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Title: The clinical utility of viscoelastic tests of coagulation (TEG® & ROTEM®) in liver disease and liver surgery
Author: Mallett, Susan Veronica
ISNI:       0000 0004 7428 9679
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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This thesis focuses on what is currently known about the haemostatic changes that occur in liver disease, and also those that follow major liver resection. Although there has been considerable work on the changes in coagulation in both acute and chronic liver disease in recent years, there has been far less attention to hepatic resection. This is also an important area for study as an elevation of PT/INR is common in the first few days after resection, yet these patients are known to have a high incidence of thromboembolic complications in the early post operative period, and this risk appears to increase with the extent of liver parenchyma resected. It is the central hypothesis of this thesis that global viscoelastic tests (TEG/ROTEM) by facilitating assessment of all the cellular components of the coagulation process in an integrated manner, and their summative effect on ultimate clot formation, strength and stability, provide more clinically relevant information than do conventional coagulation tests which only assess single end points of coagulation in plasma rather than in whole blood. Chapter one focuses on models of coagulation (traditional cascade model and the newer cell based model of haemostasis) and the limitations of traditional coagulation tests in liver disease. Chapter two discusses the principles of viscoelastic tests, their limitations and also their correlation with conventional coagulation tests. It also highlights that these tests can detect 'hypercoagulability' which may relate to an increased thrombotic risk, and also fibrinolysis, neither of which is readily detected using conventional tests of coagulation. Chapter three is a review and critical appraisal of the available literature on the utility of viscoelastic tests of coagulation in patients with both acute and chronic liver disease. The majority of patients with liver disease have 'normal' coagulation as assessed by these tests, and this may be seen as supporting the hypothesis of 're-balanced' haemostasis. Aspects such as hypercoagulability and the relation to thrombotic risk, and endogenous heparinoids as markers of infection and endothelial injury are highlighted. Chapter four is a review and critical appraisal of the available literature on the utility of viscoelastic tests of coagulation in patients undergoing liver transplantation. The literature is reviewed to determine their efficacy in predicting bleeding risk, and also to guide haemostatic therapy in the presence of active bleeding. Chapter five is a retrospective study to assess the prevalence of fibrinolysis in patients undergoing liver transplantation, and how this relates to subsequent need for blood transfusion. Historically aprotinin (Trasylol) was given to high risk liver transplant patients to minimise the bleeding associated with fibrinolysis. Aprotinin was withdrawn from clinical practice in 2008, and since that time treatment with antifibrinolytic therapy has generally moved towards a treatment only regime, rather than prophylaxis. Comparing retrospective propensity matched cohorts (prophylactic versus treatment only with anti-fibribrinolytics agents) the impact of fibrinolysis on transfusion requirements was investigated, and also whether the timing of the appearance of fibrinolysis at different stages of the operation has different prognostic significance. Chapter six describes the prevalence of hypercoagulability during liver transplantation, as determined by thromboelastography performed at the start of the procedure, and at various time points during the operation, in a series of 100 consecutive patients undergoing liver transplantation. This information gives an indication of the association of hypercoagulability with underlying disease aetiology, and also whether there are changes in this baseline profile, or de-novo appearance of hypercoagulability during the intraoperative period. Chapter seven describes the sequential changes in coagulation parameters (conventional coagulation tests, pro and anticoagulant factor levels, thrombin generation, and thromboelastometry (ROTEM)) in a prospective series of patients undergoing major hepatic resection. Given that the INR is frequently prolonged in the early post operative period, the question is whether this represents a true bleeding risk, as is currently assumed, or if other tests of coagulation suggest that this assumption should be re-evaluated. Chapter eight describes the efficacy in vitro of two different dose regimes of fresh frozen plasma (FFP) to correct coagulopathy, as determined by a prolonged INR, after major hepatic resection, and also the effect of FFP on viscoelastic tests in the same group of patients. These patients will frequently receive prophylactic FFP prior to procedures, but there is little data on the effect of typical dose regimes on either conventional or viscoelastic coagulation tests. This information could be of value in determining if FFP is useful, or indeed even necessary, in these patients prior to undergoing an invasive procedure. Chapter nine summarises the findings from these chapters, and discusses whether viscoelastic coagulation tests do indeed give more valuable oversight of the haemostatic profile in patients with liver disease and following major hepatic resection. Directions for future research based on these findings are also considered.
Supervisor: Fuller, Barry Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available