Prothrombin Time Research Articles

Coagulation profiles and percentiles in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: A step toward more accurate transfusion thresholds.

In the literature, there are no studies about the transfusion threshold for neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). In order to facilitate accurate interpretation of coagulation results in these neonates, we aimed to generate specific reference intervals in this specific population. This retrospective study included all HIE neonates admitted from 2014 to 2022 to undergo TH. All infants during TH underwent blood exams, including the coagulation profile. Our primary outcome was to assess the estimates of the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles for each parameter on admission (before transfusion). By the receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) and the best cut-off point were used to evaluate the ability of the prothrombin time expressed as international normalized ratio (PT-INR) to predict the risk of any bleeding. A total of 143 infants were included in this study. On admission, the median fibrinogen value was 205mg/dL, prothrombin time 18.6seconds, PT-INR 1.50, activated partial thromboplastin time 38.3seconds, thrombin time 18.6seconds, antithrombin 57.0%. The optimal cut-off of PT-INR in predicting the risk of any bleeding was greater than 1.84 (AUC.623, p=.024). For the first time, we proposed the percentiles of coagulation parameters in our cohort of neonates with HIE. Furthermore, we found that a PT-INR greater than 1.84 can significantly predict the risk of any bleeding. Further studies are needed to determine if a restrictive versus a liberal transfusion approach can be equally safer for these high-risk infants.

Impact of Banhabaekchulcheonmatang (Banxia Baizhu Tianma Tang) and Hwangryeonhaedoktang (Huang Lian Jie Du Tang) on edoxaban: Herb-drug interaction study in healthy subjects

Ethnopharmacological relevanceConcurrent use of traditional herbal medicines and conventional drugs, particularly for stroke treatment, is widespread, raising concerns about potential drug interactions. Aim of the studyThis clinical study aimed to investigate interactions between edoxaban, a direct oral anticoagulant, and two traditional herbal medicines commonly used for stroke: Banhabaekchulcheonmatang (BBCT) and Hwangryeonhaedoktang (HRHDT). Materials and methodsKorean healthy volunteers participated in a randomized, open-label, three-period, three-treatment, two-sequence clinical study. Treatments consisted of a single oral dose of edoxaban tablet (60 mg) in the presence or absence of multiple doses of BBCT or HRHDT three times daily for six days. Pharmacokinetic and pharmacodynamic parameters of edoxaban and its active metabolite M4 were assessed following administration of edoxaban alone or in co-administration with BBCT or HRHDT. ResultsWhen edoxaban was co-administered with BBCT or HRHDT, the area under the curve (AUC) of edoxaban remained unaffected. However, its peak concentrations (Cmax) were decreased by 18.5%–28.1%. Similarly, co-administration of edoxaban with BBCT or HRHDT slightly decreased the AUC of M4 and reduced its Cmax by 16.8%–27.1%. Results revealed that BBCT and HRHDT had a minor impact on pharmacokinetics of edoxaban and M4. Despite alterations in systemic exposures, all pharmacodynamic parameters of edoxaban derived from activated partial thromboplastin time and prothrombin time were equivalent irrespective of herbal medicine co-administration. ConclusionsThese findings contribute to our understanding of potential interactions between conventional anticoagulants and traditional herbal medicines, highlighting the need for comprehensive evaluation in clinical practice.

Nrf2 Ameliorates Atrial Fibrosis During Antithrombotic Therapy for Atrial Fibrillation by Modulating CYP2C9 Activity.

Anticoagulant therapy can significantly reduce the incidence of stroke and peripheral embolism events in patients with atrial fibrillation (AF). Although warfarin is widely used as an anticoagulant drug, a wrong dose can lead to increased risks of bleeding or blood clots. The aim of this study was to assess whether nuclear factor-erythroid-2-related factor 2 (Nrf2) can improve the efficacy of warfarin through the regulation of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) using a rat model of AF. Results showed that AF significantly reduced Nrf2 in myocardial tissue of sham-operated rats. Furthermore, Nrf2 overexpression effectively reduced AF-induced atrial fibrosis by reducing collagen in the left atrium, inhibiting the expression of the fibrosis-related genes collagen I and transforming growth factor-β1 in rats with AF. Nrf2 overexpression can activate CYP2C9, decrease the serum concentration of warfarin, and decrease prothrombin time and international normalized ratio in AF rats. In this article, Nrf2 overexpression protects against fibrosis, increased survival in AF rats, and activated CYP2C9 expression, thus broadening the therapeutic range of warfarin in AF rats.

