Clinical and Applied Thrombosis/Hemostasis最新文献

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.

Carotid artery stenosis (CAS) often goes undetected until it reaches an advanced stage, which can result in serious complications. The present study evaluated the potential of long noncoding RNA (lncRNA) LINC01088 as a biomarker for CAS. 92 CAS patients and 92 healthy controls (Control group) were included. RT-qPCR was performed to assess the relative levels of LINC01088 and miR-195-5p. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic potential of LINC01088. The relationship between LINC01088 and miR-195-5p was identified by luciferase reporter assay. Proliferation, migration, and apoptosis in human aortic endothelial cells (HAECs) were assessed using CCK8, transwell, and flow cytometry assay. DAVID was employed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. CAS patients showed decreased LINC01088 expression and increased miR-195-5p expression compared to Control, with a negative correlation between their expression levels in CAS. LINC01088 demonstrated high sensitivity and specificity in distinguishing CAS patients from healthy individuals. LINC01088 directly targets miR-195-5p. Upregulation of LINC01088 reversed the effects of ox-LDL treatment, restoring proliferation and migration while reducing apoptosis in HAECs. However, miR-195-5p mimic reduced the protection of LINC01088 on HAECs proliferation, migration, and apoptosis. For miR-195-5p target genes, GO revealed protein metabolism pathways and KEGG highlighted the p53 and MAPK signaling pathways. The present study revealed the diagnosis value of LINC01088. LINC01088 reversed ox-LDL-induced proliferation, apoptosis, and migration by acting as sponges of miR-195-5p in HAECs. LINC01088 may serve as a protective biomarker in CAS progression.

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.

BackgroundHemophilia A and B are X-linked recessive bleeding disorders caused by deficiencies of coagulation factors VIII and IX, respectively. These conditions lead to spontaneous bleeding, joint damage, inhibitor development, and the burden of frequent intravenous infusions. Concizumab, a monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), is a novel non-factor therapy that enhances thrombin generation. This systematic review evaluates the efficacy and safety of concizumab prophylaxis in patients with hemophilia A and B.MethodsThis systematic review was conducted in accordance with PRISMA guidelines. Randomized controlled trials (RCTs) assessing the use of concizumab in hemophilia A or B were identified through a comprehensive search of electronic databases. Outcomes of interest included annualized bleeding rate (ABR), thrombin generation, bleeding episodes, immunogenicity, and adverse events. The Cochrane Risk of Bias Tool 2.0 was used for quality assessment.ResultsFive studies were included. Concizumab prophylaxis was associated with a notable reduction in ABR, with reported decreases from 9.4 to 1.3 episodes/year and from 19.6 to 2.9 episodes/year in hemophilia A, and from 14.9 to 1.6 episodes/year in hemophilia B. Thrombin generation increased in a dose-dependent manner and stabilized by week 24. Across all studies, bleeding episodes were significantly reduced. Adverse events were primarily mild to moderate. No thromboembolic events were reported.ConclusionConcizumab appears to be an effective and safe prophylactic treatment for patients with hemophilia A and B, demonstrating consistent reductions in bleeding rates and enhanced thrombin generation. Further long-term studies are warranted to establish its sustained safety and efficacy.

BackgroundAlthough hospital readmission after pulmonary embolism (PE) is common, there is limited evidence on the comparative risk of readmission between rivaroxaban and apixaban. This study compared the real-world risk of all-cause hospital readmission among patients with PE treated with rivaroxaban or apixaban.MethodsThis retrospective study used data from Mass General Brigham's Research Patient Data Registry (01/2013-05/2023) to identify adult patients newly initiated on rivaroxaban or apixaban during a PE-related hospitalization (discharge = index). Patients with venous thromboembolism in the 3 months prior to the index PE hospitalization were excluded. All-cause hospital readmissions at 30, 60, and 90 days post-index were assessed using Kaplan-Meier analysis and were compared between cohorts using hazard ratios (HRs), 95% confidence intervals (CIs), and p-values from Cox proportional hazards regression models. Inverse probability of treatment weighting was used to adjust for baseline confounding.ResultsIn total, 686 rivaroxaban (mean age: 59.5; female: 50.1; Quan-Charlson comorbidity index: 1.51) and 2207 apixaban (mean age: 60.6; female: 50.8; Quan-CCI: 1.58) initiators were included. Rivaroxaban was associated with a 26% lower risk of all-cause hospital readmission at 30 days post-index (12.3% vs 16.5%; HR [95% CI]: 0.74 [0.58, 0.94]; P = .012). Risk of hospital readmission was also significantly lower at 60 days (17.0% vs 22.3%; HR [95% CI]: 0.74 [0.61, 0.91]; P = .004) and 90 days post-index (21.6% vs 25.6%; HR [95% CI]: 0.81 [0.68, 0.98]; P = .029).ConclusionsRivaroxaban was associated with significantly lower risk of all-cause hospital readmission within 90 days post-discharge from PE-related hospitalization than apixaban.

BackgroundThis study aimed to investigate the association of pan-immune-inflammation value (PIV), PIV/HDL-C (high-density lipoprotein cholesterol), PIV*LDL-C (low-density lipoprotein cholesterol) with the prognosis of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).MethodsA total of 1360 patients with ACS undergoing PCI were consecutively enrolled in this study. They were divided into major adverse cardiovascular events (MACEs) (n = 58) and non-MACEs (n = 1302) groups. The PIV, PIV/HDL-C, and PIV*LDL-C values were measured. The endpoints were MACEs, including cardiogenic mortality, recurrence of myocardial infarction, in-stent restenosis, and rehospitalization for severe heart failure.ResultsThe multivariable Cox regression analysis showed that PIV ≥355.79 (hazard ratio [HR]: 2.006, 95% confidence interval [CI]: 1.165-3.455), PIV/HDL-C ≥ 282.86 (HR: 1.987, 95% CI: 1.119-3.527), and PIV*LDL-C ≥ 1431.58 (HR: 2.071, 95% CI: 1.206-3.556) were all independent predictors of MACEs in patients with ACS undergoing PCI (all P < .05). The cumulative survival rates were significantly lower for patients with higher PIV, PIV/HDL-C, and PIV*LDL-C than for patients with lower values of these indices (log-rank tests: all P < .05).ConclusionHigher PIV, PIV/HDL-C, and PIV*LDL-C were independent prognostic factors for patients with ACS undergoing PCI and may be novel biomarkers for predicting MACEs.

Recurrent spontaneous miscarriage (RSM) is a gynecological complication has multifactorial etiologies including genetic factors. However, role of thrombophilic gene polymorphisms in RSA among Jordanian women is limited. This study explores the association between polymorphisms in SERPINC1, PROC, PROS1, PROZ, F5, F13A1, and CPB2 and RSA risk in Jordanian pregnant women. Blood samples were taken from 188 women with recurrent spontaneous miscarriage (RSM) and 193 control subjects without a history of miscarriage. Genomic DNA was extracted and analyzed for polymorphisms of thrombophilic genes using Kompetitive Allele Specific Polymerase Chain Reaction. The SNPStats tool was used to assess haplotype, genotype, and allele frequencies, with chi-square (χ²) tests employed to evaluate statistical significance. A total of seven thrombophilic genes were analyzed. The rs8178607 polymorphism in PROS1 was significantly associated with RSA in Jordanian women under the allelic (OR = 2.06, p = .014), codominant (OR = 2.05, p = .021), dominant (OR = 1.27, p = .015), and overdominant (OR = 1.91, p = .03) genetic models. Additionally, significant associations in the recessive model were observed for the rs1799810 and the rs1926447 polymorphisms in PROC (OR = 1.66, p = .038) and in CPB2 (OR = 1.89, p = .046), respectively. Our data preliminary demonstrates that the rs8178607, rs1799810, and rs1926447 genotypes of PROS1, PROC, and CPB2 respectively, are associated with an increased risk of RSA among Jordanian pregnant women. Further investigations with larger cohorts and family-based analyses are essential to elucidate the genetic variation of biochemical pathways and mechanisms influences recurrent miscarriage susceptibility.

