Matches in SemOpenAlex for { <https://semopenalex.org/work/W2899856840> ?p ?o ?g. }
Showing items 1 to 86 of
86
with 100 items per page.
- W2899856840 endingPage "112" @default.
- W2899856840 startingPage "110" @default.
- W2899856840 abstract "Both basic and applied studies dealing with aspects of hemostasis in patients with liver diseases have spurred significant controversy over the last two decades 1.Lisman T. Porte R.J. Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases.Res Pract Thromb Haemost. 2017; 1: 150-61Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar. Clinically, we have learnt that patients with liver diseases do not necessarily have a hemostatic defect resulting in a bleeding tendency. Instead, these patients appear to be in hemostatic balance, owing to declines in both prohemostatic and antihemostatic pathways, and may experience both bleeding and thrombotic complications when this reset hemostatic balance is offset 2.Lisman T. Porte R.J. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences.Blood. 2010; 116: 878-85Crossref PubMed Scopus (431) Google Scholar. These insights into the hemostatic status of these patients have led to the realization that correction of hemostasis before interventional procedures is frequently not required, and can even do harm. Major procedures, notably liver transplantation, can be performed in patients with profound ‘coagulopathy’ (defined as thrombocytopenia and/or prolongations in the prothrombin time) without the requirement for any prohemostatic interventions 3.Massicotte L. Thibeault L. Roy A. Classical notions of coagulation revisited in relation with blood losses, transfusion rate for 700 consecutive liver transplantations.Semin Thromb Hemost. 2015; 41: 538-46Crossref PubMed Scopus (51) Google Scholar. Not all proceduralists, however, accept the change in dogma, and require correction of hemostasis prior to minor invasive procedures with an established low bleeding risk. Despite overwhelming clinical and laboratory evidence arguing against correction of the prothrombin time prior to invasive procedures in patients with chronic liver disease 4.Lisman T. Porte R.J. Value of preoperative hemostasis testing in patients with liver disease for perioperative hemostatic management.Anesthesiology. 2017; 126: 338-44Crossref PubMed Scopus (38) Google Scholar, some guidelines specifically state that correction should be performed 5.Patel I.J. Davidson J.C. Nikolic B. Salazar G.M. Schwartzberg M.S. Walker T.G. Saad W.A. Standards of Practice Committee, with Cardiovascular and Interventional Radiological Society of Europe (CIRSE) EndorsementConsensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image‐guided interventions.J Vasc Interv Radiol. 2012; 23: 727-36Abstract Full Text Full Text PDF PubMed Scopus (424) Google Scholar. In organized attempts to convince proceduralists and professional organizations, my colleagues and I have frequently heard ‘Are you telling me that everything I have been taught in medical school was wrong?’ Obviously, this is not the case, as tests such as the prothrombin time were never designed to predict (procedural) bleeding, but, unfortunately, they have been used as such. Acceptance of changes in dogma is sometimes slow. In this issue of the Journal of Thrombosis and Haemostasis, Poole et al. present data that made me wonder whether everything I have been taught in the 20 years in which I have studied thrombosis and hemostasis is wrong 6.Poole L.G. Pant A. Baker K.S. Kopec A.K. Cline‐Fedewa H.M. Lismaa S.E. Flick M.J. Luyendyk J.P. Chronic liver injury drives non‐traditional intrahepatic fibrin(ogen) cross‐linking via tissue transglutaminase.J Thromb Haemost. 2018; 17: 113-25Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar. In a mouse model of chronic liver injury, it was demonstrated that crosslinked fibrin(ogen) is deposited in a process that does not require fibrinogen‐to‐fibrin conversion or factor XIII. Rather, these ‘non‐traditional’ clots can be formed from fibrinogen that is crosslinked by tissue transglutaminase (TG2), which is a multifunctional and widely expressed protein that has been implicated in diabetes and celiac disease, and as a player in inflammation, apoptosis, and matrix remodeling 7.Odii B.O. Coussons P. Biological functionalities of transglutaminase 2 and the possibility of its compensation by other members of the transglutaminase family.ScientificWorldJournal. 2014; 2014: 714561Crossref PubMed Scopus (23) Google Scholar. Although TG2 is known to crosslink fibrin(ogen) in vitro 8.Murthy S.N. Lorand L. Cross‐linked A alpha.gamma chain hybrids serve as unique markers for fibrinogen polymerized by tissue transglutaminase.Proc Natl Acad Sci USA. 1990; 87: 9679-82Crossref PubMed Scopus (31) Google Scholar, this study is the first to document TG2‐dependent fibrin(ogen) crosslinking in vivo. Interestingly, intrahepatic deposition of non‐traditional fibrin(ogen) had no effect on the severity of disease in this model, and this challenges a second dogma in the field of hemostasis and liver diseases. This study provides the first evidence that the beneficial effects of anticoagulants in delaying the progression of liver disease in animals and humans probably result from inhibition of thrombin rather than inhibition of fibrin formation, and therefore argues against the theory of ‘parenchymal extinction’, i.e. microthrombosis caused by intrahepatic clot formation, as the driver of progression of chronic liver disease 9.Wanless I.R. Wong F. Blendis L.M. Greig P. Heathcote E.J. Levy G. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension.Hepatology. 1995; 21: 1238-47PubMed Google Scholar, 10.Anstee Q.M. Wright M. Goldin R. Thursz M.R. Parenchymal extinction: coagulation and hepatic fibrogenesis.Clin Liver Dis. 2009; 13: 117-26Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar. The two seminal findings from this study – crosslinked clots can be formed without thrombin‐mediated fibrinogen‐to‐fibrin conversion, without the requirement for activated FXIII (FXIIIa) activity, and intrahepatic fibrin(ogen) deposition does not alter the progression of chronic liver disease, give rise to a wide array of questions.1.Are these ‘non‐traditional’ fibrinogen clots also formed in humans? As TG2‐crosslinked fibrinogen has unique structural characteristics (i.e. specific α–γ hybrid crosslinks) 8.Murthy S.N. Lorand L. Cross‐linked A alpha.gamma chain hybrids serve as unique markers for fibrinogen polymerized by tissue transglutaminase.Proc Natl Acad Sci USA. 1990; 87: 9679-82Crossref PubMed Scopus (31) Google Scholar, examination of fibrin(ogen) structures in, for example, biopsies of human diseased liver, or in human vascular clots (see below), should be possible. In fact, it was already stated in an article published in 1991 that ‘Thus, whenever a tissue transglutaminase might escape from cells into the plasma environment where it could directly interact with fibrinogen … diagnostic analysis should include a search for this internally crosslinked monomeric form of fibrinogen’ 11.Murthy S.N. Wilson J. Guy S.L. Lorand L. Intramolecular crosslinking of monomeric fibrinogen by tissue transglutaminase.Proc Natl Acad Sci USA. 1991; 88: 10601-4Crossref PubMed Scopus (26) Google Scholar, but, to my knowledge, this proposal was never followed up.2.Are these clots truly ‘clots’ or are they, for example, thin ‘sheets’ of crosslinked fibrinogen that are attached to collagen, as suggested by the authors? The shape and localization of intrahepatic fibrin(ogen) have not been extensively explored, and more in‐depth (electron)microscopy studies are urgently needed to provide a better understanding of the nature of these fibrin(ogen) structures that have only been identified with immunohistochemical labeling of liver sections 12.Kopec A.K. Luyendyk J.P. Role of fibrin(ogen) in progression of liver disease: guilt by association?.Semin Thromb Hemost. 2016; 42: 397-407Crossref PubMed Scopus (14) Google Scholar.3.What initiates intrahepatic fibrinogen deposition? If intrahepatic activation of coagulation is not required as such, what signals are required for fibrinogen deposition and TG2‐mediated crosslinking? Deposition of collagen, which is the hallmark of hepatic fibrosis, could be the key driver.4.Is non‐traditional fibrin(ogen) deposition the hallmark of all types of liver injury? Fibrin(ogen) has been found in many experimental settings of chronic or acute liver injury. However, the mechanisms by which fibrin(ogen) is deposited may be different. For example, in acetaminophen‐induced acute liver injury, in which no deposition of collagen occurs, there is massive intrahepatic crosslinked fibrin deposition, which appears not to affect injury, but does facilitate repair 13.Kopec A.K. Joshi N. Cline‐Fedewa H. Wojcicki A.V. Ray J.L. Sullivan B.P. Froehlich J.E. Johnson B.F. Flick M.J. Luyendyk J.P. Fibrin(ogen) drives repair after acetaminophen‐induced liver injury via leukocyte alphaMbeta2 integrin‐dependent upregulation of Mmp12.J Hepatol. 