Phosphatidylserine-blocking nanoparticles inhibit thrombosis without increased bleeding in mice

BackgroundPhosphatidylserine (PS) is a procoagulant phospholipid enriched on surfaces of activated vascular cells including platelets, endothelium, monocytes, and microvesicles. As a molecular driver of thrombosis accessible to drug blockade, PS is an attractive pharmacologic target for modulating thrombogenesis, with potentially reduced bleeding risk compared to anticoagulant and antiplatelet therapies. ObjectivesTest antithrombotic capabilities of a liposomal formulation, Zn-dipicolylamine cyanine-3[22,22]/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (molar ratio, 3:97), designated as DPAL, which we previously described binds selectively to PS-enriched cell surfaces, compared with effects on bleeding, in mouse models. MethodsPS-dependent DPAL binding to human and murine platelets was tested in vitro. Thrombosis and bleeding after DPAL intravenous administration were tested in C57Bl/6J mice following FeCl3 carotid arterial injury and tail tip amputation, respectively. Incorporation in hemostatic clots was investigated in the cremaster muscle laser injury model. Toxicity was tested by direct exposure to human endothelial cell cultures. ResultsDPAL bound agonist-stimulated, PS-positive human and murine platelets, blocked by Annexin V or Ano6 deletion, which ablate PS exposure. DPAL prolonged prothrombin time, but did not prevent thrombin-induced fibrinogen receptor activation or aggregation, nor alter blood cell counts including platelets. Following arteriolar laser injury, DPAL bound wound surfaces and edges without destabilizing plugs. DPAL dose-dependently blocked FeCl3-induced arterial thrombosis but did not substantially increase bleeding, or induce endothelial cell death. ConclusionDPAL reduces thrombogenesis with minimal effects on bleeding in mouse models via selective binding to PS. DPAL may support novel approaches to modulate pathogenic thrombin generation with improved safety profiles in multiple contexts.

Assessments of coagulation profile among good glycemic control and poor glycemic control type 2 diabetic patient attending at Wolkite University specialized hospital, Central Ethiopia: a comparative study

IntroductionDiabetes Mellitus (DM) is a worldwide health issue that is defined by elevated blood glucose levels and impaired metabolism of fat, carbohydrates, and proteins. Atherosthrombotic events are very likely to occur in patients with diabetes mellitus. This results in the development of both microvascular and macrovascular complications.ObjectiveTo compare the coagulation profile parameters between patients with good glycemic control and poor glycemic control and to evaluate the association of coagulation profile and glycemic control in type 2 DM patients.Materials and methodsThis study was conducted in Wolkite university specialized hospital on 90 type 2 Diabetics patients among which 45 were with good glycemic control and 45 were with poor glycemic control. Seven ml blood samples were collected from each study participant and analyzed to assess coagulation profile including Platelet Count, activated Partial Thromboplastin Time (aPTT), and Prothrombin Time (PT). Using SPSS 21.0, an independent sample t-test was used for statistical analysis.ResultsAccording to the current study, when comparing Type 2 Diabetes with poor glycemic control to those with good glycemic control, there was an increase in PT and aPTT concentration (statistically significant, p < 0.05). The platelet counts of the two groups did not differ significantly.ConclusionPeople with Type 2 diabetes have altered coagulation profiles, which have demonstrated that hyperglycemia causes abnormalities in coagulation. Patients with Type 2 diabetes who have poor glycemic control are particularly vulnerable to atherothrombotic and hemorrhagic events. In order to prevent the onset of microvascular and macrovascular illness as soon as possible, physicians may find it helpful to evaluate the coagulation profile of diabetic patients.

Comparative Study of Coagulation Profile and Haematological Parameters in Pregnancy-Induced Hypertension (PIH).

Background Pregnancy-induced hypertension (PIH) is a major cause of maternal and fetal morbidity and mortality. PIH, including gestational hypertension, pre-eclampsia, and eclampsia, often leads to significant alterations in coagulation profiles and haematological parameters, posing risks for thromboembolic and haemorrhagic complications. This study aimed to compare the coagulation and haematological parameters between women with PIH and normotensive pregnant women. Methods A cross-sectional observational study was conducted on 110 pregnant women, divided into two groups: 55 with PIH and 55 with normotensives. Coagulation markers such as prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR), and platelet count were measured. Bleeding and clotting times were also evaluated. Data were statistically analysed using student's t-test and chi-square tests, with p ≤ 0.05 considered significant. Results Women with PIH exhibited significantly lower platelet counts, PT, aPTT, and INR values compared to the normotensive group (p < 0.0001). Thrombocytopenia and prolonged bleeding time were more common in the PIH group, suggesting an increased risk of both bleeding and clotting complications. Proteinuria was observed in 32 women (58.18%) in the PIH group, reflecting the severity of the disease. Additionally, the PIH group had markedly elevated blood pressure levels. Conclusion PIH is associated with significant coagulation and haematological abnormalities, including thrombocytopenia and a hypercoagulable state, which increase the risk of thromboembolic and hemorrhagic events. Routine monitoring of coagulation profiles and haematological parameters in PIH patients is essential for timely interventions and improving maternal and fetal outcomes.

Clinical Characteristics and Risk Factors of Sepsis in Patients with Liver Abscess.

Aims/Background Liver abscess (LA) is a serious medical condition that predisposes patients to sepsis. However, predicting sepsis in LA patients has rarely been explored. This study employed univariate and multivariate logistic regression analyses to identify independent risk factors for sepsis, which would provide guidance for clinical diagnosis and treatment. Methods A total of 122 patients with LA treated in Peking University People's Hospital from 1 January 2016 to 31 October 2022 were recruited. Among the cases, 35 patients had sepsis (sepsis group) while the remaining 87 did not have sepsis (non-sepsis group). Clinical data were collected for all enrolled cases. Univariate analysis was performed to identify potential predictors, which were tested in multivariable logistic analysis to pinpoint the independent risk factors for sepsis in LA patients; these findings were utilized to develop a prediction model. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of the prediction model. Informed consent to participate was obtained from the patients or their relatives. Results The incidence of shivering in the sepsis group was significantly higher than that in the non-sepsis group (p < 0.05). Through the univariate analysis, it was found that the reduction in platelet count and prothrombin time activity and the elevation of glycosylated hemoglobin (HbAlc) and procalcitonin (PCT) were more significant in the sepsis group than in the non-sepsis group (p < 0.05). Multivariate logistic regression analysis revealed that PCT and HbAlc were independent risk predictors of sepsis in LA patients within the derivation cohort (p < 0.05). Conclusion Elevated levels of HbAlc and PCT were independent risk factors for sepsis associated with LA. Patients with LA exhibiting elevated PCT levels demonstrated a 21% increased susceptibility to sepsis, and those with elevated HbAlc levels showed a 38% heightened risk for sepsis.

Development and validation of a prognostic score for TIPS placement in patients with viral hepatitis cirrhosis-related portal hypertension: a multi-center retrospective study.

There is no established scoring model focused on viral hepatitis patients to predict the prognosis after transjugular intrahepatic portosystemic shunt (TIPS). We aimed to develop and validate a novel model based on the largest cohort for better prediction of both short-term (1 year) and long-term (3 years) postoperative prognoses after TIPS in viral hepatitis cirrhosis-related portal hypertension patients. A total of 925 viral hepatitis cirrhosis-related portal hypertension patients who underwent TIPS from nine hospitals were divided into the training and external validation cohorts. A novel Viral-associated Index of Post-TIPS score (VIPs) model was developed after performing Cox regression analysis. The VIPs model was compared to five previous models, namely, Child-Pugh, MELD, ALBI, CCG, and FIPS. Furthermore, X-tile software was used to stratify patients into low-, medium-, and high-risk groups. The VIPs model included age, ascites, albumin, prothrombin time, total bilirubin, and sodium for post-TIPS prognosis prediction. The model demonstrated satisfying predictive efficiency in both discrimination and calibration, with an area under the curve of 0.781/0.774 (1 year/3 years) in the training cohort and 0.771/0.775 (1 year/3 years) in the external validation cohort, respectively. We first developed and externally validated a novel VIPs model for better prediction of both short-term and long-term postoperative prognoses after TIPS in Chinese patients with viral hepatitis cirrhosis-related portal hypertension.

