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Background: Impaired thrombin generation (TG) in patients with acquired coagulop-athy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet-depend-ent TG over and above that of simple replacement therapy.Objective: To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia.Methods: TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20-300 × 109/L) were spiked with PCCs (25%-150% increase in plasma PCC levels).Results: PCCs and platelets significantly increased TG in a dose-dependent manner in vitro. Two-way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combi-nation with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG.Conclusions: Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to mod-erate thrombocytopenia and abnormal coagulation, Objective: To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia., Methods: TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20-300 × 109/L) were spiked with PCCs (25%-150% increase in plasma PCC levels)., Results: PCCs and platelets significantly increased TG in a dose-dependent manner in vitro. Two-way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combi-nation with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG., Conclusions: Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation., peer-reviewed

Introduction Recruitment to perioperative randomised controlled trials is known to be challenging. Qualitative methods offer insight into barriers and enablers to participation. This is a substudy within a feasibility randomised controlled trial of octreotide infusion during liver transplantation at two National Health Service hospitals, which will evaluate patient and staff experiences of trial processes. By sharing formative understanding from these methods with the trials team we aim to improve staff–patient interactions and hence recruitment rates. Methods and analysis This prospective mixed-methods study will comprise two workstreams. First, after consent to the randomised controlled trial is sought, all patients will be invited to complete a questionnaire to explore their perceptions of the information given to them and motivating factors that influenced their decision to consent or not. Questionnaires will be analysed using descriptive statistics and framework analysis. If the recruitment:approach ratio drops below a predetermined ratio or if there are any specific recruitment concerns from the trials team, a second workstream involving mixed-methods fieldwork will be implemented. This will involve audiorecording of recruitment consultations and a follow-up semistructured interview to explore patients’ perception of their decision-making regarding recruitment. Semistructured interviews will also be conducted with the recruitment team to establish their views about the trial, barriers to recruitment and ways to overcome them. Recruitment consultations will be analysed using Q-QAT methodology and interviews will be analysed using framework analysis. Findings from both workstreams will be formatively fed back to the trials team to enable iterative improvement to recruitment processes. Ethics and dissemination Approval has been granted by Greater Manchester West Research Ethics Committee (ref 20/NW/0071), the Health Research Authority and the local Research and Development offices. A manuscript detailing the summative findings will be submitted to peer-reviewed journals. Trial registration number NCT04941911.

The Baveno VI guidelines propose that cirrhotic patients with a liver stiffness measurement (LSM)20kPa and a platelet count150,000/μl can avoid screening endoscopy as their combination is highly specific for excluding clinically significant varices. The aim of the study was to validate these criteria.Transient elastography data was collected from two institutions from 2006-2015. Inclusion criteria were a LSM ⩾10kPa and an upper gastrointestinal endoscopy within 12months, with a diagnosis of compensated chronic liver disease. Exclusion criteria were porto-mesenteric-splenic vein thrombosis and non-cirrhotic portal hypertension. Varices were graded as low risk (grade2) or high risk (grade ⩾2).The study included 310 patients (169 (55%) hepatitis C, and 275 (89%) Child-Pugh A). Varices were present in 23% cases, with 5% prevalence of high risk varices. Overall 102/310 (33%) met the Baveno VI criteria. Within this group 11% had varices and 2% had high risk varices, representing 2/15 (13%) of all high risk varices. The Baveno VI criteria gave a sensitivity 0.87, specificity 0.34, positive predictive value 0.06, negative predictive value 0.98, positive likelihood ratio 1.31 and negative likelihood ratio 0.39. The AUROC for LSM and platelet count combined was 0.746.The Baveno VI criteria performed well correctly identifying 98% of patients who could safely avoid endoscopy.This study examines the effectives of a recent set of guidelines published by the Baveno VI conference, which states that patients with chronic liver disease and a low liver stiffness (20kPa) and high platelet count (150) are at low risk of having varices and do not need a screening endoscopy. Varices are a complication of cirrhosis, confer a risk of serious bleeding, and can be diagnosed and treated by endoscopy. Our study reviewed the clinical records of patients who have had liver stiffness scans and endoscopy over a 9-year period at two hospitals. The results show that only about 2% of patients who meet the Baveno VI criteria will be miss-classified as not having varices.