23 Sep 2025
Cited by 2 | Viewed by 1300
Abstract
Background: Venous thromboembolism (VTE) is a serious and common complication in cancer patients, and it is the second leading cause of death after cancer itself. Cancer-associated thrombosis (CAT) is an indicator of a poorer prognosis and can lead to treatment delays and increased [...] Read more.
Background: Venous thromboembolism (VTE) is a serious and common complication in cancer patients, and it is the second leading cause of death after cancer itself. Cancer-associated thrombosis (CAT) is an indicator of a poorer prognosis and can lead to treatment delays and increased healthcare costs. This review aims to provide a comprehensive update on the efficacy and safety of tinzaparin in the treatment and prophylaxis of VTE in cancer patients. Methods: This is a narrative review that examines the pharmacological properties of tinzaparin, as well as the results from clinical studies and meta-analyses. It includes a discussion of tinzaparin’s role in special patient populations and its comparison with other anticoagulants. Results: Tinzaparin is a low-molecular-weight heparin (LMWH) that does not accumulate in patients with renal insufficiency, eliminating the need for dose adjustments. Studies have shown that tinzaparin is a safe and effective treatment for CAT, with a favorable safety profile regarding hemorrhagic complications. In the CATCH study, tinzaparin showed a significant reduction in clinically relevant non-major bleeding compared to warfarin. Tinzaparin has also been shown to be more effective than vitamin K antagonists (VKAs) in promoting the recanalization of venous thrombi. A meta-analysis confirmed that tinzaparin was superior to VKAs in preventing VTE recurrence in the long term. Conclusions: While direct oral anticoagulants (DOACs) offer convenience, LMWHs like tinzaparin remain crucial, especially for patients with specific characteristics such as renal insufficiency, complex drug interactions, or a high risk of gastrointestinal bleeding. Tinzaparin’s favorable safety and efficacy, along with its unique pharmacological properties, make it a valuable option for managing VTE in the complex oncology population. Full article
(This article belongs to the Special Issue Managements of Venous Thromboembolism)
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19 pages, 348 KB  
Review
Venous Thromboembolic Events in Cancer Immunotherapy: A Narrative Review
by Cosmo Fowler and Stephen M. Pastores
J. Clin. Med. 2025, 14(14), 4926; https://doi.org/10.3390/jcm14144926 - 11 Jul 2025
Cited by 2 | Viewed by 2193
Abstract
Venous thromboembolism (VTE) represents a significant complication of cancer immunotherapy, with emerging evidence suggesting distinct pathophysiological mechanisms compared to traditional chemotherapy-associated thrombosis. This narrative review examines the epidemiology and pathogenesis of VTE in patients receiving immunotherapies for cancer including immune checkpoint inhibitors (ICIs), [...] Read more.
Venous thromboembolism (VTE) represents a significant complication of cancer immunotherapy, with emerging evidence suggesting distinct pathophysiological mechanisms compared to traditional chemotherapy-associated thrombosis. This narrative review examines the epidemiology and pathogenesis of VTE in patients receiving immunotherapies for cancer including immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, bispecific T-cell engagers (BiTEs), among others. Real-world studies demonstrate a wide range of VTE incidence rates in ICI recipients, with potential mechanisms including exacerbated underlying interleukin-8-mediated inflammatory pathways and consequent neutrophil extracellular trap (NET) formation. CAR T-cell therapy is associated with unique hemostatic challenges, including concurrent thrombotic and bleeding risks related to cytokine release syndrome. Current risk assessment tools show limited predictive utility in patients receiving immunotherapies for cancer, highlighting the need for novel stratification models. Future research priorities include developing immunotherapy-specific risk prediction tools, elucidating mechanistic pathways linking immune activation to thrombosis, and establishing evidence-based and tailored thromboprophylaxis strategies. As cancer immunotherapy continues to evolve, understanding and mitigating thrombotic complications remains crucial for optimizing patient outcomes. Full article
(This article belongs to the Special Issue Thrombosis: Latest Advances and Prospects)
16 pages, 857 KB  
Review
The Role of Tissue Factor-Positive Microparticles in Gynecological Cancer-Associated Disseminated Intravascular Coagulation: Molecular Mechanisms and Clinical Implications
by Muqaddas Qureshi, Muhammad Tanveer Alam and Ahsanullah Unar
Onco 2025, 5(3), 33; https://doi.org/10.3390/onco5030033 - 10 Jul 2025
Cited by 1 | Viewed by 2337
Abstract
Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF+ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles [...] Read more.
