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Clinical and Laboratory Measurement to Improve Patient Blood Management: Foundations to the Three Pillar Framework

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Crispin, Philip

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Transfusion may be a life-saving procedure. However, history shows that the risks of transfusion have been underestimated and transfusion overused. Blood has been considered dispensable and inadequate thought given to its management, not just to prevent transfusion, but to maximise patient outcomes. Voices heralding the need for blood optimisation and conservation throughout the twentieth century have combined to develop a field known as patient blood management. Patient blood management has been described in terms of three pillars, primarily from a perioperative perspective: optimising the blood pre-operatively; minimising blood loss intraoperatively; and understanding and improving tolerance of anaemia. In this thesis I explore each pillar and argue that improving the way we measure blood-related outcomes has the potential to enhance patient blood management and the approach to transfusion therapy. Iron deficiency is the most common cause for anaemia worldwide. It is particularly common in pregnancy where it can impact the mother's quality of life, the need for transfusion and potentially have far-reaching effects for children. Despite this, there is a lack of consensus on recognising and treating it during pregnancy. I have explored the use of novel red cell and reticulocyte indