Hypertriglyceridemia and cerebral venous thrombosis are well-recognized complications of asparaginase therapy for B-cell acute lymphoblastic leukemia. Hypertriglyceridemia has also been associated with an increased risk of thrombosis in conditions such as Behçet’s disease and has been implicated in a pediatric case of cerebral venous thrombosis, suggesting a possible link between hypertriglyceridemia and cerebral venous thrombosis. We present the case of a patient with acute delirium and amnesia, revealing a venous infarction caused by cerebral venous thrombosis of the sinus rectus. Classical causes, including hereditary thrombophilia, were excluded. Notably, the patient’s blood appeared lactescent at admission, and laboratory testing revealed severe hypertriglyceridemia. The patient improved significantly with heparin, dietary modifications, and ciprofibrate. This case suggests that severe hypertriglyceridemia should be considered as a potential trigger of cerebral venous thrombosis and that including a lipid panel in cerebral venous thrombosis work-ups could be considered, allowing subsequent specific therapeutic interventions.
Background: Direct oral anticoagulants (DOACs) are largely prescribed, and the lack of need for a laboratory monitoring was the main reason for their large diffusion. However, a wide inter-individual variability has been described, and the need for blood levels measurement when a thrombotic or hemorrhagic event occurred has been suggested. Materials and methods: In 2022, a survey was conducted among the Italian centers affiliated with the Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies - FCSA, recording that only few centers provided DOACs testing. In 2025, a second survey was performed to evaluate if a change in that area have occurred. Results: We observed a rapid increase in the number of centers providing DOAC testing, from 39/124 (31.0%) in 2022 to 72/122 (59.0%) in 2025; 26% of centers not providing DOAC testing, claimed no funding for testing. In 70/72 (97.2%) of centers, DOAC testing was limited to selected conditions, such as thrombotic or hemorrhagic complications. Conclusions: Data derived from our survey are relevant in developing adequate anticoagulation stewardship programs, that are increasingly required.
Patients with cancer have increased risk of venous thromboembolism (VTE), contributing to excess morbidity, mortality, treatment delays, and healthcare utilization. The incidence of cancer associated VTE has increased over the past two decades. Patients with malignancy now comprise approximately 20% of the global VTE burden. VTE risk is highest during the first 3-6 months after a new or recurrent cancer diagnosis. A new diagnosis of VTE can herald the presence of cancer. Although the risk declines over time it does not return to baseline for up to two years after completing cancer treatment in those with no evidence of disease. Randomized trials of prophylactic-dose anticoagulation for primary VTE prevention in ambulatory patients with cancer, including the direct oral anticoagulants, demonstrate a 35-60% reduction in VTE events, however, routine use of primary prophylaxis remains quite limited among patients with cancer due to excessive bleeding risks which are doubled with most anticoagulants. These competing risks are reflected in conditional guideline recommendations from major societies which suggest consideration of prophylaxis only in selected high-risk patients with concomitantly low bleeding risks. By contrast, in the general population, statin therapy has been shown to reduce VTE rates by 30 to 40% with no increase in hemorrhage and thus might be a highly effective intervention to reduce the risk of cancer associated thrombosis. The Statin Therapy to Prevent Cancer Associated VTE (STAT-CAT) trial, funded by the NHLBI, has been designed to directly test this hypothesis among 4,000 patients initiating cancer therapy. This review summarizes emerging evidence supporting statins as a potential approach to primary VTE prevention in patients with cancer and reviews clinical trials addressing statins for VTE risk reduction.
Patients with cancer have an increased risk of thrombosis requiring anticoagulation. Direct oral anticoagulants have become the primary anticoagulant of choice in most patients with cancer. Patients with cancer also receive many concomitant medications including anticancer therapies with potential risks of drug-drug interactions with anticoagulants that can lead to concerns of bleeding or recurrent thrombosis. The best management strategies remain unclear. In this article, we aim to review the available literature pertaining to pharmacokinetic interactions between anticancer therapies and direct oral anticoagulants and provide guidance based on the evidence.
Background: Gene therapy offers a transformative treatment option for hemophilia A (HA) by restoring endogenous factor VIII production. Shared decision-making (SDM) is a collaborative process that allows patients and clinicians to weigh the risks and benefits of complex treatment options such as gene therapy. However, no SDM tools exist for the specific needs of Italian persons with HA. Materials and Methods: An Expert Advisory Board comprising nine experts (including hematologists, a psychologist, a methodology expert, a linguist and patient advocacy group representatives) met three times between March and July 2024 to discuss gene therapy for HA in Italy, and develop an SDM tool to determine the suitability of gene therapy for HA. Results: The resulting modular SDM tool allows for structured interactions between clinicians and patients, while remaining sensitive to each patient’s level of readiness and understanding. The tool includes three components: Role Definition, Agenda Alignment, and Intention Setting, with supporting materials to guide patient-clinician dialogue and various resources (questionnaires, brochures, and visual aids). Conclusions: Despite requiring confirmation in further studies, this SDM tool may represent a useful component of patient-centered care for HA in the Italian healthcare setting.
