Thrombosis Journal最新文献

Background: To investigate the association between inflammatory indices-systemic immune-inflammation index (SII), monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and preoperative deep vein thrombosis (DVT) in patients undergoing total joint arthroplasty (TJA).

Methods: We created the receiver operator characteristic (ROC) curve using the ratios of SII, MLR, NLR, PLR to DVT before TJA, divided the enrolled patients into groups based on the cut-off value, and then analyzed risk factors for DVT before TJA in the multivariate binary logistic regression analysis.

Results: A total of 2125 patients were enrolled and preoperative DVT occurred in 110 cases (5.18%). Based on the ROC curve, we determined that the cut-off values for SII, MLR, NLR, and PLR were 470*10⁹ /L, 0.306, 2.08, and 127; and the areas under the curve (AUC) were 0.623, 0.601, 0.611, and 0.62. Multivariate binary regression analysis revealed that the risk of preoperative DVT in TJA patients with SII ≥ 470*10⁹/L, MLR ≥ 0.306, PLR ≥ 127, and NLR ≥ 2.08 increased by 2.26 (P < 0.001, 95% confidence interval (CI) [1.52-3.37]), 1.92 (P = 0.002, 95% CI [1.28-2.9]), 2.1 (P < 0.001, 95% CI [1.4-3.16]), and 1.94 (P = 0.002, 95% CI [1.29-2.92]) times, respectively. Age, P < 0.001, odds ratio (OR) = 1.08, 95%CI [1.05-1.10]; corticosteroid use, P = 0.002, OR 3.8, 95% CI [1.94-9.22]).

Conclusion: We found that higher SII, MLR, NLR, and PLR levels, age, and corticosteroid use were independent risk factors for preoperative DVT in patients undergoing TJA.

Clinical trial registration: ChiCTR2100054844; Registration Date: 2021.12.28.

Background: α-Klotho may involve in the occurrence and development of venous thromboembolism (VTE). However, the underlying relationship between circulating α-Klotho levels and VTE is still unclear.

Methods: This two-sample Mendelian Randomization (MR) study aims to explore the causal associations of circulating α-Klotho levels with different types of venous thromboembolism. Data of exposure and outcomes were extracted from the genome-wide association study (GWAS) of the MRC Integrative Epidemiology Unit (MRC-IEU). The fixed inverse variance weighted (IVW), MR-Egger, MR-Robust Adjusted Profile Score (RAPS) and the weighted-median methods were utilized to investigate the causal associations of circulating α-Klotho levels with different types of VTE. The effect size was expressed as odds ratios (ORs) and 95% confidence intervals (CIs), and the False Discovery Rate (FDR) test was used for correction. The MR scatter plot and leave-one-out test were used for sensitivity analysis. In addition, reverse causal associations were assessed.

Results: IVW estimates suggested that an elevated circulating α-Klotho level was associated with lower odds of deep vein thrombosis (DVT) of lower extremities (OR = 0.992, 95%CI: 0.986-0.998, P = 0.0074), pulmonary embolism (PE) (OR = 0.474, 95%CI: 0.255-0.881, P = 0.0183), and DVT of lower extremities combined with PE (OR = 0.984, 95%CI: 0.971-0.997, P = 0.0175). However, after the FDR correction, only negatively causal association between circulating α-Klotho level and increased odds of lower-extremity DVT was statistically significant (FDR P = 0.0296). Also, there were no reverse causal associations between the circulating α-Klotho levels and different types of VTE (all P > 0.05). Additionally, both the MR scatter plots and leave-one-out test results showed that these causal associations were relatively robust.

Conclusion: An elevated circulating α-Klotho levels was associated with lower risk of DVT of lower extremities, PE, and DVT of lower extremities combined with PE, indicating α-Klotho has the potential to act as a target for early screening or treatment for VTE. However, the specific mechanism that α-Klotho influencing the occurrence of VTE still needed further exploration.

The REAADS VWF activity assay is often assumed to be specific for the A1 domain, the portion of VWF that binds platelet GPIbα. We tested this assay on the A1A2A3 region of VWF with each domain expressed independently of one another and together in combination as a tri-domain. The monoclonal antibody used in this assay is found to be insensitive to the single A domains and does not recognize free A1 domains as it is often assumed. Rather, we find the assay to effectively recognize A1A2A3 with the domains together in their natural glycosylated sequence context. Furthermore, type 2M and 2B Von Willebrand Disease mutations differentially disrupt the sensitivity of the assay, indicating that mutational effects on the structure of A1 in the A1A2A3 context concomitantly disrupt the epitope of the antibody. The REAADS VWF activity assay therefore is conformationally sensitive to the native quaternary association of the A domains together and it is not specific to freely exposed A1 domains.

Background: Acute pulmonary embolism (PE) is a serious and potentially fatal condition that is relatively rare in the pediatric population. In patients presenting with massive/submassive PE, catheter-directed Therapy (CDT) presents an emerging therapeutic modality by which PE can be managed.

Methods: Electronic databases were systematically searched through May 2024. This systematic review was performed in line with recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines and was registered in PROSPERO (Reg. no. CRD42024534229).

