Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases

Patients with liver diseases may develop alterations in all components of the hemostatic system. Thrombocytopenia, low levels of coagulation factors and inhibitors, low levels of fibrinolytic proteins, and increased levels of endothelial-derived proteins such as von Willebrand factor are all part of the coagulopathy of liver disease. Due to concomitant changes in pro- and antihemostatic drivers, the net effects of these complex hemostatic changes have long been unclear. According to current concepts, the hemostatic system of patients with liver disease is in an unstable balance, which explains the occurrence of both bleeding and thrombotic complications. This review will discuss etiology and management of bleeding and thrombosis in liver disease and will outline unsolved clinical questions. In addition, we will discuss the role of intrahepatic activation of coagulation for progression of liver disease, a novel paradigm with potential consequences for the general management of patients with liver disease.</p

Laparoscopic Versus Open Cholecystectomy: A Prospective Matched-Cohort Study

To compare the results of laparoscopic cholecystectomy (LC) and open cholecystectomy (OC) for symptomatic cholelithiasis in elective surgery we performed a prospective matched-cohort study. Hundred consecutive patients who underwent LC in the period Sept. 1990-June 1992, and 100 patients who were age and sex matched and underwent an elective OC in the foregoing two years (1989-1990) were studied. The median operation time for LC (75, 40-180 min) was significantly longer than for OC (55, 20-155 min; p < 0.001). Postoperative hospitalization was significantly shorter after LC (3, 1-16 days), compared with OC (7, 4-22 days; p<0.001). Conversion of LC to OC occurred in 12 (12%) patients initially scheduled to undergo LC. Complications occurred in 5 patients (5%) after LC and in 5 patients (5%) after OC. The calculated expenses (operation and postoperative hospitalization, 3rd class) were approximately fl. 3740,- for LC (excl. investments for pieces of apparatus) and fl. 6725,- for OC. This study demonstrates that LC can be performed safely with the number of complications comparable to those for OC. Bile duct injury is a serious potential threat. The main advantages ofLC are the minimal trauma, with more rapid recovery. Insurers seem to benefit from reduced postoperative disability and earlier discharge

Blood Markers of Portal Hypertension Are Associated with Blood Loss and Transfusion Requirements during Orthotopic Liver Transplantation

There is increasing evidence that portal hypertension plays a major role in bleeding risk during orthotopic liver transplantation (OLT). We investigated the association between preoperative blood levels of von Willebrand factor (VWF) and soluble CD163 (sCD163), which are established markers of portal hypertension, and blood loss and transfusion requirements during OLT. We measured levels of VWF and sCD163 in preoperative serum samples of 168 adult patients undergoing a primary OLT between 1998 and 2012. Preoperative levels of VWF and sCD163 correlated with the model of end-stage liver disease (MELD) score (r = 0.414, p < 0.001 and r = 0.382, p < 0.001, respectively). Patients with high VWF or sCD163 levels (VWF and sCD163 levels above the median) had a substantially increased risk of needing red blood cell transfusion compared with patients with low VWF or sCD163 levels (VWF and sCD163 levels below the median) (odds ratio 3.5 [95% confidence interval, CI 1.7-7.0] and 2.3 [95% CI 1.1-4.5], respectively). Blood loss was highest in patients with both high VWF or sCD163 levels and a high preoperative international normalized ratio. Elevated blood levels of markers of portal hypertension are associated with increased blood loss and transfusion requirements during OLT and support the notion that portal hypertension is an important contributor to perioperative blood loss

Anticoagulant Management and Synthesis of Hemostatic Proteins during Machine Preservation of Livers for Transplantation

Liver transplantation remains the only curative treatment for patients with end-stage liver disease. Despite a steadily increasing demand for suitable donor livers, the current pool of donor organs fails to meet this demand. To resolve this discrepancy, livers traditionally considered to be of suboptimal quality and function are increasingly utilized. These marginal livers, however, are less tolerant to the current standard cold preservation of donor organs. Therefore, alternative preservation methods have been sought and are progressively applied into clinical practice. Ex situ machine perfusion is a promising alternative preservation modality particularly for suboptimal donor livers as it provides the ability to resuscitate, recondition, and test the viability of an organ prior to transplantation. This review addresses the modalities of machine perfusion currently being applied, and particularly focuses on the hemostatic management employed during machine perfusion. We discuss the anticoagulant agents used, the variation in dosage, and administration, as well as the implications of perfusion for extended periods of time in terms of coagulation activation associated with production of coagulation factors during perfusion. Furthermore, in regard to viability testing of an organ prior to transplantation, we discuss the possibilities and limitations of utilizing the synthesis of liver-derived coagulation factors as potential viability markers

Normothermic liver machine perfusion as a dynamic platform for regenerative purposes. What does the future have in store for us?

