Prothrombin Activation Research Articles

What influences interruption of continuous renal replacement therapy in intensive care unit patients: A review with meta-analysis on outcome variables.

Evidence suggests that 8%-10% of ICU patients receive renal replacement therapy. However, there is a high rate of unplanned CRRT interruption, ranging between 17% and 74%. Studies on unplanned interruption of CRRT mainly focused on the retrospective investigation of related risk factors and conclusions have been diverse. This article aims to clarify the main influencing factors related to unplanned interruption of continuous renal replacement therapy (CRRT) in adult patients in intensive care units (ICUs). A literature review and meta-analysis were undertaken. Following the application of the Newcastle-Ottawa Scale (NOS), a total of 15 articles were included in a total of 2132 patients who underwent 3690 CRRT procedures and 2181 unplanned interruption times. The methodological guideline of a scoping review was applied for the evidence synthesis while applying the meta-analysis quantitative methodological guideline to identify and clarify main influencing factors related to unplanned interruption of CRRT. The reporting Prisma Protocol was followed. Longer filter life and prothrombin activation time, higher red blood cell count, greater transmembrane pressure, faster blood flow rate, intermittent saline irrigation, lower creatinine level, low prothrombin activity and pre-dilution are factors identified to potentially affect unplanned CRRT in ICU patients. Available evidence suggests four clinical challenges associated with unplanned CRRT interruption, namely: (a) effects of red blood cell count, filter life, cross-mode pressure, blood flow velocity, prothrombin activity and activated partial thrombin time on unplanned interruption; (b) influence of dilution mode on unplanned interruption; (c) influence of intermittent saline irrigation on unplanned interruption; (d) influence of Scr level on unplanned interruption. The potential to increase the ability to better manage unplanned CRRT in ICUs has been identified in this article and constitutes a relevant potential health care management contribution that can be implemented by nurses.

From Venom to Vein: Factor VII Activation as a Major Pathophysiological Target for Procoagulant Australian Elapid Snake Venoms.

Australian elapid snake venoms are uniquely procoagulant, utilizing blood clotting enzyme Factor Xa (FXa) as a toxin, which evolved as a basal trait in this clade. The subsequent recruitment of Factor Va (FVa) as a toxin occurred in the last common ancestor of taipans (Oxyuranus species) and brown snakes (Pseudonaja species). Factor II (prothrombin) activation has been stated as the primary mechanism for the lethal coagulopathy, but this hypothesis has never been tested. The additional activation of Factor VII (FVII) by Oxyuranus/Pseudonaja venoms has historically been considered as a minor, unimportant novelty. This study aimed to investigate the significance of toxic FVII activation relative to prothrombin activation by testing a wide taxonomical range of Australian elapid species with procoagulant venoms. The activation of FVII or prothrombin, with and without the Factor Va as a cofactor, was assessed, along with the structural changes involved in these processes. All procoagulant species could activate FVII, establishing this as a basal trait. In contrast, only some lineages could activate prothrombin, indicating that this is a derived trait. For species able to activate both zymogens, Factor VII was consistently more strongly activated than prothrombin. FVa was revealed as an essential cofactor for FVII activation, a mechanism previously undocumented. Species lacking FVa in their venom utilized endogenous plasma FVa to exert this activity. The ability of the human FXa:FVa complex to activate FVII was also revealed as a new feedback loop in the endogenous clotting cascade. Toxin sequence analyses identified structural changes essential for the derived trait of prothrombin activation. This study presents a paradigm shift in understanding how elapid venoms activate coagulation factors, highlighting the critical role of FVII activation in the pathophysiological effects upon the coagulation cascade produced by Australian elapid snake venoms. It also documented the novel use of Factor Va as a cofactor for FVII activation for both venom and endogenous forms of FXa. These findings are crucial for developing better antivenoms and treatments for snakebite victims and have broader implications for drug design and the treatment of coagulation disorders. The research also advances the evolutionary biology knowledge of snake venoms.