A few years ago, an article in the first issue of Bleeding, Thrombosis and Vascular Biology, argued that biomedical research should move beyond the mechanical use of the p-value. That message was not new, but it was timely. It remains timely today. The p-value is still often treated as a gatekeeper: below 0.05, a finding is “real”; above 0.05, it is “negative”. This habit is simple, familiar, and convenient. It is also misleading [...]
Dear Editor, Anyone who has known Prof. Gian Franco Gensini and has had the opportunity to interact with him, in the professional field or even in social life, must have been fascinated by his forward-looking vision of the future and by his constructive optimism [...].
Prediction of cancer-associated thrombosis (CAT) remains a major clinical challenge. Although genomic data and clinic-genetic scores have advanced understanding, they do not explain all inter-individual variability in CAT risk. Non-genomic omics, including proteomics, transcriptomics and epigenomics, capture complementary, dynamic biological information that can improve risk stratification. In summary, genomics contributes one piece of a much larger puzzle, necessary, informative, but fundamentally insufficient when used alone to understand, predict or manage CAT. This review synthesizes recent evidence on these non-genomic–omics for CAT prediction, highlights current limitations (validation, standardization, causal inference) and outlines priorities for translational development and clinical validation.
This study explores the crucial role of abnormal O- and N-glycosylation (modification of sugar molecules attached to proteins) in cancer progression and metastatic spread. It examines the effect of this deregulation at several stages of tumor development: primary tumor, microenvironment, blood circulation, and extravasation. During most of these stages, cancer cells can interact with platelets. Platelets are no longer simply coagulation agents but entities capable of educating cancer cells by modifying their enzymatic and transcriptional landscape. The possible use of a specific glycoprotein as a biomarker and a glycan common to several cancers as a therapeutic target has also been described.
This review examines the complex relationship between hormonal signaling, cancer biology, and thrombosis, focusing primarily on cancer-associated venous thromboembolism (VTE) in hormone-sensitive malignancies. Hormones regulate key hemostatic processes—including coagulation, platelet activity, endothelial function, and fibrinolysis—and disturbances in these pathways can promote thrombotic complications in patients with cancer. Sex hormones play distinct roles in modulating thrombotic risk. Estrogens tend to promote a prothrombotic state by increasing procoagulant factors and reducing anticoagulant activity, whereas progesterone has minimal direct hemostatic effects. The impact of testosterone remains less clear, although some data suggest a transient increase in VTE risk shortly after initiation of testosterone therapy. In hormone-dependent cancers, endocrine therapies further modify thrombotic risk through their effects on hormonal pathways and tumor-associated inflammation. The magnitude and mechanisms of thrombosis vary across malignancies. In breast cancer, VTE risk is generally moderate but increases with age, obesity, disease stage, chemotherapy, and particularly endocrine therapy such as tamoxifen, which is associated with a two- to three-fold higher VTE risk. Ovarian cancer is among the most thrombogenic solid tumors, driven by tumor biology, inflammatory activation, and intensive treatments such as surgery and platinum-based chemotherapy. Endometrial cancer risk is linked to prolonged estrogen exposure and obesity, while prostate cancer demonstrates increased thrombotic risk primarily related to androgen deprivation therapy, which induces metabolic and vascular changes that favor hypercoagulability. These sex-specific differences highlight the need for risk-adapted strategies for thromboprophylaxis and surveillance. Clinical management should consider tumor type, hormonal environment, treatment modality, and patient-specific risk factors. As survival improves in hormone-sensitive cancers, optimizing prevention of thrombotic complications while minimizing bleeding risk represents an important component of personalized oncologic care. Graphical Abstract
Glioblastoma (GBM) is an aggressive, treatment-resistant brain tumor. Elevated platelet counts are associated with tumor growth, and platelets accumulate in GBM tumors. Our study found that cyclooxygenase (COX)-2 expression and prostaglandin (PG)E₂ biosynthesis increase during the formation of U-87MG GBM cell spheroids. The COX-2 inhibitors celecoxib and rofecoxib inhibited PGE2 biosynthesis and reduced U-87MG spheroid growth. In cocultures of platelets with U-87MG spheroids, enhanced thromboxane (TX)B₂ was reduced by the selective exposure of platelets to aspirin, suggesting a platelet origin. In U-87MG cells, platelets increased the expression of COX-2 and epithelial-mesenchymal transition (EMT) marker genes. We prevented these effects by pretreating platelets with aspirin to inhibit TXA2 biosynthesis or with a TXA2 receptor antagonist. A TXA2 mimetic stimulated the expression of both COX-2 and epithelial-mesenchymal transition (EMT) markers in spheroids. Altogether, these findings indicate that platelet TXA2 induces COX-2 and promotes EMT in U-87MG cells. Aspirin, by inhibiting platelet TXA2, could contribute to reduced tumor growth and invasion in GBM.
