Clinical and Applied Thrombosis/Hemostasis最新文献

Introduction: Persistent elevation of biomarkers associated with endothelial dysfunction in convalescent COVID-19 patients has been linked to an increased risk of long-term cardiovascular complications, including long COVID syndrome. Sulodexide, known for its vascular endothelial affinity, has demonstrated pleiotropic protective properties. This study aims to evaluate the impact of sulodexide on serum levels of endothelial dysfunction biomarkers in patients during the convalescent phase of COVID-19.

Methods: We conducted a double-blind, single-center, randomized, placebo-controlled trial in Mexico, comparing sulodexide (250 LRU orally, twice daily) with placebo over 8 weeks in adult patients during early COVID-19 convalescence. Differences in serum biomarkers between the groups were analyzed using repeated measures and post hoc tests, with Thrombomodulin (TM) as the primary endpoint.

Results: Among 206 analyzed patients (103 in each group), at week 8, the sulodexide group exhibited significantly lower mean levels of Thrombomodulin (TM) (25.2 ± 7.9 ng/mL vs 29.9 ± 14.7 ng/mL, P = .03), von Willebrand Factor (vWF) (232 ± 131 U/dL vs 266 ± 122 U/dL, P = .02) and Interleukin-6 (IL-6) (12.5 ± 13.2 pg/mL vs 16.2 ± 16.5 pg/mL, P = .03) compared to the placebo group. D-dimer and C reactive protein (CRP) in the sulodexide group were also lowered. No significant differences were observed for P-selectin, fibrinogen, VCAM-1, or ICAM-1 levels.

Conclusions: Patients in the convalescent phase of COVID-19 who received sulodexide for eight weeks showed a reduction in TM, vWF, D-dimer, CRP, and IL-6 serum levels compared to placebo. These findings suggest a potential protective effect of sulodexide against thromboinflammation and endothelial damage.

Objective: Markedly elevated serum ferritin serves as a laboratory marker of macrophage activation syndrome and is associated with increased mortality in sepsis, where hyperinflammation, coagulopathy, and immune dysregulation interplay. Although laboratory studies suggest a relationship between hyperferritinemia and coagulopathy in sepsis, clinical evidence remains limited. This study aims to assess mortality risk and the interplay between hyperferritinemia (ferritin ≥ 500 ng/mL) and thrombocytopenia in two sequential cohorts of adult patients with sepsis.

Patients: Patients with sepsis (≥18 years old) admitted to adult ICUs at Beth Israel Deaconess Medical Center between 2001 and 2008, and 2008 to 2019, with at least one ferritin value recorded within a 48-h window preceding or following the initial ICU admission.

Results: Among 2339 eligible patients with hyperferritinemic sepsis, 921(39.4%) were categorized into the high ferritin (HF) group (ferritin ≥ 500 ng/mL). Multivariate logistic regression analysis revealed a significant association between the HF group and increased in-hospital mortality (p < .01). Survival analysis revealed significantly lower survival probabilities at 28 and 90 days in the HF group compared to the low ferritin group. The interaction between the HF group and thrombocytopenia revealed a statistically significant association with in-hospital mortality. Furthermore, causal mediation analysis showed that platelet count mediated 12.6% (95% CI: 0.063-0.27; p < .001) of the effect of elevated ferritin levels on in-hospital mortality.

Conclusions: Hyperferritinemia is associated with an increased mortality risk in adult septic patients. Thrombocytopenia not only interacts with hyperferritinemia but also serves as a mediating factor in its impact on mortality.

Introduction: Preoperative patients with knee osteoarthritis have a significantly increased risk of venous thromboembolism (VTE). While the Caprini risk assessment model offers some clinical guidance in predicting deep vein thrombosis (DVT), it has a relatively low predictive accuracy. Enhancing the model by integrating biomarkers, such as D-dimers, can potentially improve its accuracy. In this study, we explored the effectiveness of combining the Caprini risk model with D-dimer levels for individualized DVT risk assessment in patients with knee osteoarthritis.