A-150 Extended Pre-Analytical Stability Validation for Coagulation Tests in Brazilian Clinical Laboratory

Abstract Background The transport of samples for coagulation tests is a challenge for clinical laboratories, due to their limited stability and short time for processing according to the manufacturer's recommendations. The objective of this study was to evaluate the possibility of extending the stability of samples collected for Prothrombin Time and Activity (PTA), activated Partial Thromboplastin Time (aPTT) and Fibrinogen tests for up to 10 hours at room temperature, in comparison with the stability described in the literature and by the manufacturer of the reagents (4 hours for aPTT, 8 hours for PTA and Fibrinogen). We verified the acceptability of the samples with a longer period between collection and analysis, including its impact on the clinical management Methods Four tubes of 3.2% sodium citrate from 40 volunteers were analyzed at times of up to 4 h, 6 h, 8 h and 10 h. The results obtained were compared with the dosage performed within 4 hours (recommended by manufacturer) and the Total Error obtained in the analysis of the samples was evaluated. The tubes remained at controlled room temperature of 15 to 25°C and were centrifuged at 1500 g for 15 minutes. Then, the analyses were performed by coagulometric method. Results The results showed safety in the analysis of samples for coagulation tests even within 10 hours after collection at ambient temperature and were within the Maximum Allowable Total Error (Carmen Ricós): 95% of the PTA results (TE 5,3%); 92.2% of aPTT results (TE 4,5%) and 98% of Fibrinogen analyses (TE 13,6%) (Figures 1, 2 and 3). In addition, even the results that exceeded the specified Total Error showed no impact on the clinical decision. Conclusions The study demonstrated that there was no significant loss of stability for the analyses of PTA, aPTT and Fibrinogen performed on samples kept at room temperature within 10 hours after collection. Most of the results showed variation within the specified Total Error and all results showed acceptability from a medical point of view

The Contrasting Effects of Bothrops lanceolatus and Bothrops atrox Venom on Procoagulant Activity and Thrombus Stability under Blood Flow Conditions.

Consumption coagulopathy and hemorrhagic syndrome are the typical features of Bothrops sp. snake envenoming. In contrast, B. lanceolatus envenoming can induce thrombotic complications. Our aim was to test whether crude B. lanceolatus and B. atrox venoms would display procoagulant activity and induce thrombus formation under flow conditions. Fibrin formation in human plasma was observed for B. lanceolatus venom at 250-1000 ng/mL concentrations, which also induced clot formation in purified human fibrinogen, indicating thrombin-like activity. The degradation of fibrinogen confirmed the fibrinogenolytic activity of B. lanceolatus venom. B. lanceolatus venom displayed consistent thrombin-like and kallikrein-like activity increases in plasma conditions. The well-known procoagulant B. atrox venom activated plasmatic coagulation factors in vitro and induced firm thrombus formation under high shear rate conditions. In contrast, B. lanceolatus venom induced the formation of fragile thrombi that could not resist shear stress. Our results suggest that crude B. lanceolatus venom displays amidolytic activity and can activate the coagulation cascade, leading to prothrombin activation. B. lanceolatus venom induces the formation of an unstable thrombus under flow conditions, which can be prevented by the specific monovalent antivenom Bothrofav®.

Full connected layer model with self-attention to hourly predict heparin dosage for perioperative cardiac surgery patients

BackgroundAnticoagulant therapy for patients who underwent cardiac surgery is a challenge. Both inadequate and excessive anticoagulation can cause fatal complications. Previous studies failed to provide real-time guidance for heparin pump speed adjustment. This study intended to provide a quantitative prediction model to optimize heparin dosage for cardiac surgery patients based on machine learning method. MethodsPatients who underwent cardiac surgery and admitted to intensive care unit in Peking Union Medical College Hospital (PUMCH) from January 2013 to December 2023 were retrospectively analyzed. In order to reach target activated partial thromboplastin time (aPTT), linear regression, SVM, XGBoost, LSTM, GRU, FC (Full Connected Layer) and FC + self-attention models were used to make hourly adjustment recommendation for administrations of heparin pump speed. Mean absolute square, and absolute percentage errors were used to evaluate the reliability of the models. SHAP method and feature cumulative effect were used to interpret the features of the FC + self-attention model. Safety and economic evaluation based on clinical compliance of this real-world data-oriented model was further analyzed. ResultsA total of 1080 patients including 112,554 heparin pump administrations were included in this study. Among seven candidate models, FC + self-attention model yielded the lowest mean absolute error of 0.9388 and 1.1325 in test and validation cohort. Gap to target aPTT, thrombin time, history of coronary heart disease, previous duration of arterial fibrillation and prothrombin activity were identified as important features affecting heparin adjustment. High compliance to FC + self-attention model may increase percentage of normal therapeutic time and decrease supratherapeutic therapeutic time and reducing blood draw until two consecutive normal therapeutic stabilization of aPTT. ConclusionsThis FC + self-attention model is potentially applicable for giving recommendation for healthcare providers to optimize heparin dosage for cardiac surgery patients.