2017; 66: 787-97Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar. In a model of cholestatic acute liver injury, however, fibrin(ogen) deposits occur and appear to accelerate injury 14.Luyendyk J.P. Mackman N. Sullivan B.P. Role of fibrinogen and protease‐activated receptors in acute xenobiotic‐induced cholestatic liver injury.Toxicol Sci. 2011; 119: 233-43Crossref PubMed Scopus (16) Google Scholar. Is this because the types of clot differ between these models? Also, in a model of fatty liver disease, crosslinked fibrin(ogen) deposits have been identified in the liver and adipose tissue 15.Kopec A.K. Abrahams S.R. Thornton S. Palumbo J.S. Mullins E.S. Divanovic S. Weiler H. Owens 3rd, A.P. Mackman N. Goss A. van Ryn J. Luyendyk J.P. Flick M.J. Thrombin promotes diet‐induced obesity through fibrin‐driven inflammation.J Clin Invest. 2017; 127: 3152-66Crossref PubMed Scopus (71) Google Scholar, and again it would be of interest to identify the make‐up of these deposits.5.Is parenchymal extinction, i.e. the progression of liver injury by intrahepatic microthrombi, not a relevant pathological mechanism at all, or does this depend on the nature, extent and phase of liver injury? The observation that fibrinogen knockout is protective against acute biliary injury induced by the hepatotoxicant α‐naphthylisothiocyanate suggests that parenchymal extinction may be relevant in some forms of liver injury 14.Luyendyk J.P. Mackman N. Sullivan B.P. Role of fibrinogen and protease‐activated receptors in acute xenobiotic‐induced cholestatic liver injury.Toxicol Sci. 2011; 119: 233-43Crossref PubMed Scopus (16) Google Scholar. A role of fibrin in many other models has been suggested, but evidence has always been circumstantial, and it has been suggested that fibrin(ogen) deposition primarily acts as an innocent bystander 12.Kopec A.K. Luyendyk J.P. Role of fibrin(ogen) in progression of liver disease: guilt by association?.Semin Thromb Hemost. 2016; 42: 397-407Crossref PubMed Scopus (14) Google Scholar. Perhaps a systematic screen of various clinically relevant liver injury models in the fibrinogen knockout or fibrinogen AEK mouse would be of interest.6.Are these non‐traditional clots formed elsewhere? If collagen is the initiator of non‐traditional fibrin(ogen) deposition, these clots may be formed in fibrotic lesions in other organs. Models of cardiac 16.Schnitt S.J. Stillman I.E. Owings D.V. Kishimoto C. Dvorak H.F. Abelmann W.H. Myocardial fibrin deposition in experimental viral myocarditis that progresses to dilated cardiomyopathy.Circ Res. 1993; 72: 914-20Crossref PubMed Scopus (32) Google Scholar, pulmonary 17.Shea B.S. Probst C.K. Brazee P.L. Rotile N.J. Blasi F. Weinreb P.H. Black K.E. Sosnovik D.E. Van Cott E.M. Violette S.M. Caravan P. Tager A.M. Uncoupling of the profibrotic and hemostatic effects of thrombin in lung fibrosis.JCI Insight. 2017; 2: e86608Crossref PubMed Scopus (53) Google Scholar and renal fibrosis 18.Craciun F.L. Ajay A.K. Hoffmann D. Saikumar J. Fabian S.L. Bijol V. Humphreys B.D. Vaidya V.S. Pharmacological and genetic depletion of fibrinogen protects from kidney fibrosis.Am J Physiol Renal Physiol. 2014; 307: F471-84Crossref PubMed Scopus (31) Google Scholar, for example, are known to be accompanied by fibrin(ogen) deposition, and it would be of interest to assess the requirement for fibrinogen cleavage by thrombin, and crosslinking by FXIIIa, in these models. Could non‐traditional clots be formed intravascularly? Portal vein thrombosis is a poorly understood, but common, complication of chronic liver disease that is frequently resistant to anticoagulant therapy 19.Loffredo L. Pastori D. Farcomeni A. Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: a systematic review and meta‐analysis.Gastroenterology. 