Pre‑operative mean platelet volume is associated with overall survival in patients with IDH‑wildtype glioblastoma undergoing maximal safe resection.

Glioblastoma (GBM) is the most common, fast-growing, and aggressive malignant primary CNS tumor, with a survival time of ~15 months despite the use of surgery and adjuvant treatments. In recent years, there has been a growing interest in exploring the potential contribution of hemostasis and platelet activation in GBM biology. The present study assessed the association between the pre-operative coagulation profile [as indicated by prothrombin time (PT) ratio and activated partial thromboplastin time (aPTT) ratio], overall platelets (PLT) count and the mean platelet volume (MPV) with tumoral characteristics and overall survival in patients with isocitrate dehydrogenase-wildtype (IDH-wt) GBM.

IRON OVER LOAD AND ITS RELATION WITH HAEMOSTATIC PARAMETERS IN BETA-THALASSEMIA PATIENTS

Background: Patients with beta-thalassemia major have been observed to experience changes in their coagulation profile. These changes include an elongated prothrombin time and partial thromboplastin time as well as bring down levels of natural anticoagulants and coagulation factors. The mechanisms underlying the occurrence of thrombotic tendencies in some thalassemia patients remain unclear. This study aims to examine the alterations in the iron and coagulation profile among beta-thalassemia patients. Methods: After informed consent, 50 children having beta-thalassemia, and 50 healthy controls were included in this study. Blood samples were collected and serum ferritin, haematological and haemostatic parameters were measured. Data was analysed on SPSS-24. Results: The laboratory assessment revealed 43.5% of the patients had thrombocytopenia, 54% had prolonged prothrombin time (PT), and 56% of the patients had prolonged activated partial thromboplastin time (aPTT). All estimated coagulation factors exhibited lower activity levels in comparison to the control group. Serum ferritin exhibited a positive relationship with PT and aPTT and a substantial negative relationship with total platelet count. Conclusion: High serum ferritin levels are associated to abnormal haemostatic parameters in thalassemia patients. Regular monitoring of serum ferritin levels is essential to ensure that thalassemia patients receive appropriate treatment and support. Pak J Physiol 2024;20(3):71–3, DOI: https://doi.org/10.69656/pjp.v20i3.1742

Comparative Analysis of Coagulation Activation in Rheumatoid Arthritis Patients Treated With TNF Inhibitors Versus JAK Inhibitors: A Prospective Study.

This study aims to investigate the activation of the coagulation system of RA patients and assess changes during anti-inflammatory treatment with tumor necrosis factor blockers (anti-TNF) and Janus kinase inhibitors (JAKi). Biomarkers for the coagulation system, including D-dimer, fibrinogen, prothrombin time, activated partial thrombin time, prothrombin fragment 1 + 2, thrombin-antithrombin complex (TAT), activated factor IX, antithrombin complex, and von Willebrand factor (vWF), were longitudinally measured in 83 RA patients treated with anti-TNF and 38 RA patients with JAKi. Data were collected at baseline, after 1, 3, and 6 months. The mean age was 57 (±14) years; 76% was female. The mean DAS28-CRP was 3.6 (±1.3) for anti-TNF users and 4.1 (±1.4) for JAKi users at baseline and declined in both groups. Baseline coagulation markers levels were comparable between groups. In anti-TNF users, D-dimer and fibrinogen levels significantly declined (-0.31 mg/L, p = 0.01 and -0.71 g/L, p < 0.001, respectively), whereas TAT significantly increased after 6 months follow-up (1.46 μg/L, p = 0.03) and no effect on vWF (p = 0.98). In JAKi users, vWF declined significantly during the 6 months follow-up (-37.41%, p < 0.001); additionally, there were reductions of D-dimer, fibrinogen, and TAT that did not reach significance (-0.17 mg/L, p = 0.59; -0.49 g/L, p = 0.12; and 0.68 μg/L, p = 0.27, respectively). The prothrombotic tendency in active RA declined during effective treatment with both anti-TNF and JAKi. Altogether, the biomarkers used in this study suggest that an increased VTE risk in the first 6 months due to either treatment with anti-TNF or JAKi is unlikely.