Importance of the Cysteine-Rich Domain of Snake Venom Prothrombin Activators: Insights Gained from Synthetic Neutralizing Antibodies.

Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans that are bitten. While animal-derived polyclonal antivenoms are the primary treatment for snakebites, they often have limitations in efficacy and can cause severe adverse side effects. Building on recent efforts to develop improved antivenoms, notably through monoclonal antibodies, requires a comprehensive understanding of venom toxins. Among these toxins, snake venom metalloproteinases (SVMPs) play a pivotal role, particularly in viper envenomation, causing tissue damage, hemorrhage and coagulation disruption. One of the current challenges in the development of neutralizing monoclonal antibodies against SVMPs is the large size of the protein and the lack of existing knowledge of neutralizing epitopes. Here, we screened a synthetic human antibody library to isolate monoclonal antibodies against an SVMP from saw-scaled viper (genus Echis) venom. Upon characterization, several antibodies were identified that effectively blocked SVMP-mediated prothrombin activation. Cryo-electron microscopy revealed the structural basis of antibody-mediated neutralization, pinpointing the non-catalytic cysteine-rich domain of SVMPs as a crucial target. These findings emphasize the importance of understanding the molecular mechanisms of SVMPs to counter their toxic effects, thus advancing the development of more effective antivenoms.

Using heart rate variability to evaluate the association between the autonomic nervous system and coagulation function in patients with endometrial cancer.

The incidence of endometrial cancer (EC) is increasing worldwide, but the specific mechanism of coagulation dysfunction in EC is not fully understood. The objective of the present study was to explore the relationship between autonomic nervous system function and coagulation function in patients with EC using heart rate variability (HRV) analysis. The study included 100 patients with EC who were treated at the Department of Gynecological Oncology of The First Affiliated Hospital of Bengbu Medical University (Bengbu, China) from December 2021 to March 2023. A 5-min resting electrocardiogram was collected from each patient to analyze HRV parameters, including the time domain parameters standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD), and the frequency domain parameters low-frequency power and high-frequency power (HF). Blood samples were submitted to biochemistry tests to measure coagulation markers, namely prothrombin time (PT), international normalized ratio of PT (PT-INR), prothrombin activity (PTA), activated partial thromboplastin time (APTT) and fibrinogen. Bivariate Spearman correlation analyses revealed that PT, PT-INR and APTT were significantly positively correlated with SDNN, RMSSD and HF, while PTA was significantly negatively correlated with RMSSD. Following adjustments for confounding factors, namely age, body mass index, menopause, ligation of the fallopian tubes, diabetes, hypertension, adjuvant chemotherapy and mean heart rate, linear regression analysis demonstrated that SDNN, RMSSD and HF were independent factors influencing PT and PT-INR in patients with EC. The findings of the present study indicate that certain HRV parameters correlate with coagulation markers in EC and provide new insight into the occurrence of cancer-associated coagulation dysfunction.

Comparative efficacy of double plasma molecular adsorption system combined with plasma exchange versus plasma exchange in treating acute-on-chronic liver failure due to hepatitis B: A meta-analysis.

