Prothrombin Time Research Articles

The establishment of reference intervals for the ClotPro thromboelastometry device in healthy dogs

AbstractObjectiveTo establish reference intervals using a new point‐of‐care thromboelastometry device in dogs for the extrinsically activated test (EX‐test), intrinsically activated test (IN‐test), fibrin polymerization test (FIB‐test), ecarin test (ECA‐test), and tissue plasminogen activator test (TPA‐test) and to investigate the effects of storage time on the results.DesignProspective clinical study in 2022.SettingUniversity teaching hospital.AnimalsForty‐eight healthy privately or university‐owned dogs were prospectively enrolled and included on the basis of normal physical examination and normal baseline laboratory results (CBC, biochemistry profile, prothrombin time, and activated partial thromboplastin time [aPTT]).InterventionsAfter a 30‐minute storage time, the EX‐test, IN‐test, FIB‐test, ECA‐test, and TPA‐test were performed on citrated blood samples. To determine the effect of storage time, 11 samples had the EX‐test, FIB‐test, and IN‐test repeated 90 and 150 minutes after sample collection.Measurements and Main ResultsTen thromboelastometry parameters were evaluated for each test. Reference intervals were calculated using the robust method for parametric data, and the robust Box–Cox transformed or nonparametric methods were used for nonparametric data. Increasing storage time resulted in more hypocoagulable tracings. A correlation was found between the IN‐test and aPTT (r = 0.62, P < 0.0001). Other weak to moderate correlations were seen between thromboelastometry parameters and platelet count and hematocrit.Conclusions and Clinical ImportanceThe development of reference intervals for the thromboelastometry device allows for the clinical use of this technology. Analyzing samples after a prolonged storage time of more than 30 minutes may result in erroneous results. Results may also be affected by an abnormal hematocrit or platelet count.

Anticoagulation with warfarin for paediatric cardiac indications: a retrospective study.

Warfarin is used as anticoagulation for children for a wide range of cardiac indications but carries the disadvantage of requiring international normalised ratio monitoring and dose adjustment. Management of warfarin therapy is challenging due to its narrow therapeutic window and is further complicated in children by dietary changes, frequent illnesses, and developing systems of metabolism and haemostasis.A retrospective review was performed of patients' medical records to assess the indication for warfarin use, percentage of international normalised ratio values in target range (%ITR), and frequency of phlebotomy.Twenty-six patients were identified. The most common indication for warfarin use was in patients post-total cavo-pulmonary connection (n = 19, 73%). We demonstrated a variability in duration of warfarin therapy following total cavo-pulmonary connection (median of 11.1 months). Nineteen (73%) patients had used the CoaguChek machine for home measurement of international normalised ratio. The median frequency of phlebotomy for all indications was once every 10 days, and the median %ITR was 55.4 % (29.7-86.4%). Of note, the percentage under target range in the patients with mechanical mitral (n = 2) and aortic valves (n = 1) was found to be 23% and 33%, respectively.These data demonstrate a high frequency of international normalised ratio values outside of the target range as seen in previous studies of warfarin in children. This necessitates frequent phlebotomy and dose changes, which can have a significant effect on the quality of life of these patients and their families highlighting the need to focus on quality improvement in the area of anticoagulation in paediatric cardiac patients.

Recurrent Early Pregnancy Loss and Congenital Thrombophilia: A Prospective Study

Background/Objectives: This study aims to investigate the role of congenital single nucleotide thrombophilia in young females with early recurrent pregnancy loss (RPL). Methods: We studied 120 pregnant females with RPL and 80 matched females as a control with no RPL. Females were aged ≤ 35 years, had at least two consecutive first-trimester RPLs, and the acquired cause of RPL was excluded. A matched control group of 80 pregnant women with no RPL was studied. Coagulation tests included prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), a Factor XIII functional assay, and detecting IgM and IgG anti-beta2-Glycoprotein I (β2GPI) antibodies by an ELISA. The DNA samples were tested for Factor V Leiden, Factor II G20210A, Methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), FXIII V34L, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, endothelial protein C receptor (EPCR) A4600G, and endothelial protein C receptor (EPCR) G4678C. Results: Of the single nucleotide gene mutations investigated, the most relevant mutations were MTHFR C677T, MTHFR A1298C, heterozygous FXIII Val34Leu, and heterozygous FXIII 1694 C>T. Each of them conferred a statistically significant effect. There was a statistically significant protective role for the endothelial protein C receptor (EPCR) A2/A2, wild FXIII Val34Leu, and heterozygousFXIII1694 C>T. Conclusions: Our findings suggest the important role of congenital single nucleotide thrombophilia mutations in young Middle Eastern women with early RPL, particularly MTHFR mutations and FXIII Val34Leu. We found a protective effect of EPCR A2/A2, wild FXIIIVal34Leu, and heterozygous FXIII1694 C>T. We recommend additional studies to explore detrimental factors and protective factors.