Results: Sixteen case reports/series were included in the quantitative analysis with a total population of 40 children diagnosed with PE. Of them, 21 were females and 19 were males. Massive PE was diagnosed in 15 patients and submassive PE was diagnosed in 17 patients. Complete resolution of PE happened at a rate of 68% (95%CI = 46-80%). Mortality was encountered at a rate of 18% (95%CI = 0.7-36%). PE recurred after CDT at a rate of 15% (95%CI = 2-28%). Non-major bleeding complicated CDT at a rate of 46% (95%CI = 25-66%, p = 0.163).

Conclusion: CDT can be utilized in the management of PE in children as a potential therapeutic option for selected patients. While the results of CDT interventions for pediatric PE are promising, further research -including well-conducted cohort studies- is required to validate those results.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), continues to pose significant clinical challenges despite advancements in medical care. Artificial intelligence (AI) presents promising opportunities to enhance the diagnosis, prediction, and management of VTE. This review examines the transformative potential of AI in thrombosis care, highlighting both the potential benefits and the challenges that need to be addressed. Through an analysis of current applications and future directions, the review underscores AI's role in advancing VTE management and improving clinical outcomes.

Background and aim: Bile acid metabolism plays a crucial role in maintaining the delicate balance between coagulation and anticoagulation processes. However, there is a paucity of research exploring the relationship between serum total bile acids (TBA) levels and the risk of deep venous thrombosis (DVT) in Chinese individuals. The primary objective of this study is to investigate the association between TBA levels and DVT occurrence in this population.

Methods and results: A cross-sectional study was conducted involving 4522 patients with suspected DVT, recruited from June 2018 to October 2023, at the First Affiliated Hospital of Xi'an Jiaotong University. After rigorous screening, 3165 patients were included in the final analysis. Participants were categorized into three TBA level groups: low-level (TBA < 2.3 umol/L), moderate-level (2.3 ≤ TBA < 4.3 umol/L), and high-level (TBA ≥ 4.3 umol/L). Logistic regression analysis was utilized to assess the relationship between TBA levels and DVT risk, adjusting for potential confounders. The median age of the study population was 63 years, with a median TBA level of 3.2 (1.9-5.3) umol/L. The findings revealed that, compared to the low-level TBA group, the moderate and high-level TBA groups had significantly higher odds ratios (ORs) for DVT, with ORs of 1.47 (95% CI: 1.21 to 1.78, P < 0.001) and 1.91 (95% CI: 1.58 to 2.32, P < 0.001), respectively. Interestingly, higher TBA levels were also associated with reduced odds of bleeding risk, with ORs of 0.81 (95% CI: 0.63 to 1.03, P < 0.001) and 0.64 (95% CI: 0.5 to 0.81, P < 0.001), respectively.

Conclusions: Our study provides evidence that serum TBA levels may serve as a risk factor for DVT in Chinese individuals, with higher levels conferring an increased risk. Additionally, unexpectedly, higher TBA levels were found to be associated with a reduced risk of bleeding complications. These findings have significant implications for understanding the complex interplay between bile acid metabolism and deep venous thrombosis, and warrant further investigation.

Background: Disseminated intravascular coagulation (DIC) is a severe complication in septic patients. The Japanese Ministry of Health and Welfare (JMHW)-DIC criteria, the first DIC criteria, were established in 1983, and several other criteria have been proposed since then, including the International Society on Thrombosis and Haemostasis (ISTH)-overt DIC criteria and the Japanese Association for Acute Medicine (JAAM) DIC criteria. This study aimed to look into the transition of DIC criteria used in randomized controlled trials (RCTs) for sepsis-induced DIC.

Methods: We searched PubMed, Scopus, and the Cochrane Central Register of Controlled Trials for English-language studies published through September 30, 2023. Two reviewers looked through citations that assessed the DIC criteria used in RCTs and their secondary analyses. Data on DIC diagnostic criteria, patient characteristics, interventions, and results were gathered.

Results: Twenty-one studies (thirteen RCTs: JMHW-DIC in 5, JAAM-DIC in 4, the sepsis-induced coagulopathy (SIC) in 2; and eight secondary analyses: ISTH-overt DIC in 3, single parameter in 5) were eligible for inclusion. Most RCTs were conducted in Japan, using the criteria of JMHW-DIC, which were followed by JAAM-DIC. Recently, SIC has been used in international RCTs. Meanwhile, other countries tended to conduct RCTs that focused on sepsis, with secondary analyses for DIC using the ISTH-overt DIC criteria.

Conclusions: The criteria used in RCTs have changed over decades, from the JMHW-DIC to the JAAM-DIC criteria, and the ISTH-overt DIC criteria were retained in the secondary analysis. Based on these findings, additional research is needed to determine the best criterion for diagnosing septic patients.

Background: Previous studies using genetically modified mouse models and inhibitors have shown that protein disulfide isomerase (PDI) family plays a significant role in arterial thrombosis. However, their role in venous thrombosis remains unknown. In this study, using gene-modified mouse models, we determined whether PDI family members contribute to venous thrombosis.