This meta-analysis aims to evaluate the effectiveness of the double plasma molecular adsorption system (DPMAS) in combination with plasma exchange (PE) compared to plasma exchange alone in the treatment of Acute-on-Chronic liver failure (LF) caused by hepatitis B. Until August 31, 2023, a comprehensive search of databases including Embase, Chinese Medical Journal Full-text Database, China Biomedical Literature Database, Wan Fang Medical Network, PubMed, and the Cochrane Library was carried out using keywords like "liver failure," "acute-on-chronic liver failure," "PE," "DPMAS," and related terms. The quality of the included studies was evaluated using QUADS (quality assessment of diagnostic accuracy studies). Software Revman 5.3 was used to examine the data, while Stata 15.1 was used to run Egger's test. Following thorough screening, 452 patients who received PE alone and 429 patients who received DPMAS in addition to PE were included. Every study that was included was of a high caliber. When comparing the DPMAS plus PE group to the PE alone group, the total bilirubin reduction was considerably higher (mean difference [MD] = -49.09, 95% confidence interval [CI]: -54.84 to -43.35, p < .00001). Prothrombin activity (PTA; MD = -1.53, 95% CI: -3.29 to -0.22, p = .09), albumin (ALB; MD = -0.58, 95% CI: -1.57 to 0.41, p = .25), prothrombin time (PT; MD = -0.07, 95% CI: -1.47 to 1.34, p = .92), and platelet count (PLT; MD = -0.08, 95% CI: -1.33 to 1.66, p = .90) did not differ significantly. The improvement in international standardized ratio (INR) was significantly greater in the PE group (MD = 0.07, 95% CI (0.03, 0.10), p = .0001). When combined with DPMAS, PE has been shown to be more effective in lowering total bilirubin levels. PE can also lower INR in individuals who have hepatitis B-related ACLF. This therapeutic strategy also lessens the need for plasma transfusions.

Laboratory profiling of patients with long COVID in the Brazilian Amazon region: A cross-sectional study.

The condition commonly referred to as long coronavirus disease (COVID) is characterized by the continuation of symptoms, sometimes accompanied by new symptoms that persist after the resolution of acute coronavirus disease 2019 (COVID-19). This observational cross-sectional study investigated 332 patients with long COVID in the Brazilian Amazon region. The study aimed to elucidate the systemic interactions associated with long COVID by compiling the findings related to hematological, coagulation, immunological, metabolic, hepatic, renal, and muscular profiles. Participants with long COVID were identified using rigorous criteria and underwent thorough laboratory examinations. The obtained data were subsequently analyzed, allowing for comparisons, associations, and correlations between findings within distinct groups in the study. Significant associations were observed between hospitalization during the acute phase and persistent laboratory abnormalities, suggesting a potential link between acute severity and long-term effects. Notably, individuals with long COVID for over a year exhibited elevated levels of monocytes, prolonged prothrombin times, reduced prothrombin activity, high levels of lactate dehydrogenase, and an increased frequency of qualitative C-reactive protein detection. This study provides valuable insights into the laboratory risk profile of patients with long COVID, particularly in the unique context of the Amazon region, where patients exhibit persistent symptoms lasting up to 1261 days.

Antithrombotic Effect of Oil from the Pulp of Bocaiúva-Acrocomia aculeata (Jacq.) Lodd. ex Mart. (Arecaceae).

The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). In vitro toxicity was evaluated with the Trypan Blue exclusion test and in vivo by the Galleria mellonella model. ADP/epinephrine-induced platelet aggregation after treatment with AAPO (50, 100, 200, 400, and 800 μg/mL) was evaluated by turbidimetry, and coagulation was determined by prothrombin activity time (PT) and activated partial thromboplastin time (aPTT). Platelet activation was measured by expression of P-selectin on the platelet surface by flow cytometry and intraplatelet content of reactive oxygen species (ROS) by fluorimetry. The results showed that AAPO has as major components such as oleic acid, palmitic acid, lauric acid, caprylic acid, and squalene. AAPO showed no toxicity in vitro or in vivo. Platelet aggregation decreased against agonists using treatment with different concentrations of AAPO. Oil did not interfere in PT and aPTT. Moreover, it expressively decreased ROS-induced platelet activation and P-selectin expression. Therefore, AAPO showed antiplatelet action since it decreased platelet activation verified by the decrease in P-selectin expression as well as in ROS production.