Determination of prothrombin time by the Ovren method in recipients after liver transplantation from a donor diagnosed with brain death

Objective. To evaluate a new method for diagnosing the state of the hemostatic system in patients with hepatobiliary pathology who underwent liver transplantation from a donor diagnosed with brain death. Materials and Methods. A pilot prospective study was conducted involving 10 patients with liver cirrhosis of various etiologies who underwent liver transplantation from a donor diagnosed with brain death. Laboratory parameters of liver function were analyzed perioperatively, during the first 5 days, on the 10th and 14th day after surgery and before discharge or death. The correlation of the prothrombin time by Ovren with the prothrombin time by Quick and with the international normalization ratio was determined using the Spearman rank correlation coefficient. Values of p ˂0.05 were considered statistically significant. Results. The mean number of points on the scale for assessing the severity of liver failure (MELD) before surgery was 27.7 ± 6 (minimum – 15, maximum – 36), which corresponded to severe class C liver failure. The correlation between the value of prothrombin time according to Quick and according to Ovren, as well as between the values of the international normalized ratio and prothrombin time according to Ovren was statistically significantly negative: rs = –0.85315, p (two–sided test) = 0.00042 and rs = –0.90527, p (two–sided test) ˂0.05, respectively. The Ovren prothrombin time was 48% on the 5th day after surgery, after which the functions and reserves of coagulation normalized starting from the 10th day, which is conveniently assessed by an increase in this indicator to 74.5% and above. Conclusions. Determination of the prothrombin time by Ovren can improve the diagnosis of liver failure and monitoring of liver function recovery in patients after liver transplantation from a donor diagnosed with brain death.

Abstract A015: Validation of a cancer early-detection assay on liquid biopsies using DNA methylation

Abstract There is growing awareness of the benefits of early cancer detection. Early intervention can improve patient outcomes, leading to a reduction in the health care burden associated with cancer, and can also provide critical information for personalized treatments. Liquid biopsies enable quick, easy, non-invasive, and real-time testing that is suitable for screening and increases accessibility, particularly in developing countries. The use of epigenomic techniques, such as DNA methylation profiling, enhances the depth and breadth of screening beyond what standard genetic analysis can offer. Universal Diagnostics (UDx), a respected pioneer in the field of early cancer detection, has partnered with Hologic Diagenode, which brings 20 years of experience in epigenomics, to develop a customized early detection workflow for colorectal cancer (CRC). This analysis relies on DNA methylation biomarkers identified within cell-free DNA (cfDNA) from plasma. The UDx assay provides not only easy screening but also a more comprehensive analysis than that possible with conventional markers. Genome-wide methylation profiles from healthy individuals and cancer patients were used to identify biomarkers. These biomarker candidates were then validated for performance; the results of which are presented in this poster. Citation Format: Ekaterina Gracheva. Validation of a cancer early-detection assay on liquid biopsies using DNA methylation [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A015.

Abstract 4145883: Elevated International Normalized Ratio Is Associated with Severity of Intracerebral Hemorrhage for Patients Taking Direct Oral Anticoagulants

Introduction/Background: While the international normalized ratio (INR), a marker of functioning of the extrinsic and final common pathways of the coagulation cascade is associated with increased intracerebral hemorrhage (ICH) mortality for patients taking warfarin, it is not understood how it might be associated with outcomes in patients taking direct oral anticoagulants (DOACs), given the inconsistent and variable effect of DOACs on INR. Research Questions/Hypothesis: To determine whether INR is associated with increased ICH severity in patients with recent exposure to a DOAC. Methods/Approach: We included patients taking Apixaban or Rivaroxaban prior to acute presentation with ICH to hospitals participating in the Get With the Guidelines - Stroke registry, a nationwide quality improvement registry. The primary exposure was INR, which we modeled as a continuous variable with restricted cubic splines. The primary endpoint was stroke severity on presentation, measured by the National Institutes of Health Stroke Scale (NIHSS). Secondary endpoints included Glasgow Coma Scale (GCS) <=8 on admission, in-hospital mortality, composite of in-hospital mortality and discharge to hospice, and modified Rankin Scale (mRS) at discharge. We adjusted for key confounding factors, specifically age, sex, race/ethnicity, insurance status, and medical history, while taking into account within-hospital clustering. Results/Data: In total, 13,251 patients were included of whom 7,545 were exposed to apixaban and 5,706 were exposed to rivaroxaban. As shown in Table 1, for patients taking Apixaban, elevated INR was associated with increased likelihood of NIHSS >=21 (aOR 1.02 [95% CI 1.00-1.04, p=0.03] per 0.1 above 1.1) and in-hospital mortality (aOR 1.11 [95% CI 1.05-1.16, p<.001) per 0.1 above 1.1). For patients taking Rivaroxaban, similar trends were seen (aOR 1.21 [95% CI 1.08-1.35, p<.001] per 0.1 up to 1.2 for NIHSS >=21, aOR 1.13, [95% CI 1.09-1.16, p<.001] per 0.1 up to 1.6, for in-hospital mortality). Conclusion(s): Elevated INR at admission is associated with worsened ICH severity for patients taking Apixaban or Rivaroxaban.

Exploring the predictive value of serum lipids for short‐term prognosis in patients with acute‐on‐chronic liver failure

AbstractAimsAcute‐on‐chronic liver failure (ACLF) is defined as acute liver injury superimposed on chronic liver disease, resulting in a significantly increased short‐term mortality rate. Serum lipids are associated with the severity of liver disease and contribute to the prognostic assessment for cirrhosis and liver failure. However, the presentation of serum lipids varies in different studies, making it difficult to draw definitive conclusions. This study aimed to investigate the predictive value of serum lipids for short‐term prognosis in patients with ACLF.MethodsThis retrospective analysis was conducted using the clinical data of patients hospitalized for ACLF between January 2018 and December 2021. The collected data were subjected to Least Absolute Shrinkage and Selection Operator and logistic regression analyses to identify the independent predictors of 28‐day and 90‐day mortality. Separate regression models were developed for each identified serum lipid. These models were combined with the Model for End‐Stage Liver Disease (MELD), MELD combined with serum sodium concentration (MELD‐Na), Chronic Liver Failure Consortium Acute‐on‐chronic Liver Failure (CLIF‐C ACLF), and Chinese Group on the Study of Severe Hepatitis B‐ACLF (COSSH‐ACLF) scores to construct new models. The performance of these models was evaluated using the area under the receiver operating characteristic curve (AUC), Nagelkerke R2, Brier score, net reclassification index (NRI), and integrated discrimination improvement (IDI) to assess the prognostic ability of serum lipids.ResultsThis study included 266 patients with ACLF, of whom 25.9% (69/266) died within 28 days and 38.5% (102/265, with 1 lost to follow‐up) died within 90 days. The independent predictors of 28‐day mortality were age, the presence of overt hepatic encephalopathy at admission, high‐density lipoprotein cholesterol (HDL‐C) levels, and international normalized ratio (INR). The independent predictors of 90‐day mortality were age, albumin levels, serum creatinine levels, and INR. The comparative analysis revealed that the AUC of all other models exceeded that of HDL‐C (p < 0.001). The COSSH‐ACLF model demonstrated superior predictive ability compared with the MELD and HDL‐MELD models (p = 0.013 and 0.017, respectively). Furthermore, the HDL‐COSSH‐ACLF model exhibited a similar trend in predictive ability compared with the latter two models (p = 0.009). No significant differences were observed in the AUC performances of the other models. A comparison of NRI calculated using the cutoff values assigned by equal assignment revealed that the addition of HDL‐C improved the predictive ability of the MELD score by 4.6% (NRI = 0.0460, p = 0.036). The MELD‐Na score exhibited an 8.4% improvement (NRI = 0.0844, p = 0.047), while the COSSH‐ACLF score demonstrated a 14.4% improvement (NRI = 0.1443, p = 0.015). However, these changes did not significantly impact the capacity of the CLIF‐C ACLF score (NRI = 0.0350, p = 0.141). No significant differences were observed in the IDI comparisons between the models with different cutoff values (all p > 0.050).ConclusionsSerum HDL‐C is an independent predictor of 28‐day mortality in patients with ACLF. Although it has inferior predictive ability when considered alone, HDL‐C enhances the predictive capacity of MELD, MELD‐Na, and COSSH‐ACLF when incorporated into these models.

