OBJECTIVE: The association between thyroid function, coagulation and venous thromboembolism (VTE) has been reported in observational studies with conflicting findings. This study aimed to elucidate the causal effects of thyroid function on coagulation and VTE from a genetic perspective.
METHODS: Two sample Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies in a European population. Coagulation status was associated with nine coagulation-related factors (F VIII, F IX, F XI, Fibrinogen, Antithrombin-III, Thrombomodulin, Plasminogen activator inhibitor-1, Protein C and Protein S). Inverse variance weighting with random effect method was used as the main analytic approach with MR-Egger, weighted median, simple mode and weighted mode methods serving as complements. Sensitivity analyses including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis were conducted to further assess the reliability of results.
RESULTS: No genetic causal effects of thyroid function on VTE (including pulmonary embolism and deep venous thrombosis) were found. Genetically, hyperthyroidism was suggestively related to decreased Antithrombin-III (β: -0.04 [95% CI: -0.06 to - 0.01], p = 0.010) and Protein C (β: -0.03 [95% CI: -0.06 to 0.00], p = 0.045). No notable associations were observed between other thyroid function parameters and coagulation-related factors.
CONCLUSIONS: We provide suggestive genetic evidence supporting the causal effect of hyperthyroidism on decreased level of anticoagulant factors including Antithrombin-III and Protein C. However, whether this genetic causality could lead to clinically significant hypercoagulable state and increased risk of VTE in hyperthyroid population needs to be further addressed.

Stroke leaves a great economic burden due to its high morbidity and mortality. Rapid revascularization of targeted vessel(s) is the effective treatment for ischemic stroke, but subsequent ischemia-reperfusion (I/R) injury is a common complication following revascularization, leading to microcirculation dysfunction and infarct volume increase. Thrombo-inflammation, the interaction between thrombosis and inflammation, plays a critical role in the pathophysiology of ischemic stroke. In the context of I/R injury, thrombo-inflammation consists of platelet activation, endothelial injury, and inflammatory cell infiltration. Numerous studies are devoted to exploring methods of regulating thrombo-inflammation to mitigate I/R injury post-stroke, including blocking activations of platelets and neutrophils. Drugs such as antiplatelet medications, anticoagulants, and glucocorticoids have been confirmed to have the potential to regulate thrombo-inflammation. Furthermore, several recently developed drugs have also shown promises in relieving I/R injury by manipulating thrombo-inflammation. However, the majority of these studies are still in the preclinical stage. Herein, in this review, we will address the mechanisms of thrombo-inflammation in ischemic stroke, related research advances, and particularly the clinical feasibility of thrombo-inflammation as a therapeutic strategy against I/R injury.

OBJECTIVE: More evidence supports the benefits of batroxobin combined with anticoagulation in correcting acute cerebral venous thrombosis (CVT). The dynamic fluctuations of peripheral blood platelets, fibrinolysis, and coagulation biomarkers during this therapy were analyzed.
METHODS: We investigated batroxobin\'s effects on the antithrombotic system under two regimens. The pretreatment group included patients on anticoagulants for at least 1 week before starting batroxobin. The simultaneous treatment group began both treatments upon admission. The control group received only anticoagulation. Batroxobin was given on alternate days at doses of 10BU, 5BU, and 5BU, totaling three doses. Anticoagulation was continuous. Baseline data were T0; the next day after each batroxobin dose was T1, T2, and T3. Data from these four time points was analyzed.
RESULTS: The time-point paired sample T-test results of the pretreatment group [n = 60; mean age (SD), 43.3(16.5); 38 (63.35%) women] showed that batroxobin significantly inhibited ADP-induced platelet aggregation rate (T1-T0: p = 0.015; T2-T0: p = 0.025; T3-T0: p = 0.013), decreased fibrinogen level (T1-T0: p < 0.001; T2-T0: p < 0.001; T3-T0: p < 0.001), and increased D-dimer (T1-T0:p < 0.001; T2-T0: p < 0.001; T3-T0: p < 0.001), TT (T1-T0:p = 0.046; T2-T0: p = 0.003; T3-T0: p < 0.001), and APTT (T1-T0:p = 0.021; T2-T0: p = 0.012; T3-T0: p = 0.026). Compared to the control group, the simultaneous treatment group showed significantly higher TT (T2: p = 0.002; T3: p = 0.004) and D-dimer (T1: p < 0.001; T2: p < 0.001; T3: p < 0.001) values, while fibrinogen (T2: p < 0.001; T3: p < 0.001) levels were significantly lower. Using batroxobin can alleviate the amplitude of changes in coagulation indicators other than TT caused by anticoagulants. The above conclusions are consistent with the results of repeated measurement data analysis.
CONCLUSIONS: Batroxobin can significantly inhibit ADP-induced platelet aggregation rate, increase D-dimer, decrease fibrinogen, and prolong TT and APTT in the presence of anticoagulant agents. Using batroxobin can reduce the amplitude of changes in coagulation indicators caused by anticoagulants. These results reveal the potential mechanism of batroxobin combined with anticoagulation in the safe and effective treatment of CVT.