Gynecological malignancies (ovarian, endometrial, and cervical cancers), including disseminated intravascular coagulation (DIC), often provoke systemic coagulopathy. In recent years, tumor-derived, tissue factor–positive microparticles (TF+ MPs) have emerged as potent drivers of cancer-associated thrombosis and possibly DIC. These small (0.1–1 µm) membrane vesicles bud from cancer cell surfaces and carry procoagulant factors (phosphatidylserine and TF) on their surface. We review how TF+ MPs are generated by tumor cells and amplify the extrinsic coagulation cascade, potentially triggering DIC in patients with advanced gynecologic cancers. Clinical studies have linked el evated TF+ MP levels and activity to venous thromboembolism (VTE) in cancer, and small case series suggest dramatically high MP–TF activity in cancer-related DIC. We summarize evidence that TF+ MPs from ovarian tumors carry exceptionally high TF procoagulant activity (median ~80 pg/mL), and nearly all patients with cancer-associated VTE or DIC have MP–TF levels above normal. This review discusses diagnostic implications (e.g., measuring MP–TF activity as a biomarker) and treatment strategies (through the reduction in tumors, anticoagulation, and experimental TF inhibitors) in this setting. We also identify gaps in knowledge (standardized MP assays, prospective studies) and propose future directions (targeting MP formation or TF signaling). Two summary tables highlight recent studies of TF+ MPs in gynecologic cancer and their clinical outcomes. Illustrative figures depict the TF+ MP-triggered coagulation cascade and a conceptual framework for clinical management. Understanding TF+ MPs in gynecological cancer could improve the prediction and management of DIC and related thromboses. Full article
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13 pages, 260 KB  
Article
Extracellular Vesicles Profile and Risk of Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma
by Vladimir Otasevic, Charlotte Gran, Natasa Milic, Jelena Ivanovic, Sofija Kozarac, Vojin Vukovic, Biljana Mihaljevic, Nikolina Dukic, Jelena Vladicic Masic, Jawed Fareed, Jovan Antovic and Darko Antic
Int. J. Mol. Sci. 2025, 26(12), 5655; https://doi.org/10.3390/ijms26125655 - 12 Jun 2025
Viewed by 1597
Abstract
Thrombosis is a common complication in cancer patients, with a substantial impact on morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) and other aggressive lymphomas carry a high venous thromboembolism (VTE) risk. Extracellular vesicles (EVs) have gained attention in recent research as a [...] Read more.
Thrombosis is a common complication in cancer patients, with a substantial impact on morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) and other aggressive lymphomas carry a high venous thromboembolism (VTE) risk. Extracellular vesicles (EVs) have gained attention in recent research as a new potential biomarker for VTE development. To determine the profile and association of EVs with VTE in patients with DLBCL, we conducted a prospective cohort study on 62 patients diagnosed with DLBCL. A total of 11 patients (17.7%) developed VTE. The concentrations of platelet-derived EVs (PEVs), E-selectin+ EVs, P-selectin+ EVs, tissue factor (TF)-positive/CD20+ EVs, TF−/CD19+ EVs, TF−/CD45+ EVs, and TF−/CD20+ EVs were significantly higher in DLBCL patients compared to healthy controls. In contrast, the concentration of TF− PEVs was significantly lower in DLBCL patients compared to healthy controls. No statistically significant differences were observed in the concentrations of the EV profiles among the DLBCL patients with and without VTE. Using Cox regression analysis, we found that none of the observed EV populations demonstrated an association with overall survival (OS). In conclusion, patients with DLBCL have elevated concentrations of distinct EV populations—in particular, PEVs, E-selectin EVs, P-selectin EVs, TF+/CD20+ EVs, and TF− DLBCL/B-cell EVs (CD19, CD20, CD45)—compared to healthy controls. DLBCL patients exhibit a specific EV profile, which is not significantly related to the risk of VTE and OS outcomes. Our data provide an intriguing insight into EV profiles in patients with DLBCL. Additional research is needed to elucidate these findings further. Full article
25 pages, 781 KB  
Review
Exploring the Emerging Association Between Immune Checkpoint Inhibitors and Thrombosis
by Hassan Fawaz, Hasan Numan, Mohamad Hadi El Charif, Nicole Charbel, Sacha El Khoury, Joe Rizkallah, Amal El Masri, Arafat Tfayli and Firas Kreidieh