High Blood Ammonia Level Is a Predictor of Medium and Large Size Esophageal Varices In Cirrhotic Patients

Background: The development of esophageal varices (EV) and rupture of them are the most serious complications of portal hypertension. Upper gastrointestinal endoscopy is the gold standard for diagnosis of EV but it is a costly and troublesome invasive procedure. To find a non-invasive method for detection of size of EV and to predict the bleeding risk is appealing and would decrease the indications cost and discomfort of upper GI endoscopy. The aim of the study is to evaluate high blood ammonia level is a predictor of medium and large size of esophageal varices in Cirrhotic patients. Methods: This was an observational Cross-sectional study conducted on 40 cirrhotic patients in Department of Gastroenterology, BSMMU using a pre-designed data collection sheet. Information about clinical profile, laboratory parameters- blood ammonia, serum bilirubin, serum albumin, prothrombin time, and ultrasonography of abdomen, endoscopy upper GIT was collected and recorded. The collected data was analyzed by computer with the help of SPSS version 22. Statistical analysis was done by using appropriate statistical tool like Chi-square test, Student’s t- test. P value &lt; 0.05 was considered as significant. Diagnostic efficacy of blood ammonia was calculated by using a value. Results: A total of 40 patients with cirrhosis. Mean age of cirrhotic patients were 47.47±12.98 years. Mean blood ammonia of small size EV of cirrhotic patients was 73.70±32.11 (μmol/L) and medium and large size EV was 118.3±38.37 (μmol/L) (P&lt; .001). At the level of 78.5 (μmol/L), sensitivity and specificity of blood ammonia was 95% and 65% respectively in detection of size of EV. Conclusion: Blood ammonia estimation could be a good tool for identifying individuals with medium and large size esophageal who will need to undergo endoscopy more frequently. Bangladesh J Medicine 2024; 35: 167-172

Study of Some Hormonal and Biochemical Parameters among Patients with Chronic Liver Diseases

It has been revealed previously that chronic liver disease (CLD) may be associated to hormonal fluctuations. The current study, therefore, aimed to evaluate some hormones in CLD patients compared with non-CLD individuals. This case control study was conducted at Gastroenterology and Hepatology Teaching Hospital, Medical city, Baghdad, Iraq during December 2021 to May 2022. One hundred and twenty male patients with CLD (age:14-75 years) and 120 control males (age: 24-70 years) were involved in this study. Serum samples were taken from all individuals and were then analysed for many tests which included hormones (Cortisol, testosterone, prolactin, insulin and thyroid stimulating hormone TSH); biochemical analysis (Prothrombin time PT, international normalized ratio INR and albumin); liver enzymes (aspartate aminotransferase AST, alanine aminotransferase ALT, alkaline phosphatase ALP and gamma glutamyl transferase (GGT)) and interleukins (Interleukin 13 IL-13 and transforming growth factor TGF). Some hormones such as cortisol, prolactin and insulin significantly increased in CLD patients while other hormones (testosterone and TSH) significantly decreased in CLD patients compared with the controls. Results also showed significant increase in liver enzymes among CLD patients. These changes in the hormones and liver enzymes levels may be related with significant increase in INR and albumin which were significantly higher in CLD patients than in the control group. Finally, IL-13 increased significantly in CLD patients while no significant differences were noticed between CLD and control regarding TGF levels. It can, therefore, be concluded that hormonal imbalance can affect people with liver conditions. and that this hormonal imbalance may be associated with high levels of liver enzymes.

Prevalence of Celiac Disease in Romania.

Celiac disease (CD) is an autoimmune disorder that targets the small intestine, triggered by the ingestion of gluten in genetically predisposed individuals, causing damage to the villi and impairing nutrient absorption. Despite increased awareness and improved diagnostic techniques, CD remains significantly underdiagnosed, with many individuals suffering from unexplained symptoms or misdiagnosed conditions. This study aims to investigate the prevalence and demographic characteristics of CD in a Romanian population using rapid diagnostic tests followed by histological confirmation. This cross-sectional study aimed to determine the prevalence of CD in Romania using the BIOHIT Celiac Quick Test among adult participants recruited from tertiary healthcare centers and medical institutions. The prevalence of CD was calculated by dividing the number of confirmed positive cases by the total number of participants, with further evaluation including endoscopy and histological examination for those with positive quick test results. To our knowledge, this is the first prospective study in Romania to assess the prevalence of CD using a serological test. Out of 713 participants from Romania, 9 tested positive for CD using a rapid diagnostic test, confirmed by histological examination, resulting in a prevalence rate of 1.26%. The mean age of the CD-positive group was significantly younger (30.3 years) compared to the general population (49.2 years), and they had a lower mean BMI (22.2 vs. 28.1). Most CD-positive patients were female (66.7%) and resided in urban areas (55.6%). Our study found the prevalence of CD in a Romanian population to be slightly higher than the global average, highlighting the effectiveness of rapid diagnostic tests followed by histological confirmation. The significant regional variability in CD prevalence suggests the need for further research into environmental, dietary, and genetic factors, along with enhanced awareness and improved diagnostic protocols to better manage and prevent long-term complications of CD.

Basic coagulation parameters and platelet count among malaria patients attending at Addis Zemen Primary Hospital, Northwest Ethiopia.

Malaria is an intravascular parasitic-related blood disease that causes bleeding, coagulopathy, and thrombocytopenia. However, limited data shows the effect of Plasmodium species infection on basic coagulation parameters and platelet count. Thus, this study aimed to assess basic coagulation parameters and platelet count among malaria patients. A cross-sectional study was conducted among 240 study participants (120 cases and 120 controls) from June 1, 2021, to February 30, 2022. A convenient sampling technique was employed to select study participants. The blood sample was collected by a trained laboratory technologist for platelet counts, prothrombin time (PT), partial thromboplastin time (PTT), international normalization ratio (INR), blood film, and serological testing. The collected data were analyzed in SPSS version 23. Data were analyzed by the Mann-Whitney U test, Kruskal Wallis H, and Spearman's rank-order correlation tests. Descriptive findings were presented through median, tables, and chart. In all cases, a P-value < 0.05 was considered statistically significant. The percentage of mild, moderate, and high malaria parasitemia levels per microliter of blood was 21.7%, 20%, and 58.3%, respectively. The overall median malaria parasitemia was 10,304 per microliter of blood. Among malaria patients, 77.5%, 61.7%, and 51.7% had prolonged PT, INR, and APTT, respectively as compared to control. Moreover, 26.7% of Plasmodium-infected participants had mild thrombocytopenia as compared to the control group (P < 0.001). The value of PT, APTT, and INR were significantly elevated, whereas the level of platelet count was inversely reduced when the malaria parasitemia level increased as compared to controls (p < 0.001).

Impact of Tigecycline on Coagulation in Severe Infections and Effect of Vitamin K1 Intervention: A Retrospective Single-Center Analysis.

BACKGROUND Tigecycline is a tetracycline antibiotic used to treat gram-positive and gram-negative bacterial infections, and bleeding is a dose-dependent adverse effect. Vitamin K1 is a fat-soluble vitamin used to treat hemorrhagic conditions. This retrospective study from a single center included 920 patients treated with tigecycline for bacterial infections between January 2017 and December 2022 and aimed to evaluate the incidence of coagulopathy and the use of vitamin K1. MATERIAL AND METHODS A total of 220 patients were included and divided into a high-dose group (100 mg, every 12 h) and normal-dose group (50 mg, every 12 h) according to the treatment dose of tigecycline. Clinical characteristics and changes in coagulation indicators during tigecycline treatment were collected. Seventy-two patients were treated with vitamin K1, and the changes in coagulation indicators before and after treatment were compared. ANOVA and t test were used to analyze the effects of different doses of tigecycline on coagulation function and the intervention of vitamin K1. RESULTS Among 920 patients, the incidence of coagulopathy was 23.91%. In both groups, coagulopathy occurred on days 5 to 7 after administration, and the high-dose group had worse coagulation function than the normal-dose group, including activated partial thrombin time, prothrombin time, and fibrinogen (P<0.05). After treatment with vitamin K1, fibrinogen increased and activated partial thrombin time and prothrombin time were shortened in both groups (P<0.05 or P<0.01). CONCLUSIONS Tigecycline caused coagulopathy with dose and time dependence. Vitamin K1 can improve tigecycline-induced coagulopathy.