Materials and methods: This retrospective cohort study included 1605 knee osteoarthritis patients scheduled for total knee arthroplasty from Peking Union Medical College Hospital, screened between January 2015 and December 2018. A revised Caprini risk stratification model was developed, and a predictive DVT model was developed based on this revised system. The sensitivity, specificity, and the area under the curve (AUC) were used to determine predictive effectiveness of the model.

Results: In the revised Caprini risk stratification, the incidence of DVT increased with higher risk levels: 2.52% in the low-risk group (scores 0-2), 2.88% in the moderate-risk group (score 3), 6.47% in the high-risk group (score 4), and 9.09% in the highest-risk group (score ≥ 5). The incidence of DVT was 3.869-fold higher in the highest-risk group and 2.676-fold higher in the high-risk group compared to the low-risk group (p = 0.013 and p = 0.014, respectively). Combining the revised Caprini risk stratification with D-dimer level demonstrated an improved AUC of 0.792, compared to D-dimer level alone (AUC 0.774) and the revised Caprini model alone (AUC 0.598). Furthermore, applying specific D-dimer thresholds across the four Caprini risk stratifications outperformed the combination of the revised Caprini model and D-dimer level in terms of AUC, specificity, and reduction in unnecessary ultrasonography. Using the Youden index, the AUC for the threshold-based method was slightly higher (0.775 vs 0.754, p = 0.310), with significantly better specificity (76.8% vs 63.6%, p < 0.001) and a greater reduction in ultrasound use (74.1% vs 61.4%). At a sensitivity of 85.5%, the differences were modest but still favored the threshold-based approach. At a sensitivity of 100%, the specificity (36.0% vs 24.7%, p < 0.001) and ultrasound reduction (34.8% vs 23.9%) were significantly better.

Conclusion: The revised Caprini risk stratification improves preoperative DVT prediction in patients with knee osteoarthritis. Incorporating specific D-dimer thresholds into the four-level Caprini risk model enhances specificity and reduces unnecessary ultrasonography, outperforming both the use of individual indicators and the combination of the revised Caprini model with D-dimer level.

Purpose: The purpose of this study was to investigate the clinical characteristics and risk factors for patients with lung cancer complicated by pulmonary embolism and to provide a reference for the early clinical identification of these patients.

Methods: Eighty patients with lung cancer complicated with pulmonary embolism who were treated at Bethune Hospital of Shanxi from October 2018 to October 2025 were compared with 80 patients with lung cancer without pulmonary embolism. The clinical data of the two groups of patients were collected and analysed.

Results: Compared with that in patients in the LC group, the proportion of patients with pulmonary interstitial fibrosis in the LP group was significantly greater (p < 0.05). The incidence of dyspnoea in the LP group was significantly greater than that in the LC group (p < 0.05). Compared with that in the LC group, the proportion of pulmonary artery compression in the LP group was significantly greater, and the difference was statistically significant (p < 0.05). In terms of pathological type, the proportion of adenocarcinoma patients in the LP group was significantly greater than that in the LC group (p < 0.05). In terms of tumor stage, the proportion of patients with stage III/IV disease in the LP group was significantly greater than that in the LC group, while the proportion of patients with stage I/II disease was significantly lower than that in the LC group, and the difference was statistically significant (p < 0.05). The neutrophil [NEUT (%)], prothrombin time (PT), white blood cell (WBC), carcinoma embryonic antigen (CEA) and D-dimer (DD) levels were significantly greater in the LP group than in the LC group (p < 0.05). In terms of treatment, the proportion of patients receiving systemic chemotherapy in the LP group was significantly greater than that in the LC group (p < 0.05). Logistic regression analysis revealed that adenocarcinoma, systemic chemotherapy and tumor stage III-IV were independent risk factors for lung cancer complicated with pulmonary embolism.

Conclusion: (1) Tumor stage (III/IV), systemic chemotherapy, and adenocarcinoma were independent risk factors for pulmonary thromboembolism in patients with lung cancer. (2) In addition, patients with LP were more likely to have pulmonary interstitial fibrosis, dyspnoea, compression of the pulmonary artery by the tumor location, biological targeted therapy, and abnormal increases in D-dimer, WBC, NEUT (%), CEA and PT levels as laboratory indicators. (3) Pulmonary thromboembolism should be considered in lung cancer patients with a combination of the factors described above.

