•To date most reports on COVID-19 associated coagulopathy focused an increased activation of the plasmatic coagulation system.•Using a novel method to assess clot lysis we observed abnormalities in fibrinolysis in COVID-19 infection.•Our finding suggests that fibrinolysis system may contribute to the procoagulatory status in COVID-19 patients.

UNASSIGNED: Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis.
UNASSIGNED: Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models.
UNASSIGNED: A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis.
UNASSIGNED: An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients.
UNASSIGNED: Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin.
UNASSIGNED: UME-ID-10042.

According to the ICH S3A Q&A, microsampling is applicable to pharmaceutical drugs and toxicological analysis. Few studies have reported the effect of microsampling on the toxicity of immunotoxicological drugs. The aim of this multicenter study was to evaluate the toxicological effects of serial microsampling on rats treated with azathioprine as a model drug with immunotoxic effects. Fifty microliters of blood were collected from the jugular vein of Sprague-Dawley rats at six time points from day 1 to 2 and 7 time points from day 27 to 28. The study was performed at three organizations independently. The microsampling effect on clinical signs, body weights, food consumption, hematological parameters, biochemical parameters, urinary parameters, organ weights, and tissue pathology was evaluated. Azathioprine-induced changes were observed in certain hematological and biochemical parameters and thymus weight and pathology. Microsampling produced minimal or no effects on almost all parameters; however, at 2 organizations, azathioprine-induced changes were apparently masked for two leukocytic, one coagulation, and two biochemical parameters. In conclusion, azathioprine toxicity could be assessed appropriately as overall profiles even with blood microsampling. However, microsampling may influence azathioprine-induced changes in certain parameters, especially leukocytic parameters, and its usage should be carefully considered.

UNASSIGNED: During percutaneous transluminal coronary angioplasty (PTCA), activated clotting time (ACT) measurements are recommended to attest a correct anticoagulation level and, if needed, to administer further unfractionated heparin (UFH) to obtain a therapeutic ACT value. Our clinical routine led us to observe that smokers had lower ACT values after standardized UFH administration during PTCA. Procoagulant status in smokers is well documented.
UNASSIGNED: To determine whether tobacco negatively affects UFH anticoagulation during PTCA when evaluated by ACT.
UNASSIGNED: The ACT-TOBACCO trial is a single-center, noninterventional, prospective study. The primary end point is the comparison of ACT values after standardized UFH administration between active smokers and nonsmokers (active smoker group vs nonsmoker group) requiring coronary angiography followed by PTCA. The main secondary end points include ACT comparison after the first and second standardized UFH administration according to the patient\'s smoking status (active, ex-, or nonsmoker) and the clinical presentation of ischemic cardiomyopathy: stable (silent ischemia or stable angina) or unstable (unstable angina or acute coronary syndrome without or with ST-segment elevation).
UNASSIGNED: To the best of our knowledge, ACT values during PTCA between smokers and nonsmokers have not previously been compared. As current PTCA procedures increase in complexity and duration, the understanding of procoagulant risk factors such as smoking and the need for reliable anticoagulation monitoring becomes essential to balance hemorrhagic risk against thrombotic risk.

Reports about the impact of Carbon tetrachloride (CCl4) hepatotoxicity on coagulation profile have been inconsistent. Multiple investigators have however demonstrated the effectiveness of silymarin in the resolution of anomalies induced by CCl4, although the effect of silymarin on the impact of CCl4 hepatotoxicity, especially coagulation profile and osmotic fragility have not been investigated. The liver, the primary site for the secretion of coagulation proteins, can become impaired in CCl4 hepatotoxicity, and silymarin reportedly increases hepatic protein synthesis as part of its hepatoprotective mechanism. This study assessed the effect of silymarin on blood coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in rats. Twenty male Wistar rats were allocated into four groups (n = 5) at random, namely: Control, CCl4 given CCl4 (1 ml/kg) administered intraperitoneally twice a week, Silymarin (S) given silymarin (100 mg/kg/day) orally, and S+CCl4 given silymarin (100 mg/kg/day) orally and (1 ml/kg) CCl4 one hour after, intraperitoneally twice a week for a duration of four weeks. Results showed protraction of activated partial thromboplastin time and thrombin time, increased erythrocyte osmotic fragility, liver damage, dyslipidemia, oxidative stress and lipid peroxidation in rats given CCl4. Silymarin attenuated most of these effects as observed from comparison between CCl4 and S+CCl4 rats. The findings of this study suggests that pretreatment with silymarin attenuated disruption in coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in Wistar rats.

Steady-calcium formula (SCF), a functional food mixture with potential of joint care, contains five major ingredients. However, the uncertain cross-reactivity among these included ingredients cannot be excluded. Hence, it is important to ensure the safety of this mixture. In this study, the safety of SCF was evaluated through in vitro genotoxicity assessment and 28-day oral toxicity study in rats. The bacterial reverse mutation test and mammalian chromosome aberration test displayed that SCF did not induce mutagenicity and clastogenicity. The 28-day repeated dose assessment of SCF in rats revealed no mortality and adverse effects in clinical signs, body weight, urinalysis, hematology, organ weight, and histopathology at all treated groups. Although some significant changes were observed in food intake and parameters of serum biochemistry at the highest dose in males, they were not dose-related and considered to be within normal range. These findings indicate that SCF does not possess genotoxic potential and no obvious evidence of subacute toxicity. These results demonstrate for the first time that the genotoxicity and subacute toxicity for SCF are negative under our experimental conditions and the no observed adverse effect level (NOAEL) of SCF may be defined as at least 5470 mg/kg/day.