A case of varicose necrotic phlegmon of the orbit in a child

AIM: This study aimed to analyze the peculiarities of a clinical case of orbital cellulitis in a child with varicella-zoster virus infection. MATERIAL AND METHODS: In this report of a rare case, necrotizing orbital cellulitis developed on day 6 from the onset of varicella-zoster disease in a 5-year-old child. The child was hospitalized in a serious condition at the intensive care unit of an infectious disease hospital and was subsequently transferred to an ophthalmology department of another hospital. The patient was subjected to comprehensive laboratory examinations and received conservative and surgical treatments. Computed tomography was performed to detect changes in the status of the orbits. RESULTS: The disease manifested with a pronounced pain syndrome in the right orbit, intoxication, and hyperthermia. Exophthalmos, purulent discharge, and necrosis of the conjunctiva of the affected eye were also observed. Computed tomography revealed infiltration of the right orbit without changes in the sinuses. The clinical blood analysis demonstrated leukocytosis, left shift in neutrophils, eosinophilia, and high levels of C-reactive protein and lactate dehydrogenase. The coagulogram demonstrated a proclivity toward hypercoagulation, as evidenced by diminished prothrombin activity according to Quick’s test, increased active partial thromboplastin time, and high D-dimer levels. Urinalysis revealed leukocyturia. Cultures from the conjunctival cavity yielded Streptococcus pyogenes, and a polymerase chain reaction tested positive for S. pyogenes. Antiviral, antibacterial, and symptomatic treatments were initiated. Necrotic masses were obtained during the drainage of the orbital cavity. The child was hospitalized for 21 days. The symptoms were controlled, and the patient’s condition was satisfactory at discharge. Visual functions remained fully preserved. At the examination 1.5 months later, a slight residual exophthalmos was detected. CONCLUSION: Employing a complex multidisciplinary approach, timely prescription of antibacterial and antiviral therapy, and surgical assistance (drainage of the orbit) ensures a successful disease outcome.

Risk factors of acute ischemic stroke and the role of angiotensin I in predicting prognosis of patients undergoing endovascular thrombectomy.

The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk factors of AIS and explore the role of serum indicators such as angiotensin I (Ang I) in the prognosis of patients undergoing endovascular thrombectomy (EVT). Patients with AIS who underwent EVT and healthy controls were retrospectively enrolled in this study, and the patients were divided into a good or a poor prognosis group. We compared Ang I, blood routine indexes, biochemical indexes, electrolyte indexes, and coagulation indexes between patients and controls. We used univariate and multivariate logistic regression analyses to evaluate possible risk factors for AIS and the prognosis of patients undergoing EVT. Independent risk factors for the prognosis of patients undergoing EVT were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves (ROC). Consistent with previous studies, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. In addition, Ang I levels are lower in AIS compared to the controls. The level of Ang I was higher in the good prognosis group. Furthermore, we developed a nomogram to evaluate its ability to predict the prognosis of AIS after EVT. The AUC value of the combined ROC model (Ang I and albumin-globulin ratio (AGR)) was 0.859. In conclusion, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. The combined Ang I and AGR model has a good predictive ability for the prognosis of AIS patients undergoing arterial thrombectomy.

Generation of Rapid and High-Quality Serum by Recombinant Prothrombin Activator Ecarin (RAPClot™).

We recently reported the potential application of recombinant prothrombin activator ecarin (RAPClot™) in blood diagnostics. In a new study, we describe RAPClot™ as an additive to develop a novel blood collection prototype tube that produces the highest quality serum for accurate biochemical analyte determination. The drying process of the RAPClot™ tube generated minimal effect on the enzymatic activity of the prothrombin activator. According to the bioassays of thrombin activity and plasma clotting, γ-radiation (>25 kGy) resulted in a 30-40% loss of the enzymatic activity of the RAPClot™ tubes. However, a visual blood clotting assay revealed that the γ-radiation-sterilized RAPClot™ tubes showed a high capacity for clotting high-dose heparinized blood (8 U/mL) within 5 min. This was confirmed using Thrombelastography (TEG), indicating full clotting efficiency under anticoagulant conditions. The storage of the RAPClot™ tubes at room temperature (RT) for greater than 12 months resulted in the retention of efficient and effective clotting activity for heparinized blood in 342 s. Furthermore, the enzymatic activity of the RAPClot™ tubes sterilized with an electron-beam (EB) was significantly greater than that with γ-radiation. The EB-sterilized RAPClot™ tubes stored at RT for 251 days retained over 70% enzyme activity and clotted the heparinized blood in 340 s after 682 days. Preliminary clinical studies revealed in the two trials that 5 common analytes (K, Glu, lactate dehydrogenase (LD), Fe, and Phos) or 33 analytes determined in the second study in the γ-sterilized RAPClot™ tubes were similar to those in commercial tubes. In conclusion, the findings indicate that the novel RAPClot™ blood collection prototype tube has a significant advantage over current serum or lithium heparin plasma tubes for routine use in measuring biochemical analytes, confirming a promising application of RAPClot™ in clinical medicine.

Risk factors related to significant hepatic inflammation in patients with acute drug-induced liver injury

Background and aimsCurrently, research on biopsy-proven acute drug-induced liver injury (DILI) remains limited. This study aimed to identify clinical characteristics and risk factors for significant hepatic inflammation in patients with acute DILI. MethodsAn ambispective cohort study was conducted on biopsy-proven acute DILI patients admitted to our hospital from 2012 to 2018. Using the Scheuer scoring system, patients were categorized into G0-2 or G3-4 groups and followed up for 12 months after first admission. Clinical characteristics and outcomes were retrieved from medical records. ResultsThe median age of the 157 enrolled patients (65.6% female) was 40.4 (interquartile range (IQR), 31.9–49.1) years. The median latency and length of hospitalization were 30.0 (IQR, 5.0–60.0) and 18.0 (IQR, 12.0–26.0) days. The proportions of patients in the G0-2 and G3-4 groups were 54.8% and 45.2%, respectively. Logistic regression analysis revealed that females (odds ratio (OR): 2.623, 95% confidence interval (CI): 1.169–5.887, p = 0.019), higher body mass index (OR: 1.168, 95% CI: 1.029–1.325, p = 0.016), higher total bilirubin (OR: 1.004, 95% CI: 1.000–1.007, p = 0.047), and lower prothrombin activity (OR: 0.976, 95% CI: 0,957–0.995, p = 0.013) were associated with significant hepatic inflammation. The predominance of the hepatocellular injury pattern (60.5%) at admission transformed into a predominance of the cholestatic pattern (60.5%) at discharge. During follow-up, 23 patients (14.6%) developed chronic DILI, with nine patients (5.7%) progressing to cirrhosis. Moreover, 15 female patients (9.6%) developed autoimmunity (3cases in the G0-2 group vs 12 cases in the G3-4 group, p < 0.05). ConclusionAcute DILI patients with high-risk factors were more likely to develop significant hepatic inflammation, and females with significant inflammation were at a higher risk of developing autoimmunity during follow-up.

Abstract 3096: Role Of Circulating Phosphatidylserine In The Procoagulant Activity Of Amniotic Fluid

Background: Amniotic fluid (AF) embolism is one of the most catastrophic complications during pregnancy. While studies primarily attributed the procoagulability of AF to circulating tissue factor (TF), the exact mechanism remains unclear. Aims: Define the procoagulant mechanisms of AF. Methods: Clotting time assays were performed using normal human plasma or plasma depleted of factor (F)XII, XI, X, IX, VII, V, or prekallikrein (PK). Chromogenic substrate assays were used to quantify FX activation by the TF/FVIIa complex and prothrombin activation by FXa. Phosphatidylserine (PS) levels were quantified using a fluorometric kit. Results: AF shortened the clotting time of normal plasma from 572±83 to 160±2 seconds; AF-induced clotting times were equivalent for FXII, PK, FXI, FX, FIX, or FV-depleted plasma or in the presence of contact pathway inhibitors as compared to normal plasma. In contrast, the procoagulant effects of AF were diminished or absent for FVII-depleted plasma or in the presence of a blocking anti-TF antibody or low-molecular-weight heparin. In a purified system, AF reduced FX activation by the TF/FVIIa complex. The addition of a blocking anti-tissue factor pathway inhibitor (TFPI) antibody reversed the effect of AF on FX activation. Western blotting confirmed the existence of both TF and TFPI in AF. AF enhanced prothrombin activation by FXa. The addition of annexin V, or lactadherin, which bind to PS, or the use of Gla-domainless prothrombin mitigated the effect of AF on prothrombin activation. PS levels in AF and normal plasma were 811±376 and 10.4±3.8 μM, respectively. Conclusions: The procoagulability of AF is independent of the contact pathway while being sensitive to both TF and TFPI levels. Furthermore, PS in AF significantly contributes to its procoagulability. This knowledge is important when developing strategies to lessen the procoagulability of AF without compromising hemostasis in the setting of AF embolism-associated coagulopathy.