Microemulsion of Medicago marina Essential Oil: In Vitro Evaluation of Antimicrobial, Antibiofilm, Anticoagulant Effects, and In Silico Studies Involving Molecular Docking and ADME Prediction

This work characterizes microemulsions of Medicago marina essential oil and evaluates their antimicrobial, antibiofilm, and anticoagulant effects. Medicago marina L. aerial parts essential oil was hydro-distilled and analyzed by gas chromatography-FID and gas chromatography/mass spectrometry (GC/MS) for the first time from the Tunisian chemotype. The microemulsion was prepared using an oil/water formulation with a biopolymer (Arabic gum) and surfactant (Tween 20). Antibacterial and antifungal activities were evaluated using the microbroth dilution method, while anticoagulant activity was tested in vitro using prothrombin time (PT) and aPTT tests. Eventually, the binding affinities and molecule’s interactions of the main chemicals with the operational locations of C (30) carotenoid dehydrosqualene synthase and cytidine deaminase were explored. The essential oil contained 71 compounds of which 87.6% were identified. Major compounds were [Formula: see text]-ionone (17.67%), 1-methyleugenol (10.75%), eugenol (8.86%), [Formula: see text]-damascenone (4.33%), and [Formula: see text]-humulene (4.32%). A microemulsion with a diameter of 1.63 [Formula: see text] m, a polydispersity index of 0.17, a zeta potential of –40.8 mV and a pH of 6 was obtained and it showed the highest antibacterial potential against a multitude of microbes, with low MICs varying between 0.406 mg/mL and 3.25 mg/mL. Significant antibiofilm activity was observed with over 80% inhibition at 4 × MIC concentration. It showed better anticoagulant activity than heparin, with PT and aPTT values of 19.5 s and 57 s, respectively, at 10 mg/mL. Molecular docking showed that “([Formula: see text]-[Formula: see text]-ionone” had the highest binding scores. Notable pharmacokinetic and drug-like qualities were found in the obtained molecules after establishing ADME profiling. As a result, Medicago marina L. Essential oil microemulsion can be used in food processing as a preservative.

Anti-thrombotic Mechanisms of Echinochrome A on Arterial Thrombosis in Rats: In-Silico, In-Vitro and In-Vivo Studies.

Arterial thrombosis is one of the most significant healthcare concerns in the world. Echinochrome A (Ech-A) is a natural quinone pigment isolated from sea urchins. It has a variety of medicinal values associated with its antioxidant, anticancer, antiviral, anti-diabetic, and cardio-protective activities. The current study aims to investigate the effect and mechanism of Ech-A to inhibit thrombus formation induced by ferric chloride in rats. Twenty-four rats were assigned into four groups (n= 6); sham and thrombotic model groups were orally administered 2% DMSO, while the other groups were treated with two dosages of Ech-A (1 and 10 mg/kg, body weight). After seven days of administration, all groups were exposed to 50% ferric chloride for 10 min, except the sham group exposure to normal saline. The molecular docking showed the free binding energies of Ech-A and vitamin K (Vit. K) with Vit. K epoxide reductase were -8.5 and -9.8 kcal/mol, which confirm the antithrombotic activity of Ech-A. The oral administration of Ech-A caused a significant increase in partial thromboplastin time, prothrombin time, clotting time, platelet count, fibrinogen levels, factor VIII, glutathione reduced, catalase, nitric oxide, and glutathione S-transferase. While white blood cells count, calcium level, and malondialdehyde concentration significantly decreased. The histological examination revealed a definite improvement in the carotid and cardiac tissues in the Ech-A groups. The study results showed that Ech-A prevented thrombosis by several mechanisms, including chelating calcium ions, increasing the NO concentration, suppressing oxidative stress, and antagonizing Vit. K.

Predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma: nomograms based on deep learning analysis of gadoxetic acid-enhanced MRI.