2017; 153: 480-7Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar. It is tempting to speculate that (some) portal vein thrombi are non‐traditional clots, which will be, by definition, unresponsive to anticoagulants. Although TG2 is thought to be absent from plasma under normal conditions, it is present in red blood cells, and TG2 could contribute to fibrin(ogen) crosslinking in localized or systemic thrombotic diseases. A contribution of TG2 to clot crosslinking, particularly under hemolytic conditions, was suggested in the late 1980s 20.Lorand L. Dailey J.E. Turner P.M. Fibronectin as a carrier for the transglutaminase from human erythrocytes.Proc Natl Acad Sci USA. 1988; 85: 1057-9Crossref PubMed Scopus (59) Google Scholar, but this concept has never been extensively validated. Thrombotic conditions accompanied by hemolysis, including sickle cell disease, disseminated intravascular coagulation, thrombotic microangiopathies such as thrombotic thrombocytopenic purpura, hemolytic–uremic syndrome, and HELLP syndrome, are all difficult‐to‐treat conditions characterized by deposition of fibrin within organs. It is not inconceivable that some of these fibrin clots are, in fact, the non‐traditional fibrinogen deposits identified by Poole et al. Thus, it is of interest to establish whether these ‘non‐traditional’ clots are specific for liver diseases or clinical conditions in which intrahepatic fibrin deposition occurs, or whether they represent a more widespread phenomenon, perhaps even contributing to intravascular thrombosis. Next, it will be of interest to ascertain whether there are situations in which these non‐traditional clots do harm. In the current study, the non‐traditional clots appeared to be true innocent bystanders, as progression of liver injury was identical between wild‐type and TG2 knockout mice. However, the authors’ conclusion that ‘these studies provide strong experimental evidence that the mechanism connecting coagulation activity to liver fibrosis occurs via a pathway independent of hepatic fibrin(ogen) deposition in the chronically damaged liver’ may be premature, as the role of these clots may be context‐dependent 12.Kopec A.K. Luyendyk J.P. Role of fibrin(ogen) in progression of liver disease: guilt by association?.Semin Thromb Hemost. 2016; 42: 397-407Crossref PubMed Scopus (14) Google Scholar. Also, it is possible that intrahepatic clots do not drive progression of disease, but do affect complications of chronic liver disease, notably portal hypertension. A recent study demonstrated relief of portal hypertension by rivaroxaban in carbon tetrachloride‐treated rats 21.Vilaseca M. Garcia‐Caldero H. Lafoz E. Garcia‐Irigoyen O. Avila M.A. Reverter J.C. Bosch J. Hernandez‐Gea V. Gracia‐Sancho J. Garcia‐Pagan J.C. The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells.Hepatology. 2017; 65: 2031-44Crossref PubMed Scopus (51) Google Scholar. This effect was proposed to be multifactorial, with reduced intrahepatic microthrombosis as one of the contributing mechanisms. Even if intrahepatic thrombosis proves not to significantly contribute to the progression of liver diseases, exploration of a functional role of non‐traditional fibrinogen clots in other settings, notably intravascular thrombosis, remains of interest. Should there be situations in which TG2‐crosslinked fibrinogen has a functional role, an interesting question will be whether TG2 is a viable target for pharmacological interventions. TG2 has multiple functions, not only as a transglutaminase, but also as a G‐protein for several seven transmembrane receptors and as a coreceptor for β1 and β3 integrins, and has been implicated in a wide variety of diseases 7.Odii B.O. Coussons P. Biological functionalities of transglutaminase 2 and the possibility of its compensation by other members of the transglutaminase family.ScientificWorldJournal. 2014; 2014: 714561Crossref PubMed Scopus (23) Google Scholar. Nevertheless, small‐molecule inhibitors of TG2 have been developed, and one of these is undergoing early clinical studies, specifically for patients with celiac disease (EudraCT Number: 2017‐002241‐30). Whether the inhibition of alternative functions of TG2 disqualifies TG2 inhibitors as agents to prevent intravascular or extravascular ‘non‐traditional’ fibrin(ogen) deposition would be an important area of investigation. In summary, the study by Poole et al. has provided solid evidence against a role of intrahepatic fibrin deposition in the progression of disease, at least in the chronic carbon tetrachloride model. During the study of the role of fibrin deposition in driving liver injury, the authors have detailed a thrombin‐independent and FXIII‐independent way in which fibrinogen can be deposited and crosslinked, at least within the liver. Whether this observation has wider implications remains to be investigated, but it is certainly an attractive hypothesis. The author states that he has no conflict of interest." @default.
- W2899856840 created "2018-11-16" @default.
- W2899856840 creator A5074302578 @default.
- W2899856840 date "2019-01-01" @default.
- W2899856840 modified "2023-09-30" @default.