Serum β-klotho is a potential biomarker for the progression of hepatitis B virus-related liver diseases.

Hepatitis B virus (HBV) infection is a global epidemic that can lead to several liver diseases, seriously affecting people's health. This study aimed to investigate the clinical potential of serum β-klotho (KLB) as a promising biomarker in HBV-related liver diseases. This study enrolled 30 patients with chronic hepatitis B (CHB), 35 with HBV-related cirrhosis, 66 with HBV-related hepatocellular carcinoma (HCC), and 48 healthy individuals. ELISA measured the levels of serum KLB in the four groups. We then compared the differences in serum KLB levels among the groups and analyzed the relationship between serum KLB and routine clinical parameters. The concentrations of serum KLB levels were increased sequentially among the healthy subjects, the HBV-related CHB group, the HBV-related cirrhosis group, and the HBV-related HCC group (p < 0.05). Expression of KLB was positively correlated with alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, alkaline phosphatase, total bile acid, serum markers for liver fibrosis, ascites, cirrhosis, splenomegaly, and model for end-stage liver disease sodium, while negatively correlated with platelet count, albumin, and prothrombin activity (p < 0.05). In addition, serum KLB has better sensitivity in diagnosing HCC than AFP, and serum KLB combined with AFP has higher sensitivity and specificity than AFP alone in diagnosing HCC. Serum KLB level is associated with the severity of HBV-related liver diseases and has important diagnostic value for HCC. Therefore, it could be a predictive biomarker for monitoring disease progression.

Development and validation of a nomogram for predicting poor operative visibility during FESS in Chinese adult patients with CRS.

The purpose of this study is to develop and evaluate a nomogram that is capable of predicting poor operative visibility during functional endoscopic sinus surgery. To identify potential risk factors, patients with chronic rhinosinusitis who underwent functional endoscopic sinus surgery (FESS) between January 2019 and December 2022 were selected from our hospital's electronic medical record system. Data on general patient information, clinical manifestations, clotting-related test indices, Lund-Machay score of sinuses CT scanning, Lund-kennedy score of nasal endoscopies, anesthesia methods, intraoperative blood pressure and heart rate, and Boezaart bleeding score were collected. Minimum absolute convergence and selection operator (LASSO) regression, as well as multivariate logistic regression, were used to determine the risk factors. A nomogram was developed in order to predict poor operating visibility during FESS, and its performance was evaluated utilizing both the training and verification datasets via various measures including receiver operating characteristic (ROC) curve analysis, area under the curve (AUC), Hosmer-Lemeshow goodness-of-fit test, calibration curve, and decision curve analysis. Of the 369 patients who met the inclusion criteria, 88 of them exhibited POV during FESS. By deploying LASSO and multivariate logistic regression analyses, six risk factors were identified and used to construct a nomogram for predicting POV during FESS. These factors include prothrombin time (PT), prothrombin activity (PTA), Lund-Mackay score (LMS), Lund-Kennedy score (LKS), anesthetic method, and intraoperative hypertension. The AUC of the training set was found to be 0.820 while that of the verification set was 0.852. The Hosmer-Lemeshow goodness-of-fit test and calibration curve analysis revealed good consistency between predicted and actual probabilities. Also, the decision curve demonstrated that the nomogram had a high degree of clinical usefulness and net benefit. The constructed nomogram has a strong ability to predict the poor intraoperative field in patients with chronic rhinosinusitis, which can help preoperative judgment of high-risk patients and provide evidence for perioperative management and preoperative plan formulation.

Purification and Biochemical Characterization of a Novel Fibrinolytic Enzyme from Culture Supernatant of Coprinus comatus.