This study aimed to develop nomograms for predicting post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC), using deep learning analysis of Gadoxetic acid-enhanced hepatobiliary (HBP) MRI. This retrospective study analyzed patients who underwent gadoxetic acid-enhanced MRI and hepatectomy for HCC between 2016 and 2020 at two referral centers. Using a deep learning algorithm, volumes and signal intensities of whole non-tumor liver, expected remnant liver, and spleen were measured on HBP images. Two multivariable logistic regression models were formulated to predict PHLF, defined and graded by the International Study Group of Liver Surgery: one based on whole non-tumor liver measurements (whole liver model) and the other on expected remnant liver measurements (remnant liver model). The models were presented as nomograms and a web-based calculator. Discrimination performance was evaluated using the area under the receiver operating curve (AUC), with internal validation through 1000-fold bootstrapping. The study included 1760 patients (1395 male; mean age ± standard deviation, 60 ± 10 years), with 137 (7.8%) developing PHLF. Nomogram predictors included sex, gamma-glutamyl transpeptidase, prothrombin time international normalized ratio, platelets, extent of liver resection, and MRI variables derived from the liver volume, liver-to-spleen signal intensity ratio, and spleen volume. The whole liver and the remnant liver nomograms demonstrated strong predictive performance for PHLF (optimism-corrected AUC of 0.78 and 0.81, respectively) and symptomatic (grades B and C) PHLF (optimism-corrected AUC of 0.81 and 0.84, respectively). Nomograms based on deep learning analysis of gadoxetic acid-enhanced HBP images accurately stratify the risk of PHLF. Question Can PHLF be predicted by integrating clinical and MRI-derived volume and functional variables through deep learning analysis of gadoxetic acid-enhanced MRI? Findings Whole liver and remnant liver nomograms demonstrated strong predictive performance for PHLF with the optimism-corrected area under the curve of 0.78 and 0.81, respectively. Clinical relevance These nomograms can effectively stratify the risk of PHLF, providing a valuable tool for treatment decisions regarding hepatectomy for HCC.

THE IMPACT OF ANTICOAGULANTS ON COAGULATION PARAMETERS IN THE TREATMENT OF PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA ASSOCIATED WITH COVID-19

The aim of the study was to evaluate the effect of anticoagulants on coagulation parameters in the treatment of patients with community-acquired pneumonia associated with coronavirus infection. Materials and methods. An open, prospective, observational study was conducted to achieve the research objectives. Between January 2021 and February 2022, 256 patients aged 40 to 65 years with community-acquired pneumonia were examined at the outpatient clinic of the Kherson City Clinical Hospital named after Athanasius and Olga Tropin of the Kherson City Council. Of these, 177 cases were associated with SARS-CoV-2, while 79 patients tested negative for coronavirus infection. Additionally, thirty-five healthy individuals were examined on an outpatient basis. After randomization, 143 hospitalized patients with severe community-acquired pneumonia associated with COVID-19 were divided into subgroups based on the anticoagulant used in their treatment regimen. The first subgroup consisted of 71 patients who received standard heparin infusions, while the second subgroup included 72 patients treated with enoxaparin. Results. The prothrombin time in the group of healthy volunteers was 12.60 [11.80; 13.30] seconds, and the median value was significantly higher by 13.5% compared to both the group of patients with community-acquired pneumonia associated with COVID-19 and the group without COVID-19 (p < 0.05). The median fibrinogen level in patients with COVID-19 and community-acquired pneumonia was 4.80 [4.50; 5.40] g/L, which did not significantly differ from the 4.60 [4.30; 5.40] g/L in the non-COVID-19 pneumonia group (p > 0.05). However, a significant difference was observed when compared to the healthy volunteer group, which had a fibrinogen level of 3.30 [2.50; 3.80] g/L (p < 0.05). After 72 hours of treatment, prothrombin time was significantly higher in the first subgroup (12.00 [11.00; 13.00] seconds) compared to the second subgroup (11.30 [10.00; 12.30] seconds) (p < 0.05). There was also a statistically significant difference in the international normalized ratio (INR) levels between the subgroups after 72 hours of treatment, with the first subgroup showing an INR of 1.20 [1.10; 1.30] U, versus 1.10 [1.00; 1.30] U in the second subgroup (p < 0.05). After 14 days of treatment, fibrinogen levels showed a statistically significant difference: 4.30 [4.10; 4.60] g/L in the first subgroup compared to 4.50 [4.30; 4.90] g/L in the second subgroup (p < 0.05). Conclusion. In patients with community-acquired pneumonia, blood coagulation parameters are disturbed, characterised by a decrease in prothrombin time and activated partial thromboplastin time, as well as an increase in total fibrinogen levels. After 72 hours, heparin demonstrated a more effective effect on prothrombin time and international normalised ratio compared to enoxaparin. When assessing the dynamics of coagulation parameters after 14 days, heparin was found as was more effective in reducing the level of total fibrinogen compared to enoxaparin.

Impact of ascites grading and non-selective β-blockers on 1-year prognosis of Acute-on-chronic liver failure

Objective: To investigate the influence of ascites grading and non-selective β- blockers (NSBBs) on the 1-year prognosis of patients with acute-on-chronic liver failure (ACLF). Methods: A total of 1 386 patients with ACLF were graded for ascites and followed up for one year. Kaplan-Meier Log-rank test and Cox regression were used for multivariate regression to analyze the effects of ascites grading and NSBBs on the 1-year prognosis of ACLF. Results: The incidence of ascites in 1 836 patients with ACLF was 77.56% on admission. Ascites grade was related to the 1-year prognosis of ACLF [log rank (Mantel-Cox) χ2=21.384, p=0.000]. Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin time activity(PTA), urea, MELD-Na score, and application of NSBBs were closely related to the 1-year prognosis of ACLF. The result of Kaplan-Meier Log-rank test for patients treated with NSBBs in the grade 2/3 ascites group suggest that NSBBs can improve the 1-year survival rate of ACLF patients with grade 2 and grade 3 ascites ( log rank (Mantel-Cox) χ2=6.113, p=0.013). Conclusions: Ascites grading and application of NSBBs can affect the 1-year prognosis of ACLF. NSBBs may be beneficial to the long-term prognosis of ACLF. Patients treated with NSBBs before the onset of ACLF should continue NSBBs treatment.

Population pharmacokinetics and pharmacodynamics of edoxaban in pediatric patients.

Edoxaban is an orally active inhibitor of activated factor X (FXa). Population pharmacokinetic (PK) and pharmacodynamic (PD) analyses were performed to characterize the PK and PK-PD relationships of edoxaban in pediatric patients to identify the covariates that may contribute to inter-subject variability in PK and PD of edoxaban in pediatric patients, and to compare the PK and PD data between pediatric and adult patients. The pediatric PK of edoxaban was best described by a two-compartment model with transit compartments, first-order oral absorption, and linear elimination. The estimated glomerular filtration rate (eGFR), body weight, and post-menstrual age were the significant covariates explaining variability in edoxaban PK among pediatric patients. A function based on renal maturation was applied to edoxaban clearance. The clearance for a 70 kg patient with an eGFR of 110 mL/min/1.73 m2 was estimated to be 42.9 L/h (CV ~ 31.8%). PK simulation showed that exposures across five pediatric age groups were comparable to that in adult patients receiving 60 mg once daily dose. The PK-PD relationship for anti-factor Xa was best fit with an Emax (8.65 IU/mL) model with an EC50 of 631 ng/mL. The PK-PD relationships for activated partial thromboplastin time and prothrombin time were best fit with linear models (slopes of 0.0467, and 0.0415 s mL/ng, respectively). In addition, due to the small number of efficacy and safety events, an exploratory analysis did not detect a correlation between efficacy events (recurrent venous thromboembolism) or safety events (clinically relevant bleeding) and edoxaban exposure.

Effect on Syndecan-1 and Hyaluronan Levels Depending on Multiple Organ Failure, Coagulopathy and Survival: An Observational Study in Major Trauma Patients

Background: Major trauma, as well as traumatic hemorrhagic shock go along with early damage to the endothelial glycocalyx (EG). Shed glycocalyx constituents can activate the innate immune system and aggravate secondary injury. Subsequently, we investigated the relationship between glycocalyx shedding and the occurrence of coagulopathy, multiple organ failure (MOF) and outcome in our cohort after severe trauma. Methods: We included multiple trauma patients, as defined by Injury Severity Score (ISS). Polytraumatized patients must have arrived in our level 1 trauma center within 60 min after trauma. Retrospectively, patients were assigned to predefined clinical conditions, based on injury severity (ISS ≥ 16 points), multiple organ failure (MOF score ≥ 6 points), need for massive transfusion (≥10 RBC units/first 24 h), coagulopathy (prothrombin time < 70% at 0 h) and survival (90-day survival). Syndecan-1 (Sdc-1) and hyaluronan (HA) plasma concentrations were evaluated immediately (0 h), 6 h and 12 h after trauma. Results: 49 patients (mean ISS 35.7 ± 12.1 SD, mean age 45.78 ± 15.6 SD) were included in this study. A total of 37 patients (75.5%) survived, while 12 patients died within the observation period of 90 days after trauma (24.5%). A total of 77% of all patients suffered multiple organ failure (MOF score ≥ 6, n = 30). Initial prothrombin time at 0 h was <70% in 31 patients. Plasma concentrations of circulating both glycocalyx constituents showed a significant increase over the first 12 h after trauma (p = 0.001; p = 0.008). Patients with multiple organ failure showed significantly increased hyaluronan concentrations at all three time points (p = 0.007/0.006/<0.001), and the syndecan-1 levels were significantly elevated 12 h after trauma in the MOF group (p = 0.01). Patients with coagulopathy on admission exhibited significantly higher hyaluronan levels at 12 h (p = 0.042). Non-survivors showed significantly increased syndecan-1 levels at 12 h after trauma (p = 0.024). Conclusions: Glycocalyx shedding occurs immediately after major trauma. Coagulopathy is associated with significantly increased plasma hyaluronan. Further, significant changes in plasma concentrations within the first 12 h help to identify subgroups at risk for developing MOF and death.