Warfarin, with its narrow therapeutic range, requires the understanding of various influencing factors for personalized medication. Vascular senescence, marked by vascular stiffening and endothelial dysfunction, has an unclear effect on the efficacy and safety of warfarin. Based on previous studies, we hypothesized that vascular senescence increases the risk of bleeding during warfarin therapy. This study aimed to explore these effects using animal models and clinical cohorts. We established rat models of vascular senescence and calcification using d-galactose (D-Gal), vitamin D and nicotine (VDN). After validating the models, we examined changes in the International Normalized Ratio (INR) at fixed warfarin doses (0.20 and 0.35 mg/kg). We found that vascular senescence caused significantly elevated INR values and increasd bleeding risk. In the prospective clinical cohort study(NCT06428110), hospitalized warfarin patients with standard dose adjustments were divided into vascular senescence and control groups based on ultrasound and Computed Tomography (CT) diagnosis. Using propensity score matching (PSM) to exclude the influence of confounding factors, we found that the vascular senescence group had lower steady-state warfarin doses and larger dose adjustments, with a higher probability of INR exceeding the therapeutic range. The vascular senescence group tended to experience more bleeding or thromboembolic/ischemic events during one year of follow-up, while there was no statistical difference. In conclusion, vascular senescence leads to unstable INR values and increases higher bleeding risk during warfarin therapy, highlighting the importance of considering vascular senescence in future precision warfarin therapies. Significance Statement Many factors influence warfarin efficacy, however, the effect of vascular senescence remains unclear. This study aimed to investigate the effects of vascular senescence on the efficacy and safety of warfarin. Through both rat models and clinical cohort studies, our findings indicated that vascular senescence may compromise the stability of warfarin, presenting challenges in maintaining its efficacy and safety.

The formation of flocs is crucial in the coagulation process of water treatment. However, the nature of ligand exchange on the surface of primary nanoparticles (PNPs) during floc formation requires further investigation to enhance our understanding of the coagulation mechanism. Phosphate (P) is a ubiquitous nutrient ion in aquatic surface water, in this study, the impact of P on floc growth under different pH conditions were investigated. The results revealed that floc growth patterns depended on both P dosage and pH. The mode of ligand exchange between P and in-situ formed ferric hydroxide within a pH range of 5 to 10 was further explored, and remarkable disparities in pH changes induced by P addition were observed. At lower pH levels, OH- release occurred relatively slowly, stabilizing with continued P addition. At neutral pH, OH- release was comparatively higher with P addition, while under alkaline conditions, both the quantity of OH- and its release rate decreased. It was deduced that Fe-OH21/2+ sites function as \"active sites,\" while Fe-OH1/2- sites act as \"inert sites\" on the surface of PNPs formed during flocculation. These sites are crucial in the interconnections between flocs formed during coagulation and in floc growth. Analyses of Fe PNPs by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM), with and without P addition, revealed that the introduction of P inhibits or interferes with the self-crystallization of Fe PNPs through chemical coordination reactions. The results offer deeper insights into the coagulation mechanism and the transformation of Fe flocs in raw waters containing P during water treatment practices.

The quartz sand-enhanced coagulation (QSEC) is an improved coagulation method for treating water, which uses quartz sand as a heavy medium to accelerate the sedimentation rate of flocs and reduce the sedimentation time. The factors that influence the QSEC effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc., and their reasonable setting is critical to the result of water treatment. This paper aimed to study the optimal conditions of QSEC; first, single-factor tests were conducted to explore the optimal range of influencing factors, followed by response surface methodology (RSM) tests to accurately determine the optimum values of significant factors. The results show that the addition of quartz sand did not improve the water quality of the coagulation treatment, it took only 140 s for the floc to sink to the bottom, and the sediment volume only accounted for 12.2% of the total sewage. The quartz sand dosage, the coagulant dosage, and sewage pH all had a significant impact on the coagulation effect, and resulted in inflection points. A QSEC-guiding model was derived through RSM tests, and subsequent model optimization and experimental validation revealed the optimal conditions for treating domestic sewage as follows: the polyaluminum chloride (PAC) dosage, cationic polyacrylamide (CPAM) dosage, the sewage pH, quartz sand dosage, stirring time, and settling time were 0.97 g/L, 2.25 mg/L, 7.22, 2 g/L, 5 min, and 30 min, respectively, and the turbidity of the treated sewage was reduced to 1.15 NTU.