Background: Carotid artery stenosis (CAS) may cause many cerebrovascular diseases, and a biomarker for screening and monitoring is needed. This study focused on the clinical significance of long-chain non-coding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) in patients with CAS and aimed to search for potential biomarkers of CAS.

Methods: Eighty-six asymptomatic patients with CAS and 60 healthy individuals were enrolled, with corresponding clinical data and serum samples collected. The expression of NORAD was detected by reverse transcription-quantitive PCR (RT-qPCR). All patients were followed up for 2 years to collected the occurrence data of cerebrovascular events, and Kaplan-Meier and Cox regression were used for data analysis. Receiver operator characteristic curve was used to analyze the diagnostic value of NORAD in distinguishing CAS patients from healthy people, and to evaluate the prediction accuracy of NORAD.

Results: NORAD is overexpressed in the serum of CAS patients, and associated with patients' hypertension, TC, LDL-C levels and stenosis degree. NORAD has high sensitivity (88.37%) and specificity (80.00%) in the identification of CAS patients (AUC = 0.917). NORAD was independently related to the occurrence of cerebrovascular events (HR = 2.435, P = .003). a logistic regression risk model for predicting cerebrovascular events was constructed with the parameters including NORAD, TC and LDL.

Conclusion: NORAD can be used as a diagnostic and prognostic biomarker for CAS, and NORAD, total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) can be independently correlated to predict cerebrovascular events.

Limited available evidence comparing DOACs with warfarin suggests efficacy and safety of DOACs for CVT. We aimed to evaluate whether a specific DOAC is preferred for the treatment of CVT. This retrospective cohort study included adult patients with CVTs between September 2018 and September 2022 treated with a DOAC. The primary outcome was rate of partial or complete recanalization. Secondary outcomes included rate of recurrent VTE, CVT extension, major or clinically relevant non-major bleeding, and death within 180 days after DOAC initiation. Of 31 patients with CVT, 21 received apixaban, 7 received rivaroxaban, and 3 received dabigatran. Among those with repeat imaging, the primary composite outcome occurred in 100%, 80%, and 100% for each group, respectively (P = 0.34). One patient had extension of CVT while on apixaban and one patient had increased midline shift while on rivaroxaban. No other secondary outcomes were observed. There do not appear to be significant efficacy or safety differences between DOACs when used for CVT treatment, though larger studies are needed to validate these findings.

Convalescent plasma (CP) therapy for COVID-19 infection may have favorable safety but varying efficacy, with concerns about its procoagulant impact. We investigated whether administration of CP to hospitalized patients affects their coagulation profile. Fifty-four patients randomized in a double-blinded fashion received either placebo, low-titer CP (LCP) or high-titer CP (HCP). Donor blood samples were obtained at the time of the plasmapheresis, while recipient blood samples were collected before infusion, one day post-infusion and between two and six days after infusion. Routine laboratory follow-up, coagulation biomarkers, antiphospholipid antibodies, and thrombin generation (TG) were assessed. CP donors had normal blood cell counts and coagulation profiles, without differences between LCP and HCP donors at the baseline. All CP recipients were on low-molecular-weight heparin thromboprophylaxis at the time of the infusion. Despite randomization, the HCP group had lower baseline (p = 0.004) and Day 1 platelet counts (p = 0.019) than the LCP group. Von Willebrand antigen (VWF:Ag) levels clearly exceeded normal without differences at baseline. At Day 1, LCP recipients had higher VWF:Ag (mean ± SD 224 ± 15%) than HCP recipients (210 ± 8%) (p = 0.012). In all groups, overall 80% lupus anticoagulant was positive. Baseline TG variables were comparable, but again LCP recipients exhibited higher endogenous thrombin potential (ETP) (1313 ± 535 nM.min) (p = 0.038) and peak TG (184 ± 106 nM) (p = 0.037) than the HCP group (870 ± 425 nM.min and 86 ± 54 nM). Our findings show that LCP increases VWF:Ag levels and enhances TG despite the thromboprophylaxis. These results suggest that HCP induces less hypercoagulability than LCP, which may contribute to the variability in CP efficacy.