Predictive haemostatic biomarkers and transfusion efficacy, insights from fresh frozen plasma use in surgical patients, preliminary results

The aim of the study was to examine various haemostasis values to identify the most relevant biological indicators for detecting significant haemorrhage, to determine the effectiveness of fresh frozen plasma (FFP) transfusion. Our findings suggest that a low prothrombin time, elevated Von Willebrand Antigen, increased plasma fibrinogen, and reduced Ca2 + levels are associated with challenges in achieving proper haemostasis. However, measurements of factors II, V, VII, VIII, IX, X, XI, XIII, protein C, and protein S do not appear to be linked to difficulties in achieving adequate haemostasis. Additionally, the administration of FFP appears to impact factors V, VII, X, and II.Trial registration EudraCT number: 2019-002898-64.

A comprehensive evaluation system for ultrasound-guided infusion of human umbilical cord-derived MSCs in liver cirrhosis patients.

Infusion of mesenchymal stem cells (MSCs) via portal vein is one of the main ways for MSCs transplantation to treat liver cirrhosis (LC). As the tissue of LC showed diffuse fibrosis and thickened Glission sheath, the soft pig-tail catheter, or central venous catheter can not successfully insert the portal vein. Thus, our study used an improved method and performed a relatively comprehensive system to evaluate the effect for human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation. Fifteen patients with hepatitis B-related cirrhosis were enrolled in the study, and we performed hUC-MSCs transplantation via portal vein by using an 16-G needle and 0.035-inch guide wire combined with 7FR "retentional metal stiffner trocar" of pig-tail catheter under the guidance of contrast-enhanced ultrasound. Serum liver function, fibrotic indicators, tissue stiffness, coagulation function, and hemodynamics were measured at weeks 4, 12, and 24 after MSCs transplantation. Liver biopsy was performed before and 24 weeks after hUC-MSCs transplantation. After hUC-MSCs transplantation, the prothrombin time was lower than before. The levels of hyaluronic acid and IV-C(Type IV collagen) in fibrotic indicators were significantly reduced, and the Young's modulus was also decreased. Moreover, liver biopsy showed that the lytic necrosis of hepatocyte was decreased. In liver hemodynamics, the portal vein diameter was decreased after hUC-MSCs transplantation. hUC-MSCs transplantation can alleviate liver damage caused by LC. The improved "retentional metal stiffner trocar" of pig-tail catheter was safe and effective in the infusion of hUC-MSCs transplantation, which is worth promoting in clinical practice.

Analysis of ultrasound and magnetic resonance imaging characteristics of kaposiform hemangioen dothelioma

ObjectiveThe present study aims to investigate the ultrasound and magnetic resonance imaging (MRI) characteristics of kaposiform hemangioen dothelioma (KHE).MethodsA retrospective analysis was conducted on the clinical data of children diagnosed with KHE through postoperative pathology. Patients were divided into two groups: the KHE group and the KHE with Kasabach-Merritt Phenomenon (KMP) group (KMP group). Laboratory indicators, ultrasound, and MRI data were collected and analyzed statistically to summarize the imaging characteristics of the disease.ResultsThe levels of platelets and fibrinogen in the KHE group were significantly higher than those in the KMP group, while D-dimer levels, prothrombin time, and activated partial thromboplastin time were lower (P < 0.05). Ultrasound characteristics comparison revealed that lesions extending to the fat layer (42.47% vs. 54.24%) and invading the muscle layer (38.36% vs. 69.49%) were less common in the KHE group compared to the KMP group, with the lesion diameter being smaller in the KHE group (P < 0.05). The Adler grading predominantly showed Grade II (45.21%) in the KHE group, whereas Grade III (93.22%) was more prevalent in the KMP group (P < 0.05). MRI analysis indicated that the incidence of lesions invading the muscle layer and the presence of flow voids were lower in the KHE group compared to the KMP group (P < 0.05).ConclusionKHE patients with KMP exhibit lesions that are more prone to extending into the fat layer and invading the muscle layer, with larger diameters and abundant blood flow. Additionally, the MRI images of the lesions may exhibit flow voids.

An investigation into the contributing factors to survival of ARDS patients supported by veno-venous ECMO.

