Biomarkers Profile in Provoked Versus Unprovoked Deep Venous Thrombosis.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

The Relevance of Thrombo-Inflammatory Biomarkers and Their Relationship with Circulating Glycosaminoglycans in End-Stage Renal Disease Patients.

En-stage renal disease (ESRD) is a growing public health problem. The atherosclerotic cardiovascular complications are the leading causes of mortality and morbidity in the ESRD. In this study, we sought to quantify the levels of thrombo-inflammatory biomarkers in an ESRD patients in comparison to healthy controls to determine their relevance in thrombo-inflammation and adverse outcomes. The levels of D-Dimer, C-reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1) antigen, functional PAI-1, thrombin activatable fibrinolysis inhibitor, tissue plasminogen activator, von Willebrand factor, and anti-PF4 IgG and microparticle (MP) activity were quantified by using commercially available ELISA immunoassays for each of the ESRD (n = 73) and control plasma samples (n = 10). The levels of endogenous glycosaminoglycans (GAGs) were quantified by utilizing a Heparin Red Probe (Redprobes UG, Germany). The collected data were analyzed to demonstrate the relationship between various parameters. All the tested biomarkers were increased in ESRD patients in comparison to healthy controls (p < 0.05). These biomarkers have shown significant correlations within each other except for anti-PF4 Ig G and MPs. The CRP levels were significantly higher in patients who had coronary artery disease (CAD) (p < 0.05), but there was no significant difference in other biomarkers according to the cardiovascular outcomes. In the multivariate analysis, the CRP (odds ratio: 1.19; 95% confidence interval: 1.01-1.41; p: 0.03) value was an independent predictor of CAD. In this study, we demonstrated increased levels of 10 different biomarkers in ESRD patients. The CRP levels can be a good predictor of CAD in ESRD patients.

Potency Adjusted Blended Heparin of Bovine, Ovine, and Porcine Heparin Exhibit Comparable Biologic Effects to Referenced Single-Sourced Porcine Heparin.

Introduction: Bovine and ovine mucosa represent alternate anticoagulants to porcine mucosa for production of unfractionated heparin (UFH). Standardized heparins from various sources can be blended and potency adjusted, blended heparins exhibit comparable effects as single-sourced porcine UFH. This study evaluated the pharmacologic profile of blended heparin and compared their activities to that of single sourced porcine, ovine, and bovine heparins. Methods: The anticoagulant effects of gravimetric and potency-adjusted heparins were evaluated with aPTT, TT, anti-Xa, anti-IIa, ACT, and TGA studies. Protamine sulfate studies were used for neutralization potential of each of the individual heparins. Results: The potency-adjusted heparins demonstrated comparable aPTT, TT, anti-Xa, anti-IIa, and ACT values at all concentrations (U/mL). However, in gravimetric studies, bovine heparin consistently showed lower values with the exception of thrombin generation inhibition studies. The protamine sulfate neutralization studies demonstrated complete neutralization at all concentrations for the potency-adjusted heparins. However, at gravimetric concentrations, minor differences were noted in the neutralization profile in each of these heparins. Conclusion: These studies support the hypothesis that blended heparin from bovine, ovine, and porcine tissue, when standardized in unit-equivalent proportions, exhibits a comparable anticoagulant profile to the single species derived heparins.

Predictive Role of Blood Cellular Indices and Their Relationship with Endogenous Glycosaminoglycans as Determinants of Inflammatory Biomarkers in Pulmonary Embolism.

INTRODUCTION: In this study, we profiled the levels of blood cellular indices, endogenous glycosaminoglycans (GAGs) and inflammatory biomarkers in a cohort comprised of pulmonary embolism (PE) patients, to determine their inter-relationships. Identification of this relationship may provide insight to the complex pathophysiology of PE and the predictive role of blood cellular indices in acute PE patients. MATERIALS AND METHODS: Plasma samples from PE patients and healthy controls were analyzed for thrombo-inflammatory biomarkers (IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-É£, TNF-α, IL-1α, IL-1ß, MCP-1, EGF, D-dimer, CRP and MMP-9) using biochip array and ELISA methods. The endogenous GAG levels were quantified using a fluorescence quenching method. The data regarding the blood cellular indices were collected through the review of patient medical records and analyzed to demonstrate their relationship. RESULTS: The levels of inflammatory biomarkers and endogenous GAGs were elevated in acute PE patients compared to controls (P < .05). Most of the blood cellular indices have shown significant differences in acute PE patients compared to controls (P < .05). The levels of inflammatory biomarkers, endogenous GAGs and the blood cellular indices have shown significant associations in correlation and multivariable analysis. While NLR, PLR and SII were significantly predicting the 30-day mortality, PNR, ELR and EMR were not sufficient to predict 30-day mortality in acute PE. CONCLUSION: Our results show that the increased thrombo-inflammatory response is associated with the release of GAGs and the changes in blood cellular indices. The predictive role of the blood cellular indices for mortality is dependent on their relationship with the inflammatory response.