Clinical and Applied Thrombosis/Hemostasis最新文献

Thrombophilia in venous thromboembolism (VTE) is multifactorial. Von Willebrand factor (vWF) plays a major role in primary hemostasis. While elevated vWF levels are well documented in VTE, findings related to its cleaving protease (ADAMTS-13) are contradicting. The aim of this study was to determine vWF, ADAMTS-13, and the multifactorial Thrombospondin-1 (TSP-1) protein levels in patients after 3-6 months following an unprovoked VTE episode. We also explored a possible association with factor V Leiden (FVL) mutation. vWF, ADAMTS-13 and TSP-1 were analyzed using ELISA kits in 60 VTE patients and 60 controls. Patients had higher levels of vWF antigen (P = .021), vWF collagen-binding activity (P = .008), and TSP-1 protein (P < .001) compared to controls. ADAMTS-13 antigen was lower in patients (P = .046) compared to controls but ADAMTS-13 activity was comparable between the two groups (P = .172). TSP-1 showed positive correlation with vWF antigen (rho = 0.303, P = .021) and negative correlation with ADAMTS-13 activity (rho = -0.244, P = .033) and ADAMTS-13 activity/vWF antigen ratio (rho = -0.348, P = .007). A significant association was found between the presence of FVL mutation and VTE (odds ratio (OR): 9.672 (95% confidence interval (CI) 2.074-45.091- P = .004), but no association was found between the mutation and the studied proteins (P > .05). There appears to be an imbalance between vWF and ADAMTS-13 in VTE patients even after 3-6 months following the onset of VTE. We report that the odds of developing VTE in carriers of FVL mutation are 9.672 times those without the mutation, but the presence of this mutation is not associated with the studied proteins.

Inflammation is pivotal in the pathogenesis and development of cerebral venous thrombosis (CVT). Herein, we aimed to assess the anti-inflammatory effects of batroxobin combined with anticoagulation in CVT. Participants were categorized into the batroxobin group (batroxobin combined with anticoagulation) and the control group (anticoagulation only). Regression analysis was employed to explore the association between the number of episodes of batroxobin administration and the fluctuation of inflammatory indicators, as well as the proportion of patients with inflammatory indicators that were reduced after batroxobin use. Twenty-three cases (age: 39.9 ± 13.8 years, female: 39.1%) in the batroxobin group and 36 cases (40.3 ± 9.6 years, 52.8%) in the control group were analyzed. Compared to the control group, batroxobin combined with anticoagulation significantly decreased fibrinogen (P < .001), platelet-lymphocyte ratio (PLR) (P = .016) and systemic immune-inflammation index (SII) (P = .008), and increased the proportion of the patients with lower fibrinogen (P < .001), neutrophil-lymphocyte ratio (NLR) (P = .005), PLR (P = .026), and SII (P = .006). Linear analysis showed that as the number of episodes of batroxobin administration increased, the fibrinogen (P < .001), the PLR (P = .001), and the SII (P = .020) significantly decreased. Logistic regression analysis showed as the number of episodes of batroxobin administration increased, the ratio of the patients with decreased NLR (P = .008) and PLR (P = .015), as well as SII (P = .013), significantly increased. Batroxobin could decrease NLR, PLR, and SII in CVT. The effect was related to the number of episodes of batroxobin administration. Besides reducing fibrinogen and indirect thrombolysis effects, this may be another critical benefit of batroxobin for CVT.

Introduction and objectives: The present study aimed to investigate different peripheral lymphocyte subsets in patients with severe hemophilia A (HA) and factor VIII (FVIII) inhibitor production. For this, age-matched cases of 19 FVIII inhibitor-positive (IP), 21 FVIII inhibitor-negative (IN) and 45 healthy controls were selected for study.