Antithrombotic activity of Punica granatum, L (Pomegranate): Experimental investigation and exploration of its mechanism of action on primary and secondary hemostasis in vitro and ex vivo

Hemostasis is the physiological process that stops bleeding by forming a thrombus (or blood clot). However, the inappropriate formation of a thrombus can constitute a pathophysiological event involving the same steps as those of hemostasis. Despite some adverse effects, antithrombotic therapy remains an effective means in the prevention and treatment of thrombotic diseases. In this regard, scientific research aimed at discovering new remedies of natural origin is particularly active.This study aims to evaluate the antithrombotic activity of the aqueous extract of Punica granatum peels in vivo. To understand the mechanism of action of this activity, we will investigate primary and secondary hemostasis in vitro and ex vivo. Furthermore, we will examine its antioxidant activity, toxicity, and phytochemical composition to identify the molecules responsible for the observed effects.The antithrombotic activity is assessed in vivo using the acute pulmonary thromboembolism model in mouse. Thrombosis is induced by injecting the thrombogenic solution (epinephrine + collagen) into the lateral caudal vein. Platelet aggregation, both in vitro and ex vivo, is performed on washed platelets isolated by centrifugation from rat blood. The platelet suspension is pre-incubated with the extract for 1 min. Aggregation is triggered by adding the following agonists: ADP, thrombin, collagen, and arachidonic acid. The bleeding time is measured in the absence and presence of the extract following an apical section of the mouse tail. This time corresponds to the duration of flow between the first and last drops of blood. To evaluate plasma coagulation, activated partial thromboplastin time (aPTT) and prothrombin time (PT) were measured under conditions both with and without the extract, using appropriate reagents. Acute toxicity is conducted by administering a single oral dose of the extract to mice (5 and 10 g kg-1). Possible changes in animal behavior are observed for fifteen days. The identification of polyphenols and flavonoids is performed by High Performance Liquid Chromatography (HPLC).The results obtained show that P. granatum exerted a significant preventive antithrombotic action (80 % protection) in mice. Furthermore, the extract inhibited platelet aggregation induced in vitro by all agonists in a dose-dependent manner, prolonged bleeding time, and coagulation times in rats. The results of the ex vivo study in rats confirmed these effects. We also noted that the extract did not exhibit toxicity following administration, and HPLC analysis revealed a richness of polyphenols and flavonoids in the extract.P. granatum exhibited an interesting antithrombotic activity, which could be attributed to its antiplatelet and anticoagulant actions. The phytochemical compounds identified in this extract could, at least in part, be responsible for these effects. Therefore, the demonstrated activities of this plant on hemostasis could lead to the development of more effective remedies and represent a means of prevention against thrombotic events.

Computed tomography-based multi-organ radiomics nomogram model for predicting the risk of esophagogastric variceal bleeding in cirrhosis.

