2,650 research outputs found
The international normalized ratio - Great for prediction of bleeding in patients taking vitamin K antagonists, useless for prediction of bleeding in patients with chronic liver disease
Full text linkComment to " Antithrombin III Administration for Portal Vein Thrombosis in Patients with Liver Disease: A Randomized Double-Blind Controlled Trial"
Full text linkLevels of angiogenic proteins in plasma and platelets are not different between patients with hepatitis B/C-related cirrhosis and patients with cirrhosis and hepatocellular carcinoma
No full textIncreasing evidence suggests that levels of angiogenic proteins within blood platelets change at the earliest stages of cancer development and may thus provide a promising diagnostic and prognostic tool. Patients with cirrhosis have increased risk of developing hepatocellular carcinoma (HCC). We aimed to study whether development of HCC in hepatitis-related cirrhosis results in changes in platelet levels of angiogenic proteins. We studied the intraplatelet levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), endostatin, platelet factor 4 (PF4) and thrombospondin type 1 (TSP-1) in 38 consecutive patients with hepatitis B-or C-related liver cirrhosis with or without HCC in addition to plasma levels of the same proteins. Twenty healthy volunteers were included to establish reference values for the various tests. Intraplatelet levels of VEGF, bFGF, HGF and endostatin were significantly higher in patients compared to controls. Intraplatelet levels of PDGF, PF4 and TSP-1 were comparable between patients and controls. Plasma levels of VEGF, bFGF and endostatin were comparable between patients and controls. Plasma levels of PDGF, PF4 and TSP-1 were decreased in patients, but this difference disappeared when levels were corrected for platelet count. Intraplatelet and plasma levels of all proteins assessed were comparable between patients with and without HCC. In conclusion, the intraplatelet levels of some angiogenic proteins are elevated in cirrhosis, but do not discriminate between patients with and without HCC. Thus, intraplatelet levels of angiogenic proteins do not seem useful as diagnostic or prognostic biomarker of HCC in cirrhotic patients
No evidence for increased platelet activation in patients with hepatitis B- or C-related cirrhosis and hepatocellular carcinoma
No full textIntroduction: Cancer is a major risk factor for developing venous thromboembolism (VTE). Plasma hypercoagulability is an established risk factor for cancer-related VTE. In addition, thrombocytosis and hyperreactive platelets have been implicated in VTE and cancer progression. Cirrhosis is associated with changes in platelet number and function. The platelet activation status of patients with cirrhosis and hepatocellular carcinoma has not yet been established. Here we assessed the platelet activation status in patients with hepatitis-related cirrhosis in presence or absence of HCC. Materials and methods: We performed a cross-sectional study including thirty-eight consecutive patients with hepatitis B- or C-related liver cirrhosis in presence or absence of HCC. We studied basal and agonist-induced platelet activation using flow cytometry. In addition, we studied the plasma levels of von Willebrand factor (VWF) and the VWF-cleaving protease ADAMTS13. Twenty healthy volunteers served as controls. Results: We found no evidence of basal platelet activation in patients with cirrhosis compared to controls. However, we found reduced agonist-induced platelet activation in patients. No differences in the basal and agonist-induced platelets activation status between patients with or without HCC were detected. Plasma levels of VWF were increased and the levels of ADAMTS13 activity were decreased in patients compared to controls. No differences between the levels of VWF and ADAMTS13 in patients with or without HCC were detected. Conclusions: HCC development or recurrence in patients with hepatitis B- C-related cirrhosis does not appear to be associated with platelet activation and changes in pivotal proteins in primary hemostasis. (C) 2014 Elsevier Ltd. All rights reserved
Molecular mechanisms of platelet-mediated liver regeneration after partial hepatectomy
Full text linkDe lever heeft een enorm regeneratief vermogen nadat een deel van de lever verwijderd is of nadat schade door toxines is ontstaan. Rond 70% van de lever van een mens kan veilig verwijderd worden door middel van een partiële leverresectie. Dit zou noodzakelijk kunnen zijn bij patiënten met levercancer. Terwijl de lever in sommige gevallen dankzij het regeneratief vermogen kan herstellen, zijn er patiënten die uiteindelijk aan leverinsufficiëntie overleiden omdat de therapeutische opties erg gelimiteerd zijn. Daarom is er belangstelling om nieuwe therapeutische opties voor patiënten met leverinsufficiëntie te ontwikkelen. Bloedplaatjes staan bekend voor hun hemostatische functies toch is er recent ontdekt dat bloedplaatjes ook betrokken zijn bij de stimulatie van leverregeneratie. De molekulaire mechanismes achter bloedplaatjes gemedieerde leverregeneratie zijn grotendeels nog onduidelijk. In dit proefschrift worden de resultaten van verschillende in vitro en in vivo studies