Prevalence of Bleeding and Thrombosis in Critically Ill Patients with Chronic Liver Disease

INTRODUCTION:  Hemorrhage and venous thromboembolism (VTE) are recognized complications of chronic liver disease (CLD), but their prevalence and risk factors in critically ill patients are uncertain. PATIENTS AND METHODS:  We studied a retrospective cohort of patients with CLD nonelectively admitted to a specialist intensive care unit (ICU) determining the prevalence and timing of major bleeding and VTE (early, present on admission/diagnosed within 48 hours; later, diagnosed >48 hours post-ICU admission). Associations with baseline clinical and laboratory characteristics, multiorgan failure (MOF), blood product administration, and mortality were explored. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS:  Of 623 patients with median age 52, bleeding (>48 hours after admission) occurred in 87 (14%) patients. Bleeding was associated with greater illness severity and increased mortality. Gastrointestinal bleeding accounted for 72% of events, secondary to portal hypertension in >90%. Procedure-related bleeding was uncommon. VTE occurred in 125 (20%) patients: early VTE in 80 (13%) and involving the portal vein in 85%. Later VTE affected 45 (7.2%) patients. Hepatocellular carcinoma (HCC) and nonalcoholic liver disease were independently associated with early VTE (OR: 2.79, 95% CI: 1.5-5.2 and OR: 2.32, 95% CI: 1.4-3.9, respectively), and HCC, sepsis, and cryoprecipitate use with late VTE (OR: 2.45, 95% CI: 1.11-5.43; OR: 2.26, 95% CI: 1.2-4.3; and OR: 2.60, 95% CI: 1.3-5.1). CONCLUSION:  VTE was prevalent on admission to critical care and less commonly developed later. Bleeding was associated with MOF and increased mortality. Severe MOF was not associated with an increased rate of VTE which was linked with HCC, and specific etiologies of CLD

Efficacy of pro- and anticoagulant strategies in plasma of patients undergoing hepatobiliary surgery

BACKGROUND: In vitro efficacy of pro- and antihemostatic drugs is profoundly different in patients with compensated cirrhosis and in those who have cirrhosis and are critically ill. OBJECTIVES: Here we assessed the efficacy of pro- and anticoagulant drugs in plasma of patients undergoing hepato-pancreato-biliary (HPB) surgery, which is associated with unique hemostatic changes. METHODS: We performed in vitro analyses on blood samples of 60 patients undergoing HPB surgery and liver transplantation: 20 orthotopic liver transplantations, 20 partial hepatectomies, and 20 pylorus-preserving pancreaticoduodenectomies. We performed thrombin generation experiments before and after in vitro addition of fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), low molecular weight heparin (LMWH), unfractionated heparin, dabigatran, and rivaroxaban. RESULTS: We showed that patients undergoing HPB surgery are in a hypercoagulable state by thrombin generation testing. FFP and rFVIIa had minimal effects on thrombin generation, whereas PCC had a more pronounced procoagulant effect in patients compared with controls. Dabigatran showed a more pronounced anticoagulant effect in patients compared with controls, whereas rivaroxaban and LMWH had a decreased anticoagulant effect in patients. CONCLUSION: We demonstrate profoundly altered in vitro efficacy of commonly used anticoagulants, in patients undergoing HPB surgery compared with healthy controls, which may have implications for anticoagulant dosing in the early postoperative period. In the correction of perioperative bleeding complications, PCCs appear much more potent than FFP or rFVIIa, and PCCs may require conservative dosing and caution in use in patients undergoing HPB surgery

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Improving Concordance Between Clinicians With Australian Guidelines for Bowel Cancer Prevention Using a Digital Application: Randomized Controlled Crossover Study

BackgroundAustralia’s bowel cancer prevention guidelines, following a recent revision, are among the most complex in the world. Detailed decision tables outline screening or surveillance recommendations for 230 case scenarios alongside cessation recommendations for older patients. While these guidelines can help better allocate limited colonoscopy resources, their increasing complexity may limit their adoption and potential benefits. Therefore, tools to support clinicians in navigating these guidelines could be essential for national bowel cancer prevention efforts. Digital applications (DAs) represent a potentially inexpensive and scalable solution but are yet to be tested for this purpose. ObjectiveThis study aims to assess whether a DA could increase clinician adherence to Australia’s new colorectal cancer screening and surveillance guidelines and determine whether improved usability correlates with greater conformance to guidelines. MethodsAs part of a randomized controlled crossover study, we created a clinical vignette quiz to evaluate the efficacy of a DA in comparison with the standard resource (SR) for making screening and surveillance decisions. Briefings were provided to study participants, which were tailored to their level of familiarity with the guidelines. We measured the adherence of clinicians according to their number of guideline-concordant responses to the scenarios in the quiz using either the DA or the SR. The maximum score was 18, with higher scores indicating improved adherence. We also tested the DA’s usability using the System Usability Scale. ResultsOf 117 participants, 80 were included in the final analysis. Using the SR, the adherence of participants was rated a median (IQR) score of 10 (7.75-13) out of 18. The participants’ adherence improved by 40% (relative risk 1.4, P<.001) when using the DA, reaching a median (IQR) score of 14 (12-17) out of 18. The DA was rated highly for usability with a median (IQR) score of 90 (72.5-95) and ranked in the 96th percentile of systems. There was a moderate correlation between the usability of the DA and better adherence (rs=0.4; P<.001). No differences between the adherence of specialists and nonspecialists were found, either with the SR (10 vs 9; P=.47) or with the DA (13 vs 15; P=.24). There was no significant association between participants who were less adherent with the DA (n=17) and their age (P=.06), experience with decision support tools (P=.51), or academic involvement with a university (P=.39). ConclusionsDAs can significantly improve the adoption of complex Australian bowel cancer prevention guidelines. As screening and surveillance guidelines become increasingly complex and personalized, these tools will be crucial to help clinicians accurately determine the most appropriate recommendations for their patients. Additional research to understand why some practitioners perform worse with DAs is required. Further improvements in application usability may optimize guideline concordance further

Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay

Background and Aims Patients with cirrhosis have a rebalanced hemostasis, often with normal or elevated thrombin-generating (TG) capacity in plasma. Whole blood (WB) TG allows faster determination and, importantly, includes the influence of all circulating blood cells. We aimed to study the TG profile of patients with cirrhosis in WB and in platelet poor plasma. Methods Thrombin-generating capacity in WB and plasma were assessed with a near-patient WB-TG assay and the calibrated automated thrombinography assay, respectively. TG assays were tested in presence and absence of thrombomodulin. Conventional coagulation tests were also performed. Results Thirty-four patients with cirrhosis and twenty-two controls were analyzed. Compared with controls, patients had substantially deranged results in conventional coagulation tests. Comparable WB-TG capacity (endogenous thrombin potential until peak, ETPp) but significantly lower peak thrombin were found in patients, and these results persisted when thrombomodulin was present. TG of the patients was more resistant to thrombomodulin than controls in both WB and plasma, although the inhibitory effect of thrombomodulin was drastically weaker in WB than in plasma. The peak of WB-TG in patients correlated moderately with their hematocrit and platelet count. Significant correlations were found between TG results in WB and plasma. Conclusions The WB-TG assay shows a normal to hypocoagulable state in patients with cirrhosis with a decreased anticoagulant activity of TM compared to plasma-TG. The clinical value of this assay needs further validation