A novel fibrinolytic enzyme was produced by the liquid fermentation of Coprinus comatus. The enzyme was purified from the culture supernatant by hydrophobic interactions, gel filtration, and ion exchange chromatographies. It was purified by 241.02-fold, with a specific activity of 3619 U/mg and a final yield of 10.02%. SDS-PAGE analysis confirmed the purity of the enzyme, showing a single band with a molecular weight of 19.5 kDa. The first nine amino acids of the N-terminal of the purified enzyme were A-T-Y-T-G-G-S-Q-T. The enzyme exhibited optimal activity at a temperature of 42 °C and pH 7.6. Its activity was significantly improved by Zn2+, K+, Ca2+, Mn2+, and Mg2+ while being inhibited by Fe2+, Fe3+, Al2+, and Ba2+. The activity of the enzyme was completely inhibited by ethylenediamine tetraacetic acid (EDTA), and it was also dose-dependently inhibited by phenylmethylsulfonyl fluoride (PMSF) and soy trypsin inhibitor (SBTI). However, inhibitors such as N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK), aprotinin, and pepstatin did not significantly affect its activity, suggesting that the enzyme was a serine-like metalloproteinase. The enzyme acted as both a plasmin-like fibrinolytic enzyme and a plasminogen activator, and it also exhibited the capability to hydrolyze fibrinogen and fibrin. In vitro, it demonstrated the ability to dissolve blood clots and exhibit anticoagulant properties. Furthermore, it was found that the enzyme prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), and reduced the levels of fibrinogen (FIB) and prothrombin activity (PA). Based on these studies, the enzyme has great potential to be developed as a natural agent for the prevention and treatment of thrombotic diseases.

Development and validation of prediction model for technique failure in peritoneal dialysis patients: An observational study.

This study aimed to establish a prediction model in peritoneal dialysis patients to estimate the risk of technique failure and guide clinical practice. Clinical and laboratory data of 424 adult peritoneal dialysis patients were retrospectively collected. The risk prediction models were built using univariate Cox regression, best subsets approach and LASSO Cox regression. Final nomogram was constructed based on the best model selected by the area under the curve. After comparing three models, the nomogram was built using the LASSO Cox regression model. This model included variables consisting of hypertension and peritonitis, serum creatinine, low-density lipoprotein, fibrinogen and thrombin time, and low red blood cell count, serum albumin, triglyceride and prothrombin activity. The predictive model constructed performed well using receiver operating characteristic curve and area under the curve value, C-index and calibration curve. This study developed and verified a new prediction instrument for the risk of technique failure among peritoneal dialysis patients.

Risk Factors of Sepsis-Associated Thrombocytopenia among Patients with Sepsis Induced Coagulopathy.

The study aims to evaluate the prognosis and risk factors of sepsis-associated thrombocytopenia (SAT) among patients with coagulopathy, and to provide evidence of the relationship between adverse outcomes and potential risks. Patients with sepsis-associated coagulopathy were included in the study from January 2014 to December 2022. The primary outcome was sepsis-associated thrombocytopenia (platelet count less than 100 *109/L), which was evaluated by logistic regression models adjusted for demographic characteristics and comorbidities. Among patients in the SAT group, 54% developed severe SAT, while 16% of these patients recovered from thrombocytopenia. The in-hospital mortality rate was significantly higher in the SAT group compared to the non-SAT group (31% in SAT group vs 23.9% in non-SAT group, p = 0.029). Even after adjusting for age, gender, Charlson comorbidity, white blood cell, and Sequential Organ Failure Assessment score, the differences in mortality rate persisted (Odds Ratio 0.72, [95% Confidence Interval 0.52-0.92]). Correlation analyses revealed that prothrombin time (r = 0.08, p = 0.50), international normalized ratio (r = 0.08, p = 0.42), prothrombin activity (r = -0.06, p > 0.999), D-dimer (r = -0.02, p > 0.999), and inflammatory parameters such as C-reactive protein (r = -0.11, p = 0.37) were not significantly correlated with platelet counts. According to subgroup analyses, patients with lung infection complicated by SAT had slightly higher mortality (OR 0.66, [95% CI, 0.46 to 0.94]). Sepsis-associated coagulopathy indicates a subset of critical ill patients, with those experiencing thrombocytopenia at greater risk for in-hospital death compared to those without it.