beschreven waarbij de onderliggende molekulaire mechanisms van bloedplaatjes gemedieerde leverregeneratie onderzocht worden. Op dit moment wordt er aangenomen dat groeifactoren, die in bloedplatjes opgeslaan zijn leverregeneratie bevorderen. In tegenstelling, hebben wij in een prospectieve klinische studie aangetoond dat er geen bewijs te vinden is dat deze groeifactoren daadwerkelijk betrokken zijn bij leverregeneratie. In een in vitro studie hebben wij een nieuwe mechansime opgehelderd, waarbij bloedplaatjes de groei van levercellen stimuleren. Wij hebben ontdekt dat bloedplaatjes (die geen celkern hebben en dus ook geen DNA) hun RNA kunnen overdragen aan de levercellen, die hiervan weer eiwitten kan maken. Dit proces is essentieel voor de stimulatie van levercellen door bloedplaatjes. Verder hebben wij in vivo modellen bloedplaatjes interactie met de regenererende lever bestudeerd. Deze studies hebben een “sleutel molecuul” te voorschijn gebracht dat cruciaal is voor de bloedplaatjes influx in de resterende lever en de leverregenertie. De studies die in dit proefschrift beschreven worden hebben voor beter inzicht in de molekulaire mechanismes betrokken bij bloedplaatjes gemedieerde leverregeneratie gezoorgd en potentiële nieuwe therapeutisch opties te voorschijn gebracht
Transplantation of high risk donor livers:Machine perfusion studies to improve and predict post transplant hepatobiliary function
Full text linkThere currently is a shortage of suitable donor livers in the Netherlands. In 2016, waiting list mortality was 17%. In that same year 32% of all donor livers were declined for transplantation, due to an estimated high risk of complications, such as primary non-function, early allograft dysfunction en biliary complications. In this dissertation was investigated if initially declined donor lives could potentially be used for transplantation. A combined protocol of hypo- and normothermic oxygenated machine perfusion was used to resuscitate and evaluate these initially declined donor livers (DHOPE-COR-NMP trial). During normothermic (body temperature) machine perfusion the liver had to meet certain criteria to be accepted for transplantation. These criteria reflected hepatobiliary function- and injury. The perfusion solution was based on artificial haemoglobin. The use of this HBOC-201- based perfusion solution was found to be safe. Furthermore, 20% extra livers were transplanted in the UMCG in 2018 with the DHOPE-COR-NMP protocol. In another study in this dissertation pH, bicarbonate and glucose in bile were shown to be accurate predictors of histological bile duct injury. Histological bile duct injury has been associated with biliary complications post transplantation. In the final chapter of the dissertation was investigated whether dual hypothermic oxygenated machine perfusion via the portal vein and hepatic artery (DHOPE) is superior to hypothermic oxygenated machine perfusion via the portal vein alone (HOPE). Porcine livers that underwent DHOPE had less hepatobiliary injury than porcine livers that underwent HOPE
Studies on bile duct Injury and the protective role of oxygenated machine perfusion in liver transplantation
Full text linkGalwegcomplicaties, in het bijzonder non-anastomotische galwegstricturen (NAS), zijn een veel voorkomend en moeilijk behandelbaar probleem na levertransplantatie. Kenmerkend voor deze complicatie is het ontstaan van vernauwingen van de galwegen in of net buiten de lever, waarbij patiënten zich vaak presenteren met symptomen van galwegobstructie. De doelstelling van dit proefschrift is om de oorzaken van galwegschade en de onderliggende etiologie van NAS beter te begrijpen. Daarnaast hebben we de rol van geoxygeneerde machineperfusie onderzocht in het verbeteren van orgaankwaliteit voor transplantatie en het potentieel voorkomen van complicaties na transplantatie, inclusief NAS. Concluderend, in dit proefschrift werd de onderliggende pathofysiologie van galwegschade tijdens levertransplantatie bestudeerd, de rol van geoxygeneerde machine perfusie in het verbeteren van orgaankwaliteit voor transplantatie en het voorkomen van galwegschade na transplantatie. Hopelijk leiden de veelbelovende resultaten van dit proefschrift tot een toenemend gebruik van de machineperfusie techniek om de orgaanselectie voor transplantatie te verbeteren
Re: Bleeding Risk and Management in Interventional Procedures in Chronic Liver Disease
Full text linkPlatelet-neutrophil interactions as drivers of inflammatory and thrombotic disease
Full text linkNeutrophils are well known for their role in infection and inflammatory disease and are first responders at sites of infection or injury. Platelets have an established role in hemostasis and thrombosis and are first responders at sites of vascular damage. However, neutrophils are increasingly recognized for their role in thrombosis, while the immunemodulatory properties of platelets are being increasingly studied. Platelets and neutrophils interact during infection, inflammation and thrombosis and modulate each other's functions. This review will discuss the consequences of platelet-neutrophil interactions in infection, thrombosis, atherosclerosis and tissue injury and repair
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