Objective: To study the link between free thyroxine (FT4) levels and mortality in hypertensive patients. Methods: Utilizing data from the National Health and Nutrition Examination Survey performed in the United States from 2007 to 2012. Results: This study included 3365 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Weighted Cox regression model, Kaplan-Meier (KM) survival analysis, and restricted cubic spline (RCS) were used to analyze the link between FT4 levels and mortality in hypertensive patients. Furthermore, subgroup analyses and interaction analyses were carried out to evaluate the stability of links between FT4 levels and all-cause mortality across different subgroups of hypertensive patients. In the weighted Cox regression model, after adjusting for all covariates, FT4 levels treated as a continuous variable were positively linked to all-cause mortality in hypertensive patients (HR = 1.08,95% CI: 1.04-1.12, P < .001). When FT4 levels were treated as a categorical variable according to quartiles, the fully adjusted model found that the highest quartile of FT4 posed a greater all-cause mortality risk in hypertensive patients relative to the lowest quartile (HR = 1.47, 95% CI:1.01-2.15, P = .045). Based on the Kaplan-Meier survival curve, all-cause mortality was notably higher in groups Q3 and Q4 relative to FT4 levels in groups Q1 and Q2 (P < .001). The RCS curve revealed that the all-cause mortality in hypertensive patients exhibited a nonlinear increasing trend with rising FT4 levels (P for nonlinear = .033). The results were further validated by subgroup and sensitivity analyses, which confirmed their robustness and reliability. Conclusion: The level of FT4 is strongly linked to the all-cause mortality risk in hypertensive patients.

IntroductionThrombophilia (TP) has been proposed as a potential contributor to preeclampsia (PE). However, there is not a clear consensus on testing PE patients for TP due to contradictory evidences on this association. This study aims to identify what conditions of women with PE are associated with acquired and hereditary TP, and, additionally, to build a model of TP probability using these characteristics.Material and MethodsRetrospective unicentric analysis of women diagnosed with PE referred for TP testing between May 2019 and May 2024.ResultsIn 95 women, 19 (20%) tested positive for TP, of which nine (47%) had antiphospholipid syndrome (APS), six (32%) were heterozygous for PT G20210A, two (11%) had ADAMTS13 deficiency, one (5%) had PS deficiency and one (5%) had heterozygous FV Leiden. In multivariate analysis, intrauterine growth retardation (IUGR; odds ratio (OR) 0.08, 95% confidence interval (CI) 0.01-0.55) and history of previous abortions (OR 0.22, 95%CI 0.06-0.96) were negatively associated with TP. The group of women with both, one or none of those traits showed respectively a TP prevalence of 0%, 15% and 32%. The higher the prevalence of TP, the lower the incidence of placental insufficiency and prematurity (P < .05).ConclusionsIn pregnant women with PE, a history of previous abortions and IUGR were independently associated with the absence of TP. Women without these characteristics would probably benefit most from a Hematology consultation that includes a TP screening. A multinational standard TP screening framework for future studies is warranted to further our understanding of the role of TP in PE and to identify risk-groups for testing.

BackgroundCritically ill patients in intensive care unit (ICU) are at high risk of venous thromboembolism (VTE). The standardized prophylaxis of VTE in these patients and the appropriate prevention protocols are not very clear.MethodWe enrolled 426 patients admitted to respiratory intensive care unit (RICU), all of them underwent Padua risk scoring and patients at high risk of VTE also underwent bleeding risk scoring. We compared the VTE prevention methods that followed the guidelines between two different bleeding risk groups and the VTE incidence of these two groups. We also analyzed the risk factors for VTE in RICU patients.ResultsIn patients admitted to RICU, the rate of overall VTE prophylaxis was 71.3% (295/414), but the rate of standardized prophylaxis of VTE was only 32.6% (135/414). The standardized prophylaxis rate of VTE in high-risk bleeding patients was 40.3%, much higher than the 22.2% in low-risk bleeding patients (P < 0.001). There was also a significant difference in the incidence of VTE between the two groups (26.9%vs3.4%, P < 0.001). 70 (16.9%) patients in RICU developed VTE, the multivariable logistic regression analysis showed that immobilization time, pulmonary encephalopathy, oral or inject corticosteroids, trauma or surgery within 3 months were independent risk factors of VTE in patients admitted to RICU, while pharmacological prophylaxis was a protective factor for VTE. The receiver operating characteristic (ROC) curve showed that the above composite indicators had a higher predictive value for RICU patients with VTE, with a ROC area under the curve (AUC) of 0.925 (95%CI 0.894-0.956, P < 0.001).ConclusionAlthough the overall prophylaxis rate of VTE in patients admitted to RICU was high, the rate of standardized prevention was not ideal. Pharmacological prophylaxis may play an important role in preventing VTE in RICU patients and fruther studies are needed to explore the optimal thromboprophylaxis protocol for critically ill patients.