Methods: Flow cytometry was used to analyze the peripheral lymphocyte subsets, including T, B, natural killer (NK) and NKT cells. The T cell subsets included CD3 + CD4-CD8- [double negative T (DNT)], CD3 + CD4 + CD8+ [double-positive T (DPT)], CD3 + CD4 + CD8- and CD3 + CD4-CD8+ T cells. Pairwise comparisons of absolute lymphocyte subset values were conducted among the three groups. The cut-off value for absolute lymphocyte counts was determined using receiver operating characteristic curve analysis.

Results: The results demonstrated that the absolute values of DPT cells in the IN and IP groups were significantly lower than those in the healthy control group (P = 0.007). The DNT values were also lower in severe HA patients with or without inhibitor than those in healthy subjects, but these differences were not statistically significant (P = 0.053). In addition, the absolute value of CD4+ Th cells in the IP group was lower than that in the healthy controls (P = 0.013). Although not statistically significant (P = 0.064), the absolute values of NKT cells were higher in the IN group compared with the IP group, and higher in the IP group compared with the healthy control group. There were no statistically significant differences in total T, B, CD8 ⁺and NK cells among the IN, IP and healthy control groups. The cut-off value for absolute CD4+ Th cells in the IN group was < 598/µl.

Conclusion: The decrease in absolute values of CD4+ Th cells in severe HA patients may contribute to the establishment of infused FVIII immune tolerance. If the CD4+ Th value remains > 598/µl, clinicians should be vigilant for possible FVIII inhibitor production, especially on days prior to FVIII exposure.

Non-ST-segment elevation acute myocardial infarction (NSTEMI) is a life-threatening clinical emergency with a poor prognosis. However, there are no individualized nomogram models to identify patients at high risk of NSTEMI who may undergo death. The aim of this study was to develop a nomogram for in-hospital mortality in patients with NSTEMI to facilitate rapid risk stratification of patients. A total of 774 non-diabetic patients with NSTEMI were included in this study. Least Absolute Shrinkage and Selection Operator regression was used to initially screen potential predictors. Univariate and multivariate logistic regression (backward stepwise selection) analyses were performed to identify the optimal predictors for the prediction model. The corresponding nomogram was constructed based on those predictors. The receiver operating characteristic curve, GiViTI calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. The nomogram model consisting of six predictors: age (OR = 1.10; 95% CI: 1.05-1.15), blood urea nitrogen (OR = 1.06; 95% CI: 1.00-1.12), albumin (OR = 0.93; 95% CI: 0.87-1.00), triglyceride (OR = 1.41; 95% CI: 1.09-2.00), D-dimer (OR = 1.39; 95% CI: 1.06-1.80), and aspirin (OR = 0.16; 95% CI: 0.06-0.42). The nomogram had good discrimination (area under the curve (AUC) = 0.89, 95% CI: 0.84-0.94), calibration, and clinical usefulness. In this study, we developed a nomogram model to predict in-hospital mortality in patients with NSTEMI based on common clinical indicators. The proposed nomogram has good performance, allowing rapid risk stratification of patients with NSTEMI.

The incidence of recurrent venous thromboembolism (VTE) changes over time from the first VTE event and depends on the presence of risk factors. In this study, we aimed to determine the yearly incidence of VTE recurrence during five years of follow-up after a first-ever VTE event. For this cohort study, we identified persons who experienced a validated first-ever VTE between 2006-2014 in northern Sweden. These patients' medical records were reviewed to identify recurrent VTE events during five years of follow-up. The yearly incidence rates (IRs) of recurrent VTE per 100 person-years were calculated and stratified into three groups defined by characteristics at the first-ever VTE event: no risk factors, cancer, or other risk factors. A total of 1413 persons experienced a first-ever VTE during the study period, of whom 213 experienced a recurrent VTE. Among persons without risk factors, the IR was 4.2 during the first year of follow-up, and 4.1 during the fifth year. Among persons with cancer, the IR was 9.5 during the first year, and 5.4 during the fifth year. Among persons with other risk factors, the corresponding IRs were 6.1 and 2.3. In conclusion, after a first-ever VTE event, persons with cancer had the highest recurrence rate during the first years of follow-up. Among persons with cancer who were alive after five years, the incidence of recurrent VTE during the fifth year was similar to that in participants without risk factors.