Cancer-associated thrombosis (CAT) is an umbrella term describing multiple forms of deregulated hemostasis and clotting related to cancer progression or therapy. Venous thromboembolism (VTE) is the most prevalent and widely studied systemic manifestation of CAT associated with considerable morbidity and risk of life-threatening pulmonary embolism (PE). While some aspects of CAT may be unspecific or iatrogenic, the biology of cancer cells contributes to this condition through the expression of the procoagulant phenotype, often attributable to upstream oncogenic mutations, the state of the epigenome, and influences of the tumor microenvironment (TME). High-grade astrocytic brain tumors (HGGs) are among the most procoagulant neoplastic disease states. Podoplanin (PDPN) and tissue factor (TF) have been implicated in HGG-associated VTE risk, while isocitrate dehydrogenase (IDH) mutations protect from thrombosis in HGG. Highly procoagulant, IDH-wild-type HGGs, such as glioblastoma (GBM), represent a cluster of disease states, each comprising cellular populations endowed with different repertoires of TF and PDPN expression. GBM cells project their influence systemically, at least in part, through the release of extracellular vesicles (EVs) carrying TF, PDPN, and other factors. The specific roles of these mechanisms in GBM-associated VTE are under investigation. Given the intense interest in developing new treatment strategies in GBM, the interplay between these interventions and the activity of the hemostatic system is of paramount importance. Indeed, a better understanding of mechanisms driving CAT in molecular and therapeutic contexts of specific brain tumor subtypes could inform more individualized approaches to management of thrombosis in patients.
Anti-angiogenic therapies, including agents targeting vascular endothelial growth factor or its receptors are widely used for the treatment of different types of cancer. On-target adverse events of anti-angiogenic therapies include an increased risk of bleeding due to impaired endothelial integrity and vascular regeneration. In addition, an increased risk of arterial and venous thromboembolic events has been reported for selected anti-angiogenic agents. Anticoagulation therapy, either due to pre-existing indications or for the treatment of thromboembolic events during anti-angiogenic treatment, therefore, poses a clinical challenge. In the absence of robust evidence-based guidelines and in the context of heterogeneous patient- and treatment-related risk factors, individualized assessment of both thromboembolic and bleeding risk is warranted. High-quality evidence to support clinical management in this setting remains scarce, necessitating personalized risk-benefit evaluations. In the present narrative review, we summarize available data on the risk profiles of thromboembolic and bleeding events associated with different anti-angiogenic therapies and discuss strategies for anticoagulation management in this setting.
Despite strong evidence and professional society recommendations for interventions to reduce cancer-associated thrombosis, uptake in clinical practice remains low. Implementation science offers structured approaches to close this evidence-to-practice gap. Frameworks such as the Implementation Research Logic Model and Consolidated Framework for Implementation Research guide identification of barriers, selection of strategies to address the barriers, and evaluation of clinical and implementation outcomes. Herein, the application of implementation science to close the gap between evidence for cancer-associated thrombosis prevention and use in clinical practice is discussed. Multi-level strategies, including clinician and patient education and electronic health record decision support, are essential to improve adoption. Clinical programs such as the Vermont Model demonstrate feasibility but highlight challenges in sustainability and scale-up. Integrating recommended cancer-associated prevention interventions into routine oncology care through tailored implementation strategies can reduce preventable morbidity and mortality, improving outcomes for patients with cancer.