Liver transplantation has become an immense success; nevertheless, far more recipients are registered on waiting lists than there are available donor livers for transplantation. High-risk, extended criteria donor livers are increasingly used to reduce the discrepancy between organ demand and supply. Especially for high-risk livers, dynamic preservation using machine perfusion can decrease post-transplantation complications and may increase donor liver utilization by resuscitation and viability testing before transplantation. To further increase the availability of donor livers suitable for transplantation, new strategies are required that make it possible to use organs that are initially too damaged to be transplanted. With the current progress in experimental liver transplantation research, (long-term) normothermic machine perfusion may be used in the future as a dynamic platform for regenerative medicine approaches, enabling repair and regeneration of injured donor livers. Currently explored therapeutics such as defatting cocktails, ribonucleic acid interference, senolytics, and stem cell therapy may assist in the repair and/or regeneration of injured livers before transplantation. This review will provide a forecast of the future utility of normothermic machine perfusion for repair and regeneration of damaged donor livers to ultimately decrease the imbalance between donor liver demand and supply

Graft repair during machine perfusion:a current overview of strategies

The possibility to repair injured donor livers during ex situ machine perfusion might increase the utilization of ECD-livers. Application of defatting agents is currently explored in clinical trials, whereas other therapeutics require further research or optimization before entering clinical research.</p

Vitamin E Attenuates the Progression of Non-Alcoholic Fatty Liver Disease Caused by Partial Hepatectomy in Mice

The progression of non-alcoholic fatty liver disease (NAFLD) likely involves a 'multiple hit' mechanism. We hypothesized that partial hepatectomy, a procedure performed frequently in patients with NAFLD, would accelerate the progression of disease.C57BL/6JolaHsd mice were fed a choline-deficient L-amino acid-defined diet (CD-AA) or a choline-sufficient L-amino acid-defined control diet (CS-AA). Part of the mice in the CD-AA group received a diet enriched in vitamin E (~20 mg /day). Two weeks after the start of the diet, mice underwent a partial hepatectomy or a sham operation.In the CD-AA group, NAFLD activity scores were significantly higher at 7 days after partial hepatectomy compared to the sham operated mice (3.7 ± 1.3 vs. 1.8 ± 0.7; P<0.05). In addition, TBARS, a measure for oxidative stress, in liver tissue of the CD-AA group were significantly higher at day 1, 3 and 7 after partial hepatectomy compared to the sham operated mice (P<0.05). Vitamin E therapy significantly reduced TBARS level at day 7 after partial hepatectomy compared to the CD-AA diet group (P< 0.05). Vitamin E suppletion reduced NAFLD activity score at day 7 after partial hepatectomy compared to the CD-AA group (2.3 ± 0.8 vs. 3.8 ± 1.0; P<0.05).Partial hepatectomy accelerates the progression of NAFLD. Disease progression induced by partial hepatectomy is substantially attenuated by vitamin E

Topical haemostatic agents in liver surgery: do we need them?

AbstractBackgroundWorldwide, partial liver resections are increasingly being performed for primary or secondary hepatic malignancies. There are various techniques to reduce blood loss druing liver surgery. Several topical haemostatic agents have been developed to improve haemostasis of the resection surface and these agents are used more and more, even although the true effects remain unclear.MethodsThe present literature about the use of topical haemostatic agents in liver surgery was reviewed. Furthermore we conducted a Dutch national survey to explore the use of and belief in these agents in liver surgery.ResultsThe Dutch national survey among surgeons showed that topical haemostatic agents are frequently used not only to lower intra-operative blood loss or shorten time to haemostasis, but even more importantly, to reduce resection surface related complications such as bile leakage, postoperative haemorrhage and abscess formation. Although various topical haemostatic agents have been shown to reduce intra-operative time to haemostasis at the resection surface after liver resections, there is no scientific proof that these topical haemostatic agents really reduce resection surface related complications.ConclusionThis review highlights the need for more randomized clinical trials to investigate the efficacy of topical haemostatic agents in reducing resection surface related complications

Outflow obstruction after living donor liver transplantation managed with a temporary vena cava filter:A case report

Introduction: Outflow obstruction is a rare but critical vascular complication in liver transplantation, which may lead to graft loss and mortality. We report a case of caval vein outflow obstruction due to retrohepatic compression after living donor liver transplantation (LDLT), which was managed by temporary implantation of a vena cava filter. Presentation of case: A 63-year-old male with end stage liver disease presented with caval vein outflow obstruction and massive ascites 12 days after right lobe LDLT. We opted for a minimally invasive approach and implanted a vena cava filter at the compressed site through transjugular route. The patient's ascites drainage significantly decreased and graft function maintained stable after the intervention. On day 50 posttransplant, the filter was successfully removed and the patient was discharged without complications. Discussion: Outflow obstruction after liver transplantation can result from anastomotic stenosis, graft size mismatch, thrombosis or compression of the outflow tract. Various management strategies have been employed both peri- and posttransplant, ranging from surgical interventions to minimally-invasive techniques. The treatment strategy should be tailored to the individual case, considering the timing of presentation and the specific cause for the obstruction. Conclusion: We successfully managed a case of compressive outflow obstruction by temporary implantation of a vena cava filter after LDLT. The vena cava filter was safely removed under angiography.</p