J. Clin. Med. 2025, 14(10), 3451; https://doi.org/10.3390/jcm14103451 - 15 May 2025
Cited by 2 | Viewed by 3007
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their association with thrombosis presents significant clinical challenges. Patients with cancer already exhibit elevated risks for venous thromboembolism and arterial thrombosis, with treatment modalities like chemotherapy further exacerbating this risk. Emerging evidence suggests that [...] Read more.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their association with thrombosis presents significant clinical challenges. Patients with cancer already exhibit elevated risks for venous thromboembolism and arterial thrombosis, with treatment modalities like chemotherapy further exacerbating this risk. Emerging evidence suggests that ICIs contribute to thrombotic events through multifactorial mechanisms, including immune dysregulation, T cell activation, endothelial dysfunction, elevated tissue factor expression, and impaired fibrinolysis. Additional risk factors such as obesity, smoking, prior thrombotic events, and combination ICI therapy further increase thrombosis susceptibility. The literature reports varying incidence rates of ICI-associated thrombosis, with some studies indicating comparable risks to chemotherapy, while others highlight higher rates, particularly during the initial treatment phase. Management aligns with standard protocols for cancer-associated thrombosis, using low-molecular-weight heparin or direct oral anticoagulants, though optimal treatment duration and the role of prophylactic anticoagulation require further investigation. This review provides a comprehensive overview of the mechanisms, incidence rates, and clinical management strategies of ICI-associated thrombosis, emphasizing the importance of proactive risk assessment to optimize patient outcomes. Full article
(This article belongs to the Section Vascular Medicine)
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30 pages, 3837 KB  
Review
Challenges and Opportunities of Direct Oral Anticoagulant (DOAC) Therapy in Complex Clinical Scenarios: A Comprehensive Review and Practical Guide
by Giuseppe Miceli, Anna Maria Ciaccio and Antonino Tuttolomondo
J. Clin. Med. 2025, 14(9), 2914; https://doi.org/10.3390/jcm14092914 - 23 Apr 2025
Cited by 6 | Viewed by 14214
Abstract
Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant [...] Read more.
Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations. Full article
(This article belongs to the Special Issue Thromboembolic Disease and Antithrombotic Therapy)
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13 pages, 2419 KB  
Review
Prevention of Peripherally Inserted Central Catheter (PICC)-Associated Vein Thrombosis in Cancer: A Narrative Review
by Agnese Maria Fioretti, Pietro Scicchitano, Daniele La Forgia, Raffaele De Luca, Elena Campello, Carlo Gabriele Tocchetti, Marcello Di Nisio and Stefano Oliva
Biomedicines 2025, 13(4), 786; https://doi.org/10.3390/biomedicines13040786 - 24 Mar 2025
Cited by 6 | Viewed by 5100
Abstract
Venous thromboembolism (VTE) is considered the most common and potentially life-threatening cardiovascular complication in cancer and the second leading cause of death after cancer progression itself. In recent years, the steadily increasing rate of cancer-associated thrombosis (CAT) seems mainly related to amelioration in [...] Read more.
Venous thromboembolism (VTE) is considered the most common and potentially life-threatening cardiovascular complication in cancer and the second leading cause of death after cancer progression itself. In recent years, the steadily increasing rate of cancer-associated thrombosis (CAT) seems mainly related to amelioration in imaging techniques and the placements of central venous catheters (CVCs). The pivotal role of CVCs in the switch from hospital to home care is offset by its high thrombotic burden. The peripherally inserted central catheter (PICC) offers advantages (convenience, fast access, and cost-effectiveness) in comparison to centrally inserted devices (PORT), but increased thrombotic risk is reported. The aim of this narrative review was to offer a comprehensive overview of the existing literature about PICC-related thrombosis (PICC-VTE) by analyzing the current knowledge and related gaps. We further discussed advancements in insertion techniques, underscored the role of the novel PICC-PORT lines, and provided a “head-to-head” comparison among major guidelines on primary thromboprophylaxis. Full article
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