Methods: Mice deficient of the PDI family members, including PDI, PDIp, ERp57, PDIr, ERp5, ERp27, ERp29, TMX4, ERdj5, and ERp18, were generated. The venous thrombosis phenotype of these deficient strains was evaluated using an inferior vena cava (IVC) stenosis model. Moreover, the recombinant human ERp18 (rhERp18) protein was generated and its reductase activity was assessed using a Di-E-GSSG method. The effect of ERp18 in venous thrombosis was tested in the IVC stenosis model. The levels of von Willebrand factor (vWF) at the site of venous thrombi were measured.

Results: The mice deficient in PDI, PDIp, ERp57, PDIr, ERp5, ERp27, ERp29, TMX4, and ERdj5 had no effects on venous thrombosis in the IVC stenosis model. However, the mice lacking ERp18 developed significantly less venous thrombosis compared with the WT mice. ERp18 contains one CGAC active motif. When WT or ERp18-KO mice received injection of rhERp18-WT or inactive rhERp18-mutant (Mut) protein whose CGAC was mutated to SGAS, rhERp18-Mut protein inhibited venous thrombosis in the IVC stenosis model, suggesting that the role of ERp18 is dependent on its enzymatic activity. As determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining, the levels of vWF in the plasma at the site of venous thrombus in ERp18-KO mice were significantly lower than those in WT mice.

Conclusion: ERp18 enhances the development of venous thrombosis, and its function and its enzymatic activity and regulation of the vWF release are involved.

Objectives: Ischaemic stroke (IS) has become a major health problem globally as it is one of the leading causes of long-term disability and death. This study aimed to evaluate the association between red cell distribution width (RDW) to lymphocyte (LYM) ratio (RLR) and 30-day mortality risk in patients with IS.

Methods: The present study employed a retrospectively cohort study design with the adult data extracted from the Medical Information Mart for Intensive Care (MIMIC-III, MIMIC-IV) databases between 2001 and 2019. The RLR was measured using RDW and LYM. Confounders were adjusted in Cox proportional hazards model. The outcome was 30-day mortality. Univariable and multivariable Cox proportional hazards models were establised. A further analysis was conducted on the basis of subgroup stratification by heart failure (HF) (yes or no), atrial fibrillation or flutter (yes or no), hypertension (yes or no), dyslipidemia (yes or no), sepsis (yes or no), and age (≥ 65 years and < 65 years).

Results: In this study, 1,127 adult patients with IS were finally identified. Among them,818 patients survived (the survival group) and 309 patients died (the death group). The mean age was older in individuals from the death group than those from the survival group (70.19 years vs. 64.56 years). The elevated levels of RLR were linked to an increased risk of mortality within 30 days in patients with IS, with an HR of 1.70 (95% CI: 1.34-2.17). Subgroup analyses showed that high RLR levels was a significant risk factor for mortality at 30 days particularly in IS patients aged ≥ 65 years, HF, no atrial fibrillation or flutter, no hypertension, no dyslipidemia, and no sepsis.

Conclusion: Our study shows that high levels of RLR were associated with an increased risk of 30-day mortality in patients with IS, providing additional prognostic information for the treatment and supportive care of these patients.

Background: Lupus anticoagulant (LA) is an in vitro phenomenon with prolongation of a phospholipid-dependent coagulation test which is not due to an inhibitor specific to a coagulation factor. Occasionally, addition of normal pooled plasma to patient plasma with lupus anticoagulant potentiates the inhibitory effect of lupus anticoagulant in the mixture, resulting in a paradoxical prolongation instead of shortening of clotting time. The phenomenon has been termed the "lupus cofactor effect". Lupus anticoagulant are known to be associated with lymphoma and immunoglobulin M (IgM) paraproteinaemia. Cases of lymphoplasmacytic lymphoma with concomitant IgM paraproteinaemia and lupus anticoagulant demonstrating lupus cofactor phenomenon on activated partial thromboplastin time (APTT) assay has been reported previously. However, to our best knowledge, there were no reported cases of low grade B-cell lymphoma with positive LA results and lupus cofactor effect demonstrated on dilute Russell's viper venom time (DRVVT) and/or silica clotting time (SCT) assays in the literature.

Case presentation: We report two cases of low grade B-cell lymphoma associated with monoclonal IgM paraprotein, high levels of anti-cardiolipin IgM antibody and presence of lupus anticoagulant with lupus cofactor phenomenon on DRVVT and/or SCT assay.

Conclusions: Our cases demonstrate a possible novel association between low grade B-cell lymphoma, IgM paraproteinaemia, high levels of anti-cardiolipin IgM antibody and the presence of lupus cofactor effect on DRVVT and SCT assays. The DRVVT assay in the first patient and SCT assay in second patient were falsely negative in the neat sample or less diluted sample, and the lupus anticoagulant activities were only revealed on dilution of samples with normal pooled plasma. This highlights the potential importance of dilution of samples with normal pooled plasma while evaluating the LA status of low grade B-cell lymphoma patients with a markedly prolonged APTT and/or prolonged PT by DRVVT and SCT assays, especially if there is concomitant IgM paraproteinaemia and a high level of anti-cardiolipin IgM antibody.