33 research outputs found
Reply to: plasma levels of cell-free DNA and the association with activation of coagulation prior to and during liver transplantation
Fibrinolysis in Patients with Liver Disease
Patients with liver disease acquire complex changes in their hemostatic system. Historically, these patients were considered to have a bleeding tendency related, in part, to a hyperfibrinolytic state. However, studies using more modern fibrinolysis tests have questioned the presence of a hyperfibrinolytic state in patients with liver disease and its association with bleeding risk. It may be that the sickest patients with liver disease do have fibrinolytic abnormalities. However, the debate on the fibrinolytic state of patients with (decompensated) cirrhosis or critically ill liver disease is complicated by the fact that hypo- and hyperfibrinolysis have been poorly defined. This could, in part, be explained by the lack of reliable tests that assess a patient's fibrinolytic status. Moreover, large clinical studies on the relationship between bleeding and fibrinolysis in patients with liver disease are scarce. Here, we provide an overview of the current knowledge on fibrinolysis in various types of liver diseases and possible implications as a target for therapeutic strategies in liver disease. As antifibrinolytic therapy has been shown to be safe and effective during liver transplantation, it could potentially be of use in patients with (either laboratory-established or suspected) hyperfibrinolysis-related bleeding.</p
Netting Liver Disease:Neutrophil Extracellular Traps in the Initiation and Exacerbation of Liver Pathology
The liver plays a vital role in the immune system. Its unique position in the portal circulation and the architecture of the hepatic sinusoids, in combination with the wide-ranged population of immunocompetent cells, make the liver function as an immune filter. To aid in pathogen clearance, once challenged, the liver initiates the rapid recruitment of a wide variety of inflammatory cells, including neutrophils. These neutrophils, in conjunction with platelets, facilitate the release of neutrophil extracellular traps (NETs), which are web-like structures of decondensed nuclear DNA, histones, and neutrophil proteins. NETs function as both a physical and a chemical barrier, binding and killing pathogens circulating in the blood stream. In addition to their antimicrobial role, NETs also bind platelets, activate coagulation, and exacerbate host inflammatory response. This interplay between inflammation and coagulation drives microvascular occlusion, ischemia, and (sterile) damage in liver disease. Although direct clinical evidence of this interplay is scarce, preliminary studies indicate that NETs contribute to progression of liver disease and (thrombotic) complications. Here, we provide an overview of the pathological mechanisms of NETs in liver disease. In addition, we summarize clinical evidence for NETs in different disease etiologies and complications of liver disease and discuss the possible implications for the use of NETs as a diagnostic marker and a therapeutic target in liver disease
Persistent endotheliopathy in the pathogenesis of long COVID syndrome:Comment from von Meijenfeldt et al.
Post-transplant cholangiopathy:Classification, pathogenesis, and preventive strategies
Biliary complications are the most frequent cause of morbidity, re-transplantation, and even mortality after liver transplantation. In general, biliary leakage and anastomotic and non-anastomotic biliary strictures (NAS) can be recognized. There is no consensus on the exact definition of NAS and different names and criteria have been used in literature. We propose to use the term post-transplant cholangiopathy for the spectrum of abnormalities of large donor bile ducts, that includes NAS, but also intraductal casts and intrahepatic biloma formation, in the presence of a patent hepatic artery. Combinations of these manifestations of cholangiopathy are not infrequently found in the same liver and ischemia-reperfusion injury is generally considered the common underlying mechanism. Other factors that contribute to post-transplant cholangiopathy are biliary injury due to bile salt toxicity and immune-mediated injury. This review provides an overview of the various types of post-transplant cholangiopathy, the presumed pathogenesis, clinical implications, and preventive strategies
Prophylactic fresh frozen plasma and platelet transfusion have a prothrombotic effect in patients with liver disease
Background and Aims Patients with liver disease acquire complex changes in their hemostatic system, resulting in prolongation of the international normalized ratio and thrombocytopenia. Abnormalities in these tests are commonly corrected with fresh frozen plasma (FFP) or platelet transfusions before invasive procedures. Whether these prophylactic transfusions are beneficial and truly indicated is increasingly debated. In this study, we studied ex vivo effects of FFP and platelet transfusions in patients with liver disease-associated hemostatic changes in a real-life clinical setting. Methods We included 19 patients who were deemed to require prophylactic FFP transfusion by their treating physician and 13 that were prescribed platelet transfusion before a procedure. Hemostatic status was assessed in blood samples taken before and after transfusion and compared with healthy controls (n = 20). Results Ex vivo thrombin generation was preserved in patients with liver disease before FFP transfusion. Following FFP transfusion, both in and ex vivo thrombin generation significantly increased, as evidenced by a 92% and 38% increase in thrombin-antithrombin and prothrombin fragment 1 + 2 levels, respectively, and a 20% increase in endogenous thrombin potential. Platelet counts increased from 28 [21-41] x 10(9)/L before to 43 [39-64] x 10(9)/L after platelet transfusion (P <.01), and was accompanied by increases in in vivo markers of hemostatic activation. Conclusions FFP and platelet transfusion resulted in increased thrombin generation and platelet counts in patients with liver disease, indicating a prothrombotic effect. However, whether all transfusions were truly indicated and had a clinically relevant effect is questionable