Splanchnic vein thrombosis (SVT), including portal, splenic, and mesenteric vein thrombosis and the Budd–Chiari syndrome, is an uncommon manifestation of venous thromboembolism frequently associated with solid abdominal malignancies and myeloproliferative neoplasms (MPNs). The management of cancer-associated SVT is challenging due to heterogeneous clinical presentations, competing risks of thrombosis and bleeding, and the lack of high-quality clinical studies in this setting. Based on available evidence, anticoagulation is associated with higher rates of recanalization in patients with solid cancer, with no impact on the mortality rates and a non-negligible bleeding risk. Most available data derive from observational studies, with low-molecular-weight heparin (LMWH) historically representing the most frequently used anticoagulant, although direct oral anticoagulants (DOACs) are increasingly prescribed following evidence from cancer-associated thrombosis in usual sites. In MPN-associated SVT, anticoagulation is generally recommended indefinitely in combination with cytoreductive therapy. Available cohort studies suggest comparable outcomes among vitamin K antagonists (VKAs), LMWH, and DOACs, but robust comparative data are lacking. Overall, current evidence supports an individualized, risk-adapted anticoagulant approach in patients with cancer-associated SVT.
Venous thromboembolism (VTE) is an important cause of morbidity and mortality in individuals with active cancer. Most cancer-associated VTE occurs in the ambulatory setting in individuals receiving systemic therapy. Multiple anticoagulants are currently available for the treatment of cancer-associated VTE; a major drawback is the risk of bleeding. No drugs are currently approved for primary prevention of VTE in cancer in the outpatient setting. Adherence/compliance issues, drug-drug interactions, and concern about renal and hepatic metabolism are other ongoing concerns with these agents. Thus, there are major unmet needs in the quest to optimize the treatment and prevention of VTE in cancer. Factor XI (FXI) has only a small impact on hemostasis but contributes significantly to thrombosis. It is therefore a potential therapeutic target with less concern for enhancing bleeding. Several early-phase studies suggest that FXI inhibitors have reduced the risk of bleeding at therapeutic doses in the prevention of venous and arterial events in cardiology and postoperative settings. Multiple studies are now addressing the utility of this new class of drugs in cancer-associated VTE, including completed, ongoing, and planned trials of primary prevention and treatment. This narrative review addresses the role of FXI in thrombosis, the rationale for FXI inhibitors in primary and secondary prevention settings in malignancy and provides an overview of preliminary results and future directions.
Apart from cancer progression itself, cancer-associated thrombosis (CAT) is the second leading cause of death among cancer patients. However, the mechanisms underlying CAT remain incompletely understood. Traditional animal models cannot fully reproduce the complex pathophysiological process of CAT in humans. Meanwhile, existing clinical prediction models are still insufficient to provide reliable risk prediction tools for venous thromboembolism (VTE) in cancer patients. With the accelerating development of microfluidics technology, it has become possible to construct thrombotic microenvironments with high physiological relevance in vitro, providing a new platform for the study of CAT. In this review, we summarized the contributions and limitations of animal models and clinical studies to CAT, and highlighted a series of artificial vascular microfluidics developed by our research group in recent years that can, to some extent, simulate the in vivo microenvironment for CAT. Based on this microfluidics platform, we conducted thrombin generation analysis to explore the potential mechanisms of cancer-related thrombosis and predict VTE risk in cancer patients. Finally, we further discuss the key issues and the challenges in the future. Graphical Abstract
Cancer-associated thrombosis is a major contributor to morbidity and mortality among patients with cancer, significantly impacting both treatment strategies and the overall quality of life for these patients. The pathogenesis of thrombosis in cancer is multifactorial, involving intricate interactions between both host immune responses and tumor-derived factors. This review highlights several key immune-thrombotic pathways implicated in the development of cancer-associated thrombosis, including neutrophil activation and NETosis, monocyte/macrophage-mediated coagulation, and tumor-induced endothelial activation via inflammatory cytokines. A more profound understanding of these mechanisms is essential for refining risk stratification, developing targeted prophylactic strategies, and improving therapeutic management of cancer-associated thrombosis.
Cancer is accompanied with significant changes in hemostasis caused by both the underlying malignancy and its treatment, which increases the risk of thrombotic and bleeding consequences. While cancer-related thrombosis has been extensively studied, bleeding remains relatively unexplored, despite its major contribution to morbidity and mortality in this population. The epidemiology of bleeding in cancer patients is complicated and difficult to assess. Multiple linked factors influence risk, such as tumor kind, disease stage, treatment modalities, patient clinical context, and concomitant diseases. Furthermore, bleeding risk varies over time, reflecting dynamic changes in tumor load, treatment approaches, and host variables. As a result, estimates of incidence and prevalence vary greatly depending on the population investigated, the date of cancer diagnosis, and the bleeding definitions used. The type and dosage of anticoagulant medication may also influence this risk. These problems underline the importance of a more holistic approach to bleeding in cancer care. Bleeding prevention should be prioritized in future cancer-related venous thromboembolism management regimens. To lower the clinical burden of cancer and enhance patient outcomes, we must advance our understanding of bleeding epidemiology.