UNASSIGNED: Postpartum hemorrhage (PPH) is the primary cause of maternal mortality globally, with uterine atony being the predominant contributing factor. However, accurate prediction of PPH in the general population remains challenging due to a lack of reliable biomarkers.
UNASSIGNED: Using retrospective cohort data, we quantified 48 cytokines in plasma samples from 40 women diagnosed with PPH caused by uterine atony. We also analyzed previously reported hemogram and coagulation parameters related to inflammatory response. The least absolute shrinkage and selection operator (LASSO) and logistic regression were applied to develop predictive models. Established models were further evaluated and temporally validated in a prospective cohort.
UNASSIGNED: Fourteen factors showed significant differences between the two groups, among which IL2Rα, IL9, MIP1β, TNFβ, CTACK, prenatal Hb, Lymph%, PLR, and LnSII were selected by LASSO to construct predictive model A. Further, by logistic regression, model B was constructed using prenatal Hb, PLR, IL2Rα, and IL9. The area under the curve (AUC) values of model A in the training set, internal validation set, and temporal validation set were 0.846 (0.757-0.934), 0.846 (0.749-0.930), and 0.875 (0.789-0.961), respectively. And the corresponding AUC values for model B were 0.805 (0.709-0.901), 0.805 (0.701-0.894), and 0.901 (0.824-0.979). Decision curve analysis results showed that both nomograms had a high net benefit for predicting atonic PPH.
UNASSIGNED: We identified novel biomarkers and developed predictive models for atonic PPH in women undergoing \"low-risk\" vaginal delivery, providing immunological insights for further exploration of the mechanism underlying atonic PPH.

Considering the challenges for both single and traditional two-stage treatments, advanced oxidation and biodegradation, in the treatment of actual coking wastewater, an intimately coupled catalytic ozonation and biodegradation (ICOB) reactor was developed. In this study, ICOB treatment significantly enhanced the removal of Cu2+, Fe3+, and color by 39 %, 45 %, and 52 %, respectively, outperforming biodegradation. Catalytic ozonation effectively breaking down unsaturated organic substances and high-molecular-weight dissolved organic matter into smaller, more biodegradable molecules. Compared with biodegradation, the ICOB system significantly increased the abundances of Pseudomonas, Sphingopyxis, and Brevundimonas by ∼ 96 %, ∼67 %, and ∼ 85 %, respectively. These microorganisms, possessing genes for degrading phenol, aromatic compounds, polycyclic aromatics, and sulfur metabolism, further enhanced the mineralization of intermediates. Consequently, the ICOB system outperformed biodegradation and catalytic ozonation treatments, exhibiting chemical oxygen demand removal rate of ∼ 58 % and toxicity reduction of ∼ 47 %. Overall, the ICOB treatment showcases promise for practical engineering applications in coking wastewater treatment.

Aim: To explore potential value of inter-alpha-trypsin inhibitor heavy chain-4 (ITIH4) for coronary artery disease (CAD) diagnosis. Patients & methods: We recruited the patients who received coronary arteriography (CAG) examination. The enzyme-linked immunosorbent assay was used to detect plasma ITIH4. Results: ITIH4 level was lower expression in CAD patients than that in patients of control group, and was negatively correlated with C-reactive protein (CRP). ITIH4 level is no differences between ST-elevated myocardial infarction (STEMI) and non-ST-elevated myocardial infarction (NSTEMI) patients. However, its expression was significantly correlated with D-Dimer and thrombin time, and the logistic analysis confirmed predictive value of ITIH4 for visible thrombus in coronary. Conclusion: ITIH4 may be a useful biomarker in CAD diagnosis, and to predict visible thrombus in coronary.
What is this summary about? ITIH4 is present in human plasma and related to several diseases. Coronary artery disease (CAD) is one of the most popular diseases in the world. We test the diagnosis value of ITIH4 in CAD patients.What were the results? ITIH4 level was lower in CAD patients than that in control patients. ITIH4 was correlated with C-reactive protein. ITIH4 may play a role in clotting system. ITIH4 was also correlated with D-Dimer and thrombin time. ITIH4 level in thrombus patients was lower than that in without thrombus patients. ITIH4 could be used to predict coronary visible thrombus.What do the results mean? ITIH4 may be a useful diagnosis biomarker in CAD patients.

UNASSIGNED: Five secreted platelet protein disulfide isomerases (PDIs) and 1 transmembrane PDI regulate platelet function and thrombosis. Thioredoxin-related transmembrane protein 1 (TMX1) was the first member of the PDI family found to negatively regulate platelet aggregation and platelet accumulation in vivo. The effect of TMX1 on coagulation is unknown.
UNASSIGNED: To determine the effect of TMX1 on coagulation.
UNASSIGNED: TMX1-/- mice were used to study platelet accumulation and fibrin deposition in vivo in the laser-induced thrombosis injury model. Annexin V deposition at the site of vascular injury was studied using conditional TMX1 knockout mice. Annexin V binding to platelets was studied using human platelets, anti-TMX1 antibodies, and TMX1-deficient platelets.
UNASSIGNED: TMX1-/- mice had increased fibrin deposition that was reversed with infusion of recombinant TMX1. Infusion of recombinant TMX1 inhibited platelet accumulation and fibrin deposition in wild-type mice and inhibited fibrin deposition in β3-null mice. Platelet accumulation is absent in β3-null mice, suggesting that TMX1 inhibits coagulation independently of platelets. Annexin V binding was increased in activated human platelets incubated with an anti-TMX1 antibody and mouse platelets lacking TMX1. Addition of recombinant TMX1 decreased annexin V binding to platelets. Annexin V binding was increased at the site of vascular injury in Tie2-Cre/TMX1fl/fl mice deficient in endothelial cell TMX1.
UNASSIGNED: TMX1 decreases coagulation at the site of vascular injury and negatively regulates phosphatidylserine exposure on endothelial cells and platelets.