Browsing by Author "Miller, Malcolm"

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    A Prospective, Descriptive Study Evaluating The Evolution Of Covid-19 Associated Coagulopathy In Mechanically Ventilated, Critically-Ill Patients Using Standard Laboratory Coagulation Studies And Thromboelastography
    (2023) Neethling, Colette; Miller, Malcolm; Opie Jessica
    Objectives: Few studies detail the evolution of Coronavirus disease 2019 (COVID-19) associated coagulopathy in critically-ill patients. We aimed to perform serial thromboelastography (TEG) and laboratory coagulation studies on critically-ill patients with COVID-19 over a 14-day period, comparing variables in 30-day survivors with those in non-survivors. Design: Prospective. Setting: Intensive care unit (ICU) in Cape Town, South Africa. Subjects: Forty patients with severe COVID-19 pneumonia admitted to ICU for mechanical ventilation. Interventions: None. Measurements & Main Results: On admission, TEG maximum amplitude (MA) with heparinase correction was above the upper limit of the reference range in 80% of patients while 82.5% presented with absent clot lysis. The functional fibrinogen MA was also elevated above the upper limit of the reference range in 92.5% of patients. All patients had elevated D-dimer and fibrinogen levels, prolonged prothrombin times (PT), normal platelet counts and activated partial thromboplastin times (aPTT). No significant differences in laboratory coagulation studies and TEG analysis were noted between survivors and non-survivors on admission. The heparinase MA decreased significantly with time and normalised in non-survivors on day 14 (p=0.01). The functional fibrinogen MA continued to increase in non-survivors compared to survivors on day 14 however this difference was not statistically significantly (p=0.07). No patients developed disseminated intravascular coagulation (DIC) according to the International Society on Thrombosis and Haemostasis (ISTH) after 14 days, however thrombosis and bleeding were each reported in 7.5% of patients. Conclusion: Critically-ill patients with COVID-19 admitted to ICU for mechanical ventilation were in a hypercoagulable state as demonstrated by TEG analysis. This state evolved over the 14-day observation period, emphasizing the importance of regular monitoring of coagulation parameters in these patients. A small group developed thrombotic complications despite therapeutic anticoagulation, however a similar proportion suffered a bleeding event, indicating that routine therapeutic anticoagulation should be practiced with caution.
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    An observational study to assess coagulation abnormalities in patients with elevated levels of urea and/or creatinine secondary to renal failure, presenting for renal biopsy – challenging conventional testing using visco-elastic testing
    (2018) Rodrigues, Jacques; Miller, Malcolm
    Introduction Coagulation abnormalities are well described in patients with elevated levels of urea and/or creatinine secondary to renal failure. These range from hypercoagulable to hypocoagulable states due to a range of mechanisms well described in the literature. Conventional tests of coagulation such as INR and PTT do not adequately assess these disorders of coagulation. Thromboelastography (TEG®) has proven to be a suitable alternative test of coagulation that serves as a dynamic test of global coagulation including assessment of thrombus formation as well as its breakdown. TEG® and ROTEM® assesses the visco-elastic properties of blood in vitro to define in vivo coagulability. The standard of care in our institution to assess the bleeding risk in patients with renal failure (defined by a raised urea and/or creatinine level) presenting for a renal biopsy is to use the conventional tests of coagulation, including a bleeding time if their creatinine is above 300 µmol/L. The aim of this study is to evaluate the conventional standard laboratory tests of coagulation (including a bleeding time where available), TEG® and ROTEM® in assessing coagulation disorders in patients with elevated levels of urea and/or creatinine presenting for renal biopsy. Methodology Patients with elevated levels of urea and/or creatinine presenting for a renal biopsy will be identified by the nephrology team responsible for their medical management. Prior to the renal biopsy, these patients will be approached by the study team and reviewed for inclusion into the study. Informed consent will be obtained on agreement to participate in the study. We will collect a blood sample for the TEG® and ROTEM® and this test will be performed by a laboratory technician in the Department of Anaesthesia. The clinician/nephrologist performing the biopsy will not be influenced by the outcome of these viscoelastic tests. A convenience sample of a minimum of 25 patients with renal impairment presenting for a renal biopsy will be included in this study. Results A total of 44 adult participants was entered into this observational study. Results for 1 participant were excluded from this study as their biopsy was delayed, allowing their renal function to improve and return to normal with medical management on the day that they presented for a renal biopsy. 43 patients were worked up for a renal biopsy but only 38 patients proceeded to a renal biopsy. Of these, only 31 patients had a bleeding time performed on the day of their renal biopsy. The participants ages ranged from 24 to 69 years and included 24 male and 19 female participants. Renal biopsies were cancelled by the consultant nephrologist in 5 patients on the day of their biopsy. Control samples, from 10 members in the Department of Anaesthesia, fell within the specified range of the various manufacturers. An interesting TEG® result was an average MA result of 74.22 mm (normal range 64 – 72 mm), which lies above the upper limit of normal. Two patients developed a small renal haematoma on ultrasound after the biopsy, with 1 of these patients also developing haematuria. Conclusion TEG® and ROTEM® provides a global assessment of coagulation and might be helpful in assessing coagulation defects in patients with elevated levels of urea and/or creatinine presenting for a renal biopsy, with possible extension to the surgical patient with abnormal renal function presenting for a surgical procedure to assess their risk of bleeding, especially in those who are being considered for a regional or neuraxial technique - as this could be an unacceptable risk in this population sub-group .
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    Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting
    (Public Library of Science, 2013) Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram
    Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4-6×10 10 cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale.