Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen

Patients with cirrhosis have hemostatic changes, which may contribute to a risk of thrombosis. This in vitro study compares clot formation and structure between patients and healthy subjects. Clot formation is delayed in patients; ultimately, however, clot permeability is decreased. The thrombogenic structure of fibrin clots may contribute to the thrombotic risk in cirrhosis. Background and Objectives: Patients with cirrhosis can be at risk of thrombotic complications due to an imbalance between hemostatic components. However, little is known on how the disease affects clot generation or how alterations in the structure of fibrin clots may affect the hemostatic function of these patients. Methods: We investigated the formation and structure of clots generated with plasma and purified fibrinogen of 42 patients with cirrhosis. Clots generated with plasma and fibrinogen of 29 healthy volunteers were studied for comparison. Clot formation and structure were assessed by turbidity, permeation studies, confocal laser and scanning electron microscopy (SEM). The extent of fibrinogen oxidation was assessed by measuring the carbonyl content of purified fibrinogen samples. Results: Tissue factor and thrombin-induced clotting of plasma was delayed in patients. The clotting rate was also decreased, but change in turbidity, fibrin density and fiber thickness were largely comparable to healthy volunteers. Conversely, clot permeability was significantly decreased in patients. When clots were generated with purified fibrinogen, differences in clot formation and structure similar to those in plasma were found. The carbonyl content was increased in patient fibrinogen and correlated with disease severity and clot permeability. Conclusions: Delayed clot formation in cirrhosis ultimately results in decreased clot permeability. Similar alterations in clots generated with purified fibrinogen suggest that modifications of the molecule are (partly) responsible. Taken together, these findings are indicative of hypercoagulable features of clots of patients with cirrhosis, which may explain the increased risk of thrombosis associated with this condition

Migrants’ primary care utilisation before and during the COVID-19 pandemic in England: An interrupted time series analysis

Background How international migrants access and use primary care in England is poorly understood. We aimed to compare primary care consultation rates between international migrants and non-migrants in England before and during the COVID–19 pandemic (2015–2020). Methods Using data from the Clinical Practice Research Datalink (CPRD) GOLD, we identified migrants using country-of-birth, visa-status or other codes indicating international migration. We linked CPRD to Office for National Statistics deprivation data and ran a controlled interrupted time series (ITS) using negative binomial regression to compare rates before and during the pandemic. Findings In 262,644 individuals, pre-pandemic consultation rates per person-year were 4.35 (4.34–4.36) for migrants and 4.60 (4.59–4.60) for non-migrants (RR:0.94 [0.92–0.96]). Between 29 March and 26 December 2020, rates reduced to 3.54 (3.52–3.57) for migrants and 4.2 (4.17–4.23) for non-migrants (RR:0.84 [0.8–0.88]). The first year of the pandemic was associated with a widening of the gap in consultation rates between migrants and non-migrants to 0.89 (95% CI 0.84–0.94) times the ratio before the pandemic. This widening in ratios was greater for children, individuals whose first language was not English, and individuals of White British, White non-British and Black/African/Caribbean/Black British ethnicities. It was also greater in the case of telephone consultations, particularly in London. Interpretation Migrants were less likely to use primary care than non-migrants before the pandemic and the first year of the pandemic exacerbated this difference. As GP practices retain remote and hybrid models of service delivery, they must improve services and ensure primary care is accessible and responsive to migrants’ healthcare needs

The utility of biomarkers in prognosis assessment of patients with acute liver failure

Background: Acute liver failure (ALF) is a rare but potential lethal condition characterized by the sudden development of jaundice, coagulopathy and hepatic encephalopathy in patients without underlying liver disease. In selected patients, emergency liver transplantation is required. Selection of these patients is based on clinical criteria such as the Kings College Criteria (KCC) or the Clichy criteria. Aims: The aim of this work is to provide an overview of potential biomarkers that could improve the prognostic value of KCC. Results: Several promising biomarkers involved in related pathophysiological processes have been identified. Some could be as stand-alone biomarkers; however, the best prognostic values have been observed in the combination of biomarkers with current models. Among these, the ALFSG Index that combines clinical parameters and circulating blood levels of CK18 claims a higher prognostic value than KCC. Conclusions: In this review, all potential biomarkers for ALF have been summarized to give an overview of the work performed over the last years, and a glimpse of what to expect in this field in the coming years