Thrombosis and haemostasis最新文献

The advent of angiogenesis inhibitors has expanded therapeutic options for tumors but poses challenges due to bleeding risks, especially in patients requiring anticoagulation therapy for cancer-associated hypercoagulability.This study aimed to evaluate whether combining anticoagulants with angiogenesis inhibitors increases bleeding risk in cancer patients.A network meta-analysis was conducted based on PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials to compare bleeding risks with angiogenesis inhibitors alone versus their combination with anticoagulants. Furthermore, a real-world cohort of 645 patients receiving antiangiogenic therapies between January 2010 and June 2024 was studied. Patients were separated into two groups according to whether they were receiving concomitant anticoagulants. The primary outcome was all-grade bleeding events.Of 2,644 patients from six studies included in network meta-analysis, all-grade bleeding events were found in 614 (23.2%) patients. The addition of anticoagulation to either high-dose bevacizumab (10 or 15 mg/kg) (OR 4.95, 95% CI: 2.68-9.42) or antiangiogenic tyrosine kinase inhibitors (OR 2.2, 95% CI: 1.08-4.44) significantly increased bleeding risk compared with antiangiogenic monotherapy, except for low-dose bevacizumab (5 or 7.5 mg/kg). In the cohort study, 163 patients matched in each group after propensity score matching weighting. Over a median follow-up duration of 56 days, there were 28 (17.2%) all-grade bleeding events during concurrent treatment and 16 (9.8%) all-grade bleeding events reported during antiangiogenic monotherapy.Adding anticoagulation to high-dose bevacizumab or antiangiogenic TKIs might increase bleeding risk compared with monotherapy. Conversely, anticoagulants appeared to be safe in patients receiving low-dose bevacizumab.

Acute myocardial infarction (AMI) remains a formidable challenge in cardiovascular medicine, necessitating effective antiplatelet therapy to mitigate adverse outcomes. Recent advances have underscored the pivotal role of oxidative stress and micro ribonucleic acids (miRNAs) in regulating platelet activation and modulating the efficacy of antiplatelet agents. This review comprehensively examines the current understanding of how oxidative stress influences platelet function and the regulatory mechanisms of miRNAs in this context. It discusses the dual role of oxidative stress in promoting and impairing platelet activity and its implications for miRNAs as critical modulators of platelet activation, including their potential utility as biomarkers and therapeutic targets. Furthermore, the interaction between oxidative stress, miRNA expression, and antiplatelet drugs is analyzed to elucidate their combined impact on AMI treatment. These insights provide potential pathways to optimize therapeutic strategies, ultimately improving patient outcomes in AMI management.

Cancer-associated thrombosis (CAT) is common and a leading cause of mortality in patients with cancer. In specific CAT scenarios, low-molecular-weight heparins (LMWHs), including tinzaparin, are preferred over direct oral anticoagulants. Despite the importance of understanding LMWH pharmacokinetics (PK) in cancer for optimizing CAT management, available data remain limited.To compare tinzaparin PK in cancer and non-cancer patients by developing a population PK model.This prospective, multicenter, case-: control trial enrolled patients receiving once-daily subcutaneous tinzaparin at a therapeutic dose of 175 IU·kg^-1, including matched cancer and non-cancer patients. Plasma anti-Xa activity was measured at multiple time points and analyzed using a non-linear mixed-effect modeling. A PK model was developed, and covariate effects were assessed for parameters of the model. The impact of cancer on tinzaparin PK was evaluated by incorporating cancer status as a categorical covariate.A total of 333 patients (including 46 matched cancer and non-cancer patients) were included in the analysis. A monocompartmental model with first-order absorption best described tinzaparin PK. The volume of distribution was associated with body weight, while clearance and anti-Xa activity were associated with creatinine clearance. No significant differences were observed between matched cancer and non-cancer patients in anti-Xa activity exposure at day 1 and steady state.PK profiles were comparable between cancer and non-cancer patients. Additionally, further studies should clarify the role of renal function in guiding tinzaparin dosing.

Vaccination against SARS-CoV-2 was instrumental in controlling the COVID-19 pandemic. Rare cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) emerged following vaccination with the adenovirus vector-based vaccines ChAdOx1 nCov-19-S and Ad26.COV2.S. VITT is mediated by high-titer IgG anti-platelet factor 4 (PF4) antibodies that activate platelets, leading to thrombosis and thrombocytopenia. Similar antibodies have been detected following natural adenovirus infections, suggesting a common immunological trigger. This indicates that a constituent of adenovirus is relevant. Adenovirus is a DNA virus. Virion-unbound viral DNA is present in natural adenovirus infections.To identify whether free virion-unbound DNA is present in ChAdOx1-nCoV19 vaccine and whether adenoviral DNA enhances the immune response to PF4 in mice.We assessed ChAdOx1 nCov-19-S for virion-unbound DNA and differentiated free human and free adenovirus DNA by sequencing. We immunized mice with ChAdOx1 nCov-19-S and its fractions, in which we removed proteins by proteinase K and/or DNA by DENERASE.Using ultracentrifugation and proteinase K digestion, we isolated and characterized free nucleic acids, confirming the presence of both adenoviral and host cell-derived DNA in ChAdOx1 nCov-19-S. Mice immunized with PF4 in combination with ChAdOx1 nCov-19-S or its virion-free supernatant-but not with PF4 alone-developed a strong anti-PF4 IgG response, an effect completely abolished by nuclease (DENARASE) treatment.Virion-unbound DNA in ChAdOx1 nCov-19-S contributes to anti-PF4 antibody formation. This highlights the potential of reducing virion-unbound DNA in vaccine formulations to mitigate unintended immune responses to PF4.