Angiopoeitin-2 (Ang2) is a vascular growth factor involved in regulating angiogenesis and endothelial remodeling. Higher Ang2 levels have been associated with mortality in the general population and among male hemodialysis patients, but its effects on concomitant heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) are unknown. Plasma samples from 73 ESRD patients and 40 healthy patients were analyzed for Ang2 concentrations using ELISA. Patient groups were stratified into those with or without HFrEF (EF < 50%). At two years following sample collection, the medical record was reviewed for mortality. The optimal cut-off value for Ang2 to predict all-cause mortality was 1671 pg/mL (AUC 0.73, sensitivity 0.714, specificity 0.750) based on the regression analysis. Statistical analyses included Mann-Whitney U tests, Cox proportional hazards model, and Log-rank test. Multiple comorbidities were present; coronary artery disease 46%, diabetes 69%, hypertension 97%, and smoking 49%. Patients with one- and two-year mortality had higher Ang2. Ang2 levels above the optimal cut-off are associated with mortality within the entire ESRD sample and within the group with both ESRD and HFrEF. In the Cox proportional hazards analysis, Ang2 levels were associated with mortality within the larger ESRD sample but not in the group with ESRD and HFrEF. Ang2 has potential as a non-specific biomarker for prognostication in patients with cardiorenal syndrome given its association with mortality, despite modest sex-based differences. Future research should be conducted with larger samples to evaluate if it has prognostic value in individuals with HFrEF and ESRD of varying severity and temporality.

Background: Emicizumab, a bispecific factor VIII mimetic antibody, was approved in 2018 for bleeding prophylaxis in congenital hemophilia A with or without inhibitors. Since then, several case reports and case series have described the off-label use of emicizumab in acquired hemophilia A (AHA), and data from two clinical trials were recently published (AGEHA, GTH-AHA-EMI).

Objectives: To describe the reported data on the outcomes of emicizumab, highlighting its benefit/risk profile in treatment.

Methods: We conducted a literature search in PubMed, Scopus, Cochrane, and Google Scholar up to August 2024, including all scientific articles reporting clinical outcomes of emicizumab use in patients with AHA.

Results: Thirty-two studies were included in the final review, covering a total of 171 AHA patients. The majority started emicizumab for active bleeding management and prophylaxis with various regimens. Follow-up duration and remission criteria varied. Two clinical trials supported the use of emicizumab for bleeding prophylaxis with a new dosing regimen and completion criteria. Bleeding was well managed in all cases, with no major recurrent bleeds. Some adverse events were reported : 3 cases of deep venous thrombosis, 2 cases of stroke, and 2 cases of anti-emicizumab drug antibodies developing in patients with thromboembolic risk factors.

Conclusions: Based on published data, emicizumab appears to be effective in bleeding management and prophylaxis in AHA patients, with a favorable benefit/risk profile.

Pulmonary embolism (PE) is an important cause of sudden death and is difficult to diagnose. Therefore unnecessary radiological investigations are often resorted to. Although some inflammatory parameters in the hemogram have been found to play a role in the diagnosis of PE, many parameters have not been adequately investigated. We aimed to evaluate potential inflammatory parameters in hemogram in the diagnosis of PE and to determine the parameters with the highest diagnostic value. This single-center, retrospective study was performed by evaluating 114 cases with suspected PE admitted to the emergency department between January 2017 and June 2022. Among 114 cases, 62 cases with a definitive diagnosis of PE by pulmonary computed tomography angiography served as the PE group and 52 cases without PE served as the control group. Admission hemogram parameters of both groups were recorded. Potential chronic diseases and acute conditions affecting hemogram were excluded from the study. In the multivariate model; immature granulocyte (IG), neutrophil/lymphocyte ratio (NLR), monocyte % and platelet large cell ratio (P-LCR) were found to be significantly and independently effective in differentiating cases with and without PE (P˂.05). Our findings suggest that high IG, high NLR, high monocyte %, and low P-LCR values have diagnostic value in cases with suspected PE. However the usability of IGs in the diagnosis of PE is a new finding. Hemogram is cheap, easily accessible, and potential inflammatory biomarkers in hemograms may increase physicians' awareness in the diagnosis of PE.

