Journal of Thrombosis and Thrombolysis最新文献

Pancreatic cancer (PC) has the highest risk of venous thromboembolisms amongst all cancer types. If not degraded through a process known as fibrinolysis, thrombi will continue to restrict blood flow and the transport of nutrients to downstream organs, which can lead to heart attack or stroke. While PC patients are known to be hypercoagulable and thus have an elevated thrombosis risk, the mechanism behind this behavior is not fully understood. We aimed to characterize alterations in clotting and fibrinolytic profiles in PC patients compared to healthy controls. Human blood plasma was collected from PC patients and healthy donor controls following institutional review board approval. We used kinetic turbidity to define the rates/timing of blood clot formation/degradation. Confocal and scanning electron microscopy were used to probe the effect PC has on fibrin network structure. Concentrations of proteins for clotting/fibrinolytic pathways were measured using ELISAs. PC patients were hypercoagulable compared to healthy donors with heightened fibrinogen concentration. A subset of patients were hypofibrinolytic, while most had similar fibrinolytic profiles to healthy. A comprehensive analysis revealed that delayed lysis in this subset was only present in patients with diabetes and/or COVID-19 due delayed clotting and, notably, elevated plasminogen activator inhibitor (PAI-1). In the general PC population, an extended PTT correlated with thicker fiber diameters while faster clotting resulted in smaller network pore size but was not correlated with lysis rate. Healthy, pooled plasma spiked with relevant concentrations of PAI-1 showed no difference in clot structure and comparable delays in lysis to patients. PAI-1, rather than network structure or other clotting/fibrinolytic factors, played a more significant role in hypofibrinolysis. PAI-1 inhibitors could be a prospective target for development of improved therapeutics to prevent restricted fibrinolysis.

Oral factor Xa inhibitors are preferred treatments for venous thromboembolism (VTE). While apixaban and rivaroxaban require an initial lead-in period, clinicians may reduce the period if patients have received prior therapeutic parenteral anticoagulation, although supporting evidence is limited. The purpose of this study is to evaluate bleeding and thrombotic events associated with reducing factor Xa inhibitor lead-in duration in patients who have received prior parenteral anticoagulation. This multicenter retrospective cohort study was conducted across 29 hospitals and included adult patients hospitalized with a new diagnosis of VTE who received at least 24 h of therapeutic parenteral anticoagulation before starting apixaban or rivaroxaban. Patients with active bleeding on admission, anticoagulation prior to admission, antiphospholipid syndrome, severe liver disease, or contraindicated medications were excluded. The primary outcome was time to VTE recurrence within six months. Cox proportional hazard model was used to control for potential confounding factors and a sensitivity analysis was performed using propensity matching. Among 1,424 patients included, 1,068 received a full lead-in and 356 a reduced lead-in regimen. No significant difference in time to recurrent VTE (HR 0.53; 95% CI, 0.20-1.37;p = 0.19) or major bleeding (HR 0.69; 95% CI, 0.31-1.56;p = 0.45) was observed after controlling for confounding factors. No difference in recurrent VTE and major bleeding persisted after propensity matching. Among patients transitioning from parenteral anticoagulation to oral factor Xa inhibitors, a reduced lead-in duration was not associated with increased VTE recurrence or major bleeding.

Immune checkpoint inhibitors (ICIs) are pivotal in cancer therapy, particularly but not solely for metastatic and advanced lung cancer. These monoclonal antibodies, targeting programmed cell death (PD)-1, ligand PD-L1, and cytotoxic T-lymphocyte antigen (CTLA)-4, enhance immune responses against tumors but can also trigger immune-related adverse events, including cardiotoxicity and vascular toxicity. Cardiotoxic effects, such as myocarditis, pericarditis, atrial arrhythmias, thrombosis, and vasculitis are significant concerns, particularly myocarditis that can be fatal. ICIs like pembrolizumab, nivolumab, and atezolizumab are widely used, with combination immunotherapy showing improved survival but higher myocarditis risk. Effective management of ICI-induced cardiovascular toxicity involves regular monitoring for physical findings, cardiac, inflammatory, and autoimmune biomarkers, electrocardiograms, CT angiograms, echocardiograms, and cardiac MRI as needed. Emergent treatment for ICI myocarditis and vasculitis includes immediate discontinuation of ICIs, high-dose corticosteroids, and supportive care. In severe or steroid-refractory cases, additional immunosuppressive therapies should be considered.

Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are at increased risk of atherosclerosis, including peripheral arterial disease (PAD). Critical limb ischemia (CLI) may complicate PAD and is associated with significant mortality and morbidity. Despite the increased risk of thrombosis with MPN, outcomes of CLI in MPN patients are unclear. We conducted an analysis utilizing the 2017-2020 National Readmission Database (NRD) of patients hospitalized for CLI with and without MPN. Patients with MPN were propensity score matched (PSM) with patients without MPN. Primary outcome was composite outcome of major adverse cardiovascular and limb events (MACLE). Logistic regression was utilized to estimate risk of MACLE in patients with MPN vs. without MPN. Inverse-probability treatment weighted (IPTW) analysis was performed to evaluate the effect of revascularization on MACLE in patients with MPN. A total of 102,598 patients were included, 931 (0.9%) had MPN. After PSM, MPN was associated with increased risk of MACLE (47.3% vs. 39.1%; OR 1.40, 95% CI 1.21-1.62). After IPTW, revascularization was associated with decreased risk of MACLE among patients with MPN (45.0% vs. 50.7%; OR 0.80, 95% CI 0.66-0.96). Among patients admitted with CLI, MPN was associated with increased risk of MACLE especially ET and MF phenotypes. Revascularization was associated with decreased risk of MACLE among patients with MPN. Further investigation is needed in order to improve outcomes in patients with MPN and CLI.

To examine whether the variability in ICD codes used for venous thromboembolism (VTE) definition among published studies affects VTE rates and associations detected from claims data. We extracted the ICD codes used for VTE definition from three published studies and proposed a new VTE definition based on clinical review of all utilized ICD codes. We compared these four definitions to assess differences in VTE rates and associated variables using a standardized scenario. We used a random 25% sample of the IQVIA PharMetrics® Plus for Academics database and analyzed patients undergoing gastrointestinal cancer surgery. The primary outcome was 90-day post-discharge VTE. The association of preoperative and intraoperative variables with VTE was assessed using bivariate and multivariable main effects logistic regression models. There were substantial differences in the use of ICD codes among the 4 VTE definitions (range 116 to 304 ICD-9/10 codes). Our population included 2,122 eligible patients (median age 59 years, 47% female) and the rate of VTE ranged from 2.3% to 4.4% using the four definitions. Multivariable analysis showed that the associations between VTE and age and type of surgery (esophageal surgery, gastric surgery) varied depending on the VTE definition used while the Elixhauser comorbidity score and liver surgery type were consistently associated with VTE. In this pilot study, differences in the incidence of VTE and associated risk factors were influenced by the choice of ICD9/10 codes used to define VTE. A standardized definition of VTE may improve the reproducibility and rigor of findings based on administrative claims data.

Atrial fibrillation is the most common cardiac arrhythmia and is a major risk factor for ischemic stroke. Atrial fibrillation and ischemic stroke are major cardiovascular complications in cancer patients, who have a higher burden and worse outcomes than the general population. Clinical risk stratification scores for stroke and bleeding, commonly used in the general population to estimate thromboembolic and bleeding risk, respectively, are less well validated in cancer patients, who have historically been excluded in clinical trials. There is a lack of consensus opinion on how to effectively risk-stratify cancer patients based on the currently available tools and a need for cancer-specific scores that offer a tailored approach to each patient in order to more effectively stratify ischemic stroke and bleeding risk in this cohort of patients. Cancer-mediated physiologic changes and adverse effects of antineoplastic therapy have been implicated as etiologies of the increased risk for both atrial fibrillation and ischemic stroke. Risk stratifying scores such as CHA₂DS₂-VASc and HAS-BLED, commonly used in the general population, are less well validated in cancer patients. There is a need for cancer-specific scores that can more effectively stratify ischemic stroke and bleeding risk in cancer patients, although given the heterogeneity of cancers, whether a "one score fits all" is uncertain.

Cancer and its treatment predispose to thromboembolic complications and thrombocytopenia. Thrombocytopenia does not protect against thromboembolism, but increases the risk of bleeding. The prognosis in venous thromboembolism (VTE) strictly depends on the efficacy of anticoagulation. The choice of anticoagulation strategy will depend on the severity of thrombocytopenia and its expected duration. Thrombotic risk is also important, determining the risk of death related to pulmonary embolism and the risk of recurrence/progression of VTE. Possible strategies include full anticoagulation and possible platelet transfusions, modification of the anticoagulation dose or interruption of anticoagulation. The review focuses on the possibilities of VTE treatment in the aspect of clinically significant thrombocytopenia with a platelet count below 50 × 10⁹/L (50 000/µl).