Heavy menstrual bleeding (HMB) is a common complication of anticoagulant therapy in menstruating women with venous thromboembolism (VTE). Direct oral anticoagulants (DOAC) used for VTE treatment may differ in their menstrual bleeding profiles. Therefore, the prospective multicenter noninterventional investigator-initiated HEMBLED registry (HE: avy M: enstrual BLE: eding in patients treated with D: OAC) was performed to analyze spontaneous menstrual bleeding in women treated with therapeutic DOAC doses.A modified pictorial blood assessment chart (PBAC) score was used to define the severity of menstrual bleeding. Patients were only included when they did not use hormonal or intrauterine contraception methods. The prospective follow-up was 4 months. The primary endpoint was the comparison of the PBAC scores between the individual DOAC groups.Overall, 73 patients with 213 monthly assessments of the PBAC scores were analyzed. Patients were on average 35 years old and were anticoagulated with apixaban (62%), rivaroxaban (26%), edoxaban (7%), or dabigatran (6%). The PBAC scores of the rivaroxaban group (mean: 145 points) were significantly increased by 54% compared with the apixaban group (mean: 93 points, p = 0.0193). HMB (PBAC score > 100 points) at least once was detected in 53% of the apixaban group compared with 79% of the rivaroxaban group (p = 0.0913). The duration of menstrual bleeding was numerically shorter in the apixaban group compared with the rivaroxaban group (p = 0.1894).DOAC differ in their influence on the intensity of spontaneous menstrual bleeding. This should be taken into account when advising young women with VTE who need an oral anticoagulant.

Ankylosing spondylitis (AnkS) has been associated with an increased risk of venous thromboembolism (VTE). Data comparing VTE events in AnkS with other immune-mediated inflammatory diseases and non-inflammatory patients are lacking. This study aimed to compare clinical outcomes between VTE patients with AnkS, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and patients without inflammatory disease.We analyzed 112,539 VTE patients enrolled in the RIETE registry. A Greedy Nearest Neighbor Matching approach was used to select a comparable non-inflammatory VTE cohort. Outcomes included recurrent VTE, mortality, and major bleeding at 1 year, and were compared using Cox regression or sub-hazard models.Among the inflammatory-disease cohort of 2,427 VTE patients (mean age ± standard deviation, 64.1 ± 16 years, 41.4% males), 6.4% had AnkS, 50.6% had RA, 10.8% had SLE, and 32.2% had IBD. The matched population without inflammatory disease comprised 7,800 VTE patients. The rate of recurrent VTE was 11.5%, all-cause mortality 5.1%, and major bleeding 1.9% in AnkS patients. Similar rates were observed in patients with RA, SLE, or IBD. Recurrent VTE was significantly higher in AnkS patients than in the non-inflammatory group (HR, 7.43, 95% CI, 2.28-24.23). AnkS patients who discontinued anticoagulation earlier than 1 year experienced higher adverse outcomes (a composite of mortality, major bleeding, recurrent VTE) compared with those who pursued extended therapy.VTE patients with AnkS have clinical outcomes comparable to other inflammatory diseases but a significantly increased risk of recurrent VTE compared with non-inflammatory patients, suggesting that extended anticoagulation strategies may be warranted.

Chronic inflammation plays a key role in the development and progression of atherosclerotic cardiovascular disease (ASCVD) and its complications. Despite the use of blood pressure-, lipid-, and glucose-lowering therapies as well as antithrombotic agents, the lifetime residual cardiovascular (CV) risk in patients with ASCVD remains high. Because chronic inflammation remains an unaddressed risk factor, anti-inflammatory therapy has the potential to further lower residual CV risk in these patients. Low-dose colchicine (0.5 mg daily) has emerged as a promising low-cost oral anti-inflammatory therapy for this indication. In patients with chronic coronary syndrome (CCS), low-dose colchicine was well-tolerated and reduced the risk of myocardial infarction, stroke, coronary revascularization, and CV death. However, trials in patients with acute coronary syndrome (ACS) yielded conflicting results, and two trials in patients with ischemic stroke did not show a benefit. In patients with peripheral artery disease (PAD), preliminary observational data suggested a potential benefit, and a randomized trial is currently underway to examine its efficacy in reducing CV and limb events. The long-term safety data for low-dose colchicine in ASCVD are reassuring. Although pooled data from trials in ASCVD show a small (0.55%) absolute increase in the risk of hospitalization for gastrointestinal events, adverse signals were not observed for serious infection, cancer, or severe myotoxicity. In this article, we review the clinical studies of colchicine that examined its risk-benefit for the prevention of CV events in patients with ASCVD, discuss clinical and research implications, and highlight knowledge gaps.

The outcome of venous thromboembolism in patients with cancer is worse than in patients without cancer, with a higher risk of recurrences, bleeding and death. However, these risks appear to vary depending on the cancer type. While in some tumours the risk of recurrences outweighs the risk of bleeding, in others the risk of major bleeding (MB) during the anticoagulation markedly exceeds the risk of a recurrent event. Balancing these risks could be helpful to tailor the management of cancer-associated thrombosis (CAT) and improve outcomes. In this article, published data from recent randomized clinical trials as well as from some large registries that have reported separated outcomes of CAT depending on cancer type were reviewed. A careful balance of the risk of recurrences and MB events could provide useful insights for clinicians for individualizing treatment strategies in order to improve the outcomes of CAT, as well as for the design of future clinical trials.