As a major global health concern, coronary artery disease (CAD) demands precise, noninvasive diagnostic methods like cardiopulmonary exercise testing (CPET) for effective assessment and management, balancing the need for accurate disease severity evaluation with improved treatment decision-making. Our objective was to develop and validate a nomogram based on CPET parameters for noninvasively predicting the severity of CAD, thereby assisting clinicians in more effectively assessing patient conditions. This study analyzed 525 patients divided into training (367) and validation (183) cohorts, identifying key CAD severity indicators using least absolute shrinkage and selection operator (LASSO) regression. A predictive nomogram was developed, evaluated by average consistency index (C-index), the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA), confirming its reliability and clinical applicability. In our study, out of 25 variables, 6 were identified as significant predictors for CAD severity. These included age (OR = 1.053, P < .001), high-density lipoprotein (HDL, OR = 0.440, P = .002), hypertension (OR = 2.050, P = .007), diabetes mellitus (OR = 3.435, P < .001), anaerobic threshold (AT, OR = 0.837, P < .001), and peak kilogram body weight oxygen uptake (VO₂/kg, OR = 0.872, P < .001). The nomogram, based on these predictors, demonstrated strong diagnostic accuracy for assessing CAD severity, with AUC values of 0.939 in the training cohort and 0.840 in the validation cohort, and also exhibited significant clinical utility. The nomogram, which is based on CPET parameters, was useful for predicting the severity of CAD and assisted in risk stratification by offering a personalized, noninvasive diagnostic approach for clinicians.

Background and aims: The diagnostic standard of coronary artery disease (CAD) is coronary angiography (CAG). Since CAG is an invasive procedure underscores the need for identifying non-invasive, effective, and innovative biomarkers. Our study aimed to retrospectively analyze hematological markers for predicting the severity of CAD.

Methods and results: Case data were collected from 195 CAD patients admitted to the hospital for CAG. According to Gensini score, patients were divided into mild, moderate, and severe CAD groups. Blood indexes and predictive efficacy of the triglyceride-glucose (TyG) index were retrospectively analyzed. Among 195 CAD patients, 81 had mild CAD, 60 had moderate CAD, and 54 had severe CAD. Sex, fast blood glucose (FBG), TyG index, and high-sensitivity C-reactive protein (hs-CRP) significantly differed among the three groups. The TyG index demonstrated higher values in patients with moderate (9.07[8.62-9.44]) and severe (8.98[8.46-9.45]) CAD compared to those with mild CAD (8.75[8.49-9.14]). The AUC of the TyG index was 0.615 (95% confidence interval (CI): 0.536-0.694, P =.004), with a cut-off value of 8.997, specificity of 0.704, and sensitivity of 0.535. Logistics analysis showed the risk of moderate and severe CAD with an odds ratio (OR) value of 2.595 (95% CI: 1.199-5.619, adjusted P = .016) following regrouping by the TyG index optimal cut-off value of 8.997. The TyG index combined with FBG and hs-CRP had an elevated AUC value, significantly higher than other combinations (P  =  .011 and 0.02, respectively).

Conclusions: The severity of CAD is positively correlated with an increased TyG index value. A combination of TyG, FBG, and hs-CRP has demonstrated improved diagnostic efficiency, suggesting its potential as a novel indicator for predicting and diagnosing CAD progression.