This study aimed to identify characteristics associated with survival during and post Extra Corporeal Membrane Oxygenation (ECMO) therapy, in patients with acute respiratory distress syndrome (ARDS) during the COVID-19 pandemic. A retrospective observational study on 94 consecutive patients with confirmed COVID-19 induced ARDS supported by ECMO was carried out 49/94 (52.7%) patients survived to hospital discharge. Non-survivors were found to have significantly (p < .05) higher: Pre-ECMO International normalized ratios (INR), carbon dioxide partial pressure (pCO2), Acute Kidney Injury (AKI) scores and blood urea levels. Also, lower pre-ECMO peak inspiratory pressures (PIP), mean arterial pressure, saturation of arterial oxygen (SaO2), blood bicarbonate levels (HCO3), blood Ph and fewer trials off ECMO with shorter combined trial off times. Patients that did not survive were more likely to have renal impairment and have received peri-ECMO haemofiltration. Poor prognosis was significantly associated with: receiving pre-ECMO nitric oxide (HR = 3.047, CI = 1.247-7.447, p = .015), renal impairment (HR = 3.023, CI = 1.586-5.763, p < .001), AKI of 2 (HR = 3.611, CI = 1.382-9.441, p = .009) or 3 (HR = 3.275, CI = 1.235-8.685, p = .017), peri-ECMO haemofiltration (HR = 2.412, CI = 1.310-4.442, p = .005) and the ABO blood group B (HR = 3.103, CI = 1.335-7.212, p = .008). pre-ECMO high CO2 (HR = 1.134, CI = 1.031-1.248, p = .010), blood lactate (HR = 1.350, CI = 1.156-1.576, p < .001), INR (HR = 2.571, CI = 1.438-4.598, p=<0.001) and lower blood Ph (HR = 0.023, CI = 0.002-0.210, p < .001). Commonly used mortality scores may not be of use in a COVID-19 cohort of ECMO patients. The initiation of ECMO needs to be implemented prior to metabolic derangements, renal and fulminant respiratory failure.

Techno-Economic Analysis of Near-Infrared (NIR) Systems at Feed Millsas a Low-Cost, High-Speed Alternative to Feed Ingredient Testing

Improperly balanced diets not only impact the quality of animal production but also the profits of a livestock operation. Typically, the nutrient and chemical content of feed ingredients and forages are determined using well-established wet chemistry tests. However, these tests can be expensive and time-consuming. Moreover, the increasing use of various by-products which are known to have large variations in chemical and nutrient content warrants a real-time on-site feed and forage testing system. Near infrared (NIR) spectroscopy systems are quick and effective on-site testing tools. While NIR systems are being adopted for on-farm or at feed mill ingredient and forage testing, little is known about the economic impacts of such an investment for a livestock or feed mill operator. This study developed a baseline model and an Excel based spreadsheet application for performing Return on Investment (ROI) analysis to determine the feasibility of using an on-farm or at feed mill NIR testing system. ROI was calculated based on the nutrient cost saved or spent determined from the difference of estimated nutrient content and actual calculated value. The findings from this study will promote low-cost alternatives for onfarm or at feed mill ingredient testing, positively impacting quality of animal products and minimizing costs.

Vesicular Carriers for Improved Oral Anticoagulation Competence of Rivaroxaban: In Vitro and In Vivo Investigation

Rivaroxaban is an anticoagulant for avoidance and therapy of thromboembolic disorders. Unfortunately, oral bioavailability of rivaroxaban is compromised with dose increments. Accordingly, the aim was to test nano-vesicular lipid systems for improved oral anticoagulation activity of rivaroxaban. Rivaroxaban loaded niosomes, bilosomes and spanlastic formulations were prepared. The prepared systems were assessed in terms of particle size, zeta potential, transition electron microscopic features (TEM), entrapment efficiency, in-vitro drug release, and in-vivo anticoagulation performance in rats. The prepared vesicular systems exposed spherical negatively charged vesicles with mean particle size values between 136.6 nm to 387.9 nm depending on the composition. Rivaroxaban was efficiently entrapped in the vesicular systems with entrapment efficiency values ranging from 92.4% to 94.0%. Rivaroxaban underwent sustained release from the fabricated vesicular systems. The in vivo performance of the tested preparation revealed significant enhancement of the anticoagulation parameters. This was manifested from the prolonged clotting time, and prothrombin time. Moreover, the cut tails of the examined rats receiving the formulated nano-systems exposed a lengthy tail bleeding time compared to those receiving the un-processed rivaroxaban aqueous dispersion. In Conclusion, niosomes, bilosomes and spanlastic nano-dispersions have a potential to overwhelm the oral anticoagulation efficiency of rivaroxaban with spanlastic ranked as best.Graphical