Several risk assessment models (RAMs) guide standardized prophylaxis to prevent venous thromboembolism (VTE) in trauma patients. The Caprini, Trauma Embolic Scoring System (TESS), and Greenfield Risk Assessment Profile (RAP) have been validated individually, but their predictive powers have not been directly compared in the general trauma population. This study evaluated the discriminatory ability of these three RAMs in trauma patients at an ACS-verified Level I Trauma Center. A retrospective review was performed of adult trauma patients in a single institution over one year. Demographic and clinical data were used to calculate Caprini, TESS, and RAP scores. The primary outcome was inpatient VTE. Logistic regression models - both combined and separate - generated receiver operating characteristic (ROC) curves for each score. Caprini served as the reference for comparing discriminatory ability. Among 1,276 patients, 33 (2.6%) developed inpatient VTE. Caprini, TESS, and RAP scores predicted VTE with odds ratios of 1.07 (95% CI 1.04-1.10), 1.39 (95% CI 1.23-1.56), and 1.20 (95% CI 1.12-1.29), respectively. ROC c-statistics were similar: Caprini 0.75 (95% CI 0.68-0.82), TESS 0.73 (95% CI 0.64-0.83), and RAP 0.70 (95% CI 0.60-0.79). Caprini, TESS, and RAP RAMs showed comparable moderate discriminatory ability (c-statistic > 0.70) in predicting inpatient VTE among trauma patients. No model was superior, suggesting any of these RAMs may guide standardized VTE prophylaxis in this population.

This study aimed to assess the prognostic value of the THRIVE scale in patients aged ≥ 60 years with acute ischemic stroke (AIS) after intravenous thrombolysis with the non-immunogenic staphylokinase compared with alteplase. The post-hoc analysis of FRIDA trial results was performed and enrolled patients aged ≥ 60 years were divided into two groups in accordance with the modified Rankin scale (mRS) score on day 90: good-outcome (mRS 0-2) and poor-outcome (mRS 3-6) groups. The receiver operating characteristic (ROC) curves were compared using Delong test. For all-cause mortality on day 90 the predicted AUC value by the THRIVE scale was 0.8 (0.71-0.9) in the non-immunogenic staphylokinase group and 0.76 (0.66-0.87) in the alteplase group (p = 0.57). For poor outcome, AUC value was 0.73 (0.64-0.82) in the non-immunogenic staphylokinase group and 0.79 (0.71-0.87) in alteplase group (p = 0.36). Thus, our study confirmed the prognostic value of the THRIVE scale to predict the outcomes of the patients aged ≥ 60 years treated with the non-immunogenic staphylokinase.

No sex-based data are available on the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 mg twice daily as alternative to its standard dose during the early phase after acute coronary syndrome (ACS). This post-hoc study is a sex-based secondary analysis of the PLINY THE ELDER randomized, crossover trial (NCT04739384), which compared ticagrelor 60 vs. 90 mg in elderly patients with ACS undergoing percutaneous coronary intervention (PCI). The primary endpoint was the pre-dose P2Y₁₂ reaction units (PRU) using the VerifyNow-P2Y₁₂ (Accumetrics, San Diego, CA, USA) at 14 days after treatment with ticagrelor 60 or 90 mg twice daily. A total of 50 elderly patients with ACS was included in the study. Of these patients, 28 (56%) were males and 22 (44%) females. The two doses of ticagrelor had a comparable PRU in both males (pre-dose: LSM difference_{60 vs. 90} -7.00, 95%CI -25.3 to 11.3, p = 0.44; post-dose: LSM difference_{60 vs. 90} 3.90, 95%CI -10.6 to 18.5, p = 0.59) and females (pre-dose: LSM difference_{60 vs. 90} -0.89, 95%CI -20.3 to 18.5, p = 0.93; post-dose: LSM difference_{60 vs. 90} -1.10, 95%CI -16.6 to 14.3, p = 0.88), with no evidence of sex-based interaction (pre-dose: p for interaction = 0.88; post-dose: p for interaction = 0.65). Consistently, transmittance aggregometry and multiple electrode aggregometry showed a similar pharmacodynamic profile between the two doses of ticagrelor in both male and female patients. Plasma levels of ticagrelor were significantly lower using the reduced dose of ticagrelor as compared with the standard dose in both males (pre-dose: LSM difference_{60 vs. 90} -212, 95%CI -391 to -33.0, p < 0.002; post-dose: LSM difference_{60 vs. 90} -308, 95%CI -510 to -105, p = 0.004) and females (pre-dose: LSM difference_{60 vs. 90} -131, 95%CI -332 to 69.1, p = 0.19; post-dose: LSM difference_{60 vs. 90} -670, 95%CI -898 to -442, p < 0.001). Ticagrelor 60 mg and ticagrelor 90 twice daily yielded the same magnitude of platelet inhibition among elderly patients with ACS irrespective of sex.