In this review, we analyze the epidemiology of thromboses related to end-stage liver disease (ESLD), discuss causes of hypercoagulability, describe susceptible populations, and critically evaluate proposed prophylaxis and treatment of thromboses. Classically, ESLD has been regarded as a model for coagulopathy, and patients were deemed to be at high risk for bleeding complications. Patients with ESLD are not auto-anticoagulated, and they do not have a lower risk of portal vein thrombosis, intracardiac thrombus formation, pulmonary embolism or hepatic artery thrombosis. Though the cause of hypercoagulability is multifactorial, endothelial dysfunction likely plays a central role for all patients with ESLD. Some subpopulations, such as patients with nonalcoholic steatohepatitis and autoimmune conditions, are at increased risk of thrombotic events as are patients of Hispanic ethnicity. The science behind prophylaxis of different types of clotting and treatment of thromboses is developing rapidly. A number of medications, including low molecular weight heparin, unfractionated heparin, aspirin, vitamin K antagonists, and direct oral anticoagulants can be used, but clear guidelines are lacking. Acute intraoperative clotting can be associated with high mortality. Routine use of transesophageal echocardiography can be helpful in early recognition and treatment of intraoperative thrombosis. Heparin should be reserved for cases of intracardiac thrombus/pulmonary embolism without hemodynamic instability. In unstable patients, low dose of recombinant tissue plasminogen activator can be used. In this new era of heightened awareness of thrombotic events in ESLD patients, prospective randomized trials are urgently needed to best guide clinical practice.
Intraoperative thromboembolism is a well-documented complication associated with orthotopic liver transplantation (OLT) but its identification and intraoperative treatment are still an emerging topic in anesthesia. Intracardiac thrombus during OLT is associated with a high mortality rate. There are only a few reports describing the successful management of thromboembolism during OLT. We describe a case where routine intraoperative transesophageal echocardiography during a live donor liver transplantation enabled early detection of an intracardiac thrombus with subsequent successful heparin treatment. Our case suggests that if an intracardiac thrombus is identified early (before hemodynamic instability occurs), the use of IV heparin may be a safe therapeutic option.
Background: Osteoarthritis is a mechanical abnormality characterized by chronic joint pain associated with degeneration of the articular cartilage, synovitis, and local inflammation, leading to loss of function and pain. A connection exists between the peripheral nervous system and inflammatory joint degeneration. The process by which inflammation is influenced by the nervous system is known as neuroinflammation. One of the neuropeptides involved in peripheral neuroinflammation is nociceptin, a peptide related to the opioid class of substances. Nociceptin has both pro-and anti-inflammatory effects. Some studies show that nociceptin can be measured in synovial fluid, while other studies have not been able to detect it. The presence of nociceptin in synovial fluid could imply a molecular role for the neuropeptide in the joint, both physiologically as well as pathophysiologically. The goal of this pilot study was to determine whether nociceptin was present in the synovial fluid of osteoarthritic knees. Methods: Patients undergoing primary total knee arthroplasty were enrolled after Institutional Review Board approval was obtained. Synovial fluid was aspirated from patients' operative knee joints and blood samples were obtained. A commercially available enzyme Immunoassay kit was used to test for nociceptin. A linear mixed-effects model was developed to account for the repeated measurements and baseline covariates. Least squares (adjusted) means were derived from the model to compare the sample types and to compare subgroups. Results: Twenty patients were included in this study. Nociceptin was detected in the synovial fluid and plasma of all patients. The mean concentration (± standard deviation) of nociceptin in synovial fluid was 28.7 ± 18.2 pg/ml. The mean concentration of nociceptin in plasma was 45.2 ± 24.3 pg/ml pre-procedure, and 40.1 ± 20.6 pg/ml posttourniquet deflation. The nociceptin concentration in synovial fluid was significantly lower than the nociceptin concentration in plasma, both pre-procedure and post-tourniquet deflation (p = 0.002 and p = 0.016 respectively). The nociceptin concentration in both plasma and synovial fluid was significantly lower in females versus males (p = 0.012). Conclusion: We demonstrated that nociceptin is present in synovial fluid and plasma of patients undergoing total knee arthroplasty. This implies a potential role for nociceptin in modulating inflammation in osteoarthritis.
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