Radiomics has been used in the diagnosis of cirrhosis and prediction of its associated complications. However, most current studies predict the risk of esophageal variceal bleeding (EVB) based on image features at a single level, which results in incomplete data. Few studies have explored the use of global multi-organ radiomics for non-invasive prediction of EVB secondary to cirrhosis. To develop a model based on clinical and multi-organ radiomic features to predict the risk of first-instance secondary EVB in patients with cirrhosis. In this study, 208 patients with cirrhosis were retrospectively evaluated and randomly split into training (n = 145) and validation (n = 63) cohorts. Three areas were chosen as regions of interest for extraction of multi-organ radiomic features: The whole liver, whole spleen, and lower esophagus-gastric fundus region. In the training cohort, radiomic score (Rad-score) was created by screening radiomic features using the inter-observer and intra-observer correlation coefficients and the least absolute shrinkage and selection operator method. Independent clinical risk factors were selected using multivariate logistic regression analyses. The radiomic features and clinical risk variables were combined to create a new radiomics-clinical model (RC model). The established models were validated using the validation cohort. The RC model yielded the best predictive performance and accurately predicted the EVB risk of patients with cirrhosis. Ascites, portal vein thrombosis, and plasma prothrombin time were identified as independent clinical risk factors. The area under the receiver operating characteristic curve (AUC) values for the RC model, Rad-score (liver + spleen + esophagus), Rad-score (liver), Rad-score (spleen), Rad-score (esophagus), and clinical model in the training cohort were 0.951, 0.930, 0.801, 0.831, 0.864, and 0.727, respectively. The corresponding AUC values in the validation cohort were 0.930, 0.886, 0.763, 0.792, 0.857, and 0.692. In patients with cirrhosis, combined multi-organ radiomics and clinical model can be used to non-invasively predict the probability of the first secondary EVB.

A machine learning-based Coagulation Risk Index predicts acute traumatic coagulopathy in bleeding trauma patients.

Acute traumatic coagulopathy (ATC) is a well-described phenomenon known to begin shortly after injury. This has profound implications for resuscitation from hemorrhagic shock, as ATC is associated with increased risk for massive transfusion (MT) and mortality. We describe a large-data machine learning-based Coagulation Risk Index (CRI) to test the early prediction of ATC in bleeding trauma patients. Coagulation Risk Index was developed using continuous vital signs (VSs) available during the first 15 minutes after admission at a single trauma center over 4 years. Data to compute the CRI were derived from continuous features of photoplethymographic and electrocardiographic waveforms, oximetry values, and blood pressure trends. Two groups of patients at risk for ATC were evaluated: critical administration threshold and patients who received an MT. Acute traumatic coagulopathy was evaluated in separate models and defined as an international normalized ratio (INR) >1.2 and >1.5 upon arrival. The CRI was developed using 2 years of cases for training and 2 years for testing. The accuracy of the models is described by area under the receiver operator curve with 95% confidence intervals. A total of 17,567 patients were available for analysis with continuous VS data, 52.8% sustained blunt injury, 30.2% were female, and the mean age was 44.6 years. The ability of CRI to predict ATC in critical administration threshold patients was excellent. The true positive and true negative rates were 95.6% and 88.3%, and 94.9% and 89.2% for INR >1.2 and INR >1.5, respectively. The CRI also demonstrated excellent accuracy in patients receiving MT; true positive and true negative rates were 92.8% and 91.3%, and 100% and 88.1% for INR >1.2 and INR >1.5, respectively. Using continuous VSs and large-data machine learning capabilities, the CRI accurately predicts early ATC in bleeding patients. Clinical application may guide early hemostatic resuscitation. Extension of this technology into the prehospital setting could provide earlier treatment of ATC. Retrospective, Prognostic Study; Level III.

Fucosylated Chondroitin Sulfate from Bohadschia ocellata: Structure Analysis and Bioactivities

Fucosylated chondroitin sulfate (FCS) was prepared from Bohadschia ocellata using protease hydrolysis. The structural characteristics of FCS were confirmed through chemical composition analysis using FTIR spectroscopy, 1H NMR, and 13C NMR. FCS from B. ocellata (FCS-Bo) exhibited an average molecular weight of approximately 122 kDa. The biological activities of FCS-Bo, including anticoagulant, anti-cancer, and Protein Tyrosine Phosphatase 1B (PTP1B) inhibition, were evaluated. FCS-Bo displayed potent anticoagulant properties, markedly extending activated partial thromboplastin time, prothrombin time, and thrombin time when compared to the heparin control. In anti-cancer bioactivity research, FCS-Bo efficiently inhibited colony formation in the colon cancer cell lines HCT-116, HT-29, and DLD-1, achieving inhibition rates of up to 65%. Additionally, FCS-Bo exhibited significant inhibition of PTP1B, with an IC50 as low as 0.0326 µg/mL, suggesting its potential for improving insulin sensitivity and managing conditions such as type 2 diabetes and obesity.