Rivaroxaban was FDA-approved in 2019 for venous thromboembolism (VTE) prophylaxis in acutely ill hospitalized patients. Little to no published data is available to determine the level of correlation between rivaroxaban drug concentration and UFH/LMWH calibrated anti-Xa assays at VTE prophylactic doses of rivaroxaban 10 mg daily. This study aimed to assess the anticoagulant effects of rivaroxaban prophylactic doses using LMWH calibrated anti-Xa levels at the University of Colorado Hospital (UCH). This prospective cohort study evaluated seventy-three hospitalized patients at UCH taking rivaroxaban 10 mg daily for VTE prophylaxis from June 2023 to April 2024. Patients were enrolled if they were between the ages of 18-89 years old, received rivaroxaban 10 mg daily, and had active orders for coagulation studies. A linear regression model and coefficient of determination was used to evaluate the primary outcome assessing the relationship between rivaroxaban drug concentrations and anti-Xa levels. The LMWH calibrated anti-Xa assays were strongly correlated to rivaroxaban concentrations ranging from (1-59 ng/ml) in patients receiving rivaroxaban 10 mg daily, r² = 0.99 (P < .00001). Our data suggests that LMWH calibrated anti-Xa levels less than 1.40 IU/ml may indicate minimal anticoagulation effects for rivaroxaban 10 mg daily. The secondary outcomes assessing the relationship between rivaroxaban drug concentrations and time since administration, r² = 0.16 (P = .049), as well as time since administration of rivaroxaban and anti-Xa activity, r² = 0.15 (P = .066), were weakly correlated and showed a trend. Characterizing the high correlation between anti-Xa levels and rivaroxaban plasma concentrations at 10 mg daily doses, provides additional insight to rivaroxaban's anticoagulant effects in clinical practice. This can be beneficial in various clinical scenarios and has the potential to reduce the waiting time for clinical procedures.

Objectives: To explore the risk factors for thrombi occurring in patients with immune thrombocytopenia (ITP) and establish a risk prediction model to better predict the risk of thrombosis in patients with ITP.

Methods: We retrospectively analyzed 350 ITP patients who had been hospitalized in the First People's Hospital of Yunnan Province between January 2024 and June 2024. For all patients, we recorded demographic characteristics and clinical data, analyzed the risk factors for thrombosis in ITP patients and then developed a risk prediction model.

Results: Stepwise logistic regression analysis indicated that a high D-dimer level, a low PC (platelet count) and a high Padua score were independent risk factors for thrombosis in ITP patients. According to multivariate analysis, a predictive model for thrombus risk showed that the area; the area under the ROC curve (AUC) was 0.673 (95% CI: 0.615-0.730) and the maximum Youden index, sensitivity and specificity were 0.272, 47.0% and 80.2%, respectively.

Conclusion: A high D-dimer level, low PC, and high Padua score were shown to be independent risk factors for thrombosis in ITP patients. Also, the study showed that these three risk factors might be used as a risk predictors for thrombosis in ITP patients to some extent.

Aim: To evaluate the longitudinal coagulation profile after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematological malignancies.

Methods: Several coagulation variables were measured at predetermined time points for two years after HSCT in 30 pediatric patients.

Results: At six months post-HSCT, endothelial activation was reflected by 1.4-fold increase in circulating von Willebrand factor activity (p < 0.05), and by 2-fold increase in thrombin-antithrombin complex levels (p < 0.05), suggesting sustained coagulation system activity. In six patients with chronic graft-versus-host disease (cGVHD), specifically in those having gastrointestinal (GI) tract cGVHD, we observed continued longitudinal alterations in the coagulation system. The activities of both, coagulation factors (FV, FVII, FVIII, fibrinogen), and natural anticoagulants (antithrombin and protein C) were higher than prior to conditioning (p < 0.05) at most time points in patients with cGVHD. Moreover, fibrin turnover marker D-dimer was elevated from 6 to 18 months after HSCT (p < 0.05).

Conclusion: Pediatric patients undergoing HSCT demonstrate prolonged derangement of the coagulation system, with a new alleviating balance after 6 months post-HSCT. However, in patients with cGVHD, and in particular when cGVHD affects the GI tract, the persisting derangement of coagulation suggest its contributing role in cGVHD and related complications.