- W2899856840 title "Crosslinked clots formed independently of factor XIII and without fibrinogen‐to‐fibrin conversion – is this a liver‐specific phenomenon?" @default.
- W2899856840 cites W1574141134 @default.
- W2899856840 cites W1968641413 @default.
- W2899856840 cites W2017405539 @default.
- W2899856840 cites W2038040804 @default.
- W2899856840 cites W2042894685 @default.
- W2899856840 cites W2054282727 @default.
- W2899856840 cites W2090387429 @default.
- W2899856840 cites W2105369234 @default.
- W2899856840 cites W2118603950 @default.
- W2899856840 cites W2138966030 @default.
- W2899856840 cites W2157647405 @default.
- W2899856840 cites W2165301593 @default.
- W2899856840 cites W2346659241 @default.
- W2899856840 cites W2399199659 @default.
- W2899856840 cites W2559416201 @default.
- W2899856840 cites W2560453688 @default.
- W2899856840 cites W2583115659 @default.
- W2899856840 cites W2610258648 @default.
- W2899856840 cites W2611240878 @default.
- W2899856840 cites W2739353751 @default.
- W2899856840 cites W2742683725 @default.
- W2899856840 cites W2899856840 @default.
- W2899856840 cites W2900355193 @default.
- W2899856840 doi "https://doi.org/10.1111/jth.14328" @default.
- W2899856840 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7379741" @default.
- W2899856840 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30412653" @default.
- W2899856840 hasPublicationYear "2019" @default.
- W2899856840 type Work @default.
- W2899856840 sameAs 2899856840 @default.
- W2899856840 citedByCount "1" @default.
- W2899856840 countsByYear W28998568402019 @default.
- W2899856840 crossrefType "journal-article" @default.
- W2899856840 hasAuthorship W2899856840A5074302578 @default.
- W2899856840 hasBestOaLocation W28998568401 @default.
- W2899856840 hasConcept C111472728 @default.
- W2899856840 hasConcept C126322002 @default.
- W2899856840 hasConcept C138885662 @default.
- W2899856840 hasConcept C185592680 @default.
- W2899856840 hasConcept C203014093 @default.
- W2899856840 hasConcept C2779036427 @default.
- W2899856840 hasConcept C2779672106 @default.
- W2899856840 hasConcept C50335755 @default.
- W2899856840 hasConcept C54173615 @default.
- W2899856840 hasConcept C71924100 @default.
- W2899856840 hasConceptScore W2899856840C111472728 @default.
- W2899856840 hasConceptScore W2899856840C126322002 @default.
- W2899856840 hasConceptScore W2899856840C138885662 @default.
- W2899856840 hasConceptScore W2899856840C185592680 @default.
- W2899856840 hasConceptScore W2899856840C203014093 @default.
- W2899856840 hasConceptScore W2899856840C2779036427 @default.
- W2899856840 hasConceptScore W2899856840C2779672106 @default.
- W2899856840 hasConceptScore W2899856840C50335755 @default.
- W2899856840 hasConceptScore W2899856840C54173615 @default.
- W2899856840 hasConceptScore W2899856840C71924100 @default.
- W2899856840 hasIssue "1" @default.
- W2899856840 hasLocation W28998568401 @default.
- W2899856840 hasLocation W28998568402 @default.
- W2899856840 hasLocation W28998568403 @default.
- W2899856840 hasLocation W28998568404 @default.
- W2899856840 hasLocation W28998568405 @default.
- W2899856840 hasLocation W28998568406 @default.
- W2899856840 hasOpenAccess W2899856840 @default.
- W2899856840 hasPrimaryLocation W28998568401 @default.
- W2899856840 hasRelatedWork W1146534089 @default.
- W2899856840 hasRelatedWork W126825949 @default.
- W2899856840 hasRelatedWork W2007707310 @default.
- W2899856840 hasRelatedWork W2012171708 @default.
- W2899856840 hasRelatedWork W2021918441 @default.
- W2899856840 hasRelatedWork W2039457448 @default.
- W2899856840 hasRelatedWork W2049170872 @default.
- W2899856840 hasRelatedWork W2103509293 @default.
- W2899856840 hasRelatedWork W2115151630 @default.
- W2899856840 hasRelatedWork W2554645977 @default.
- W2899856840 hasVolume "17" @default.
- W2899856840 isParatext "false" @default.
- W2899856840 isRetracted "false" @default.
- W2899856840 magId "2899856840" @default.
- W2899856840 workType "article" @default.