UNASSIGNED: Extracorporeal membrane oxygenation (ECMO) carries a high morbidity of acute brain injury (ABI) with resultant mortality increase. Transcranial Doppler (TCD) allows real-time characterization of regional cerebral hemodynamics, but limited data exist on the interpretation of microembolic signals (MES) in ECMO.
UNASSIGNED: This prospective cohort study was conducted at a single tertiary care center, November 2017 through February 2022, and included all adult patients receiving venoarterial (VA) and venovenous (VV) ECMO undergoing TCD examinations, which all included MES monitoring.
UNASSIGNED: Of 145 patients on ECMO who underwent at least 1 TCD examination, 100 (68.9%) patients on VA-ECMO received 187 examinations whereas 45 (31.1%) patients on VV-ECMO received 65 examinations (P = .81). MES were observed in 35 (35.0%) patients on VA-ECMO and 2 (4.7%) patients on VV-ECMO (P < .001), corresponding to 46 (24.6%) and 2 (3.1%) TCD examinations, respectively. MES were present in 29.4% of patients on VA-ECMO without additional cardiac support, compared with 38.1% with intra-aortic balloon pump and 57.1% with left ventricular assist device, but these differences were not statistically significant (P = .39; P = .20, respectively). Presence or number of MES was not associated with VA-ECMO cannulation mode (23.4% MES presence in peripheral cannulation vs 25.8% in central cannulation, P = .80). In both VA- and VV-ECMO, MES presence or number was not associated with presence of clot or fibrin in the ECMO circuit or with any studied hemodynamic, laboratory, or ECMO parameters at the time of TCD. ABI occurred in 38% and 31.1% of patients on VA- and VV-ECMO, respectively. In multivariable logistic regression analyses, neither ABI nor a composite outcome of arterial thromboembolic events was associated with presence or number of MES in VA- ECMO.
UNASSIGNED: TCD analysis in a large cohort of patients on ECMO demonstrates a significant number of MES, especially in patients on VA-ECMO with intra-aortic balloon pump, and/or left ventricular assist device. However, clinical associations and significance of TCD MES remain unresolved and warrant further correlation with systematic imaging and long-term neurologic follow-up.

UNASSIGNED: Standard coagulation tests such as prothrombin time, activated partial thromboplastin time, and international normalized ratio are determined by liver-synthesized coagulation factors. Despite an increased international normalized ratio, patients with cirrhosis are in a \"rebalanced\" state of hemostasis as the concomitant effect of reduced protein C, protein S, and thrombomodulin is not evaluated in standard coagulation tests. The cell-based model of hemostasis indicates additional mechanisms such as systemic inflammation, sepsis, and organ failures tip the delicate coagulation balance to an anticoagulant type in acute-on-chronic liver failure. In acute liver failure, thrombin generation and platelet function remain intact despite a marked prolongation in prothrombin time. We aimed to explain the principles, application, and utility of viscoelastic tests such as thromboelastography, rotational thromboelastometry, and Sonoclot.
UNASSIGNED: We reviewed the available literature from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trial with the search terms \'coagulation\', \'cirrhosis\', \'acute-on-chronic liver failure\', \'thromboelastography\', \'thromboelastometry\' and \'sonoclot\' for cross sectional studies, cohort studies and randomized trials.
UNASSIGNED: The point-of-care viscoelastic tests provide actionable targets for correcting the coagulation defect in a patient with bleeding and provide evidence-based algorithms for use in liver disease. A limitation of these tests is the inability to assess vessel injury and endothelial elements.
UNASSIGNED: Global coagulation tests provide a comprehensive estimate of coagulation in vitro; however, their use has only been validated in the setting of liver transplantation. Newer guidelines for hemostatic resuscitation are now accepting these POC tests, but additional data are required to validate their use as standard of care.

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient\'s condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as \'probable\' on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.

A ninety-day oral toxicity study of saponified Capsicum annum fruit extract with 50% (w/w) capsanthin (SCFE-50 C) was performed by oral gavage administration to male and female Sprague-Dawley (SD) rats at doses of 0, 500, 1000 and 2000 mg/kg BW/day for a period of ninety consecutive days. To assess the reversal of toxicity, the treatment phase was followed with a twenty-eight-day recovery period. The treatment with SCFE-50 C in both male and female SD rats showed no mortality, and no treatment-related toxicologically significant changes were observed in any groups. No significant differences between treated and control groups were found in feed consumption, body weight gain, individual organ weights, ocular examination, clinical chemistry or blood biochemistry. The necroscopy and histopathology examination did not reveal any clinically significant changes in male and female rats from the 2000 mg/kg BW/day group. According to this study, the no observable adverse effect level (NOAEL) for saponified Capsicum annum fruit extract with 50% (w/w) capsanthin (SCFE-50 C) administered by oral gavage for 90-days is > 2000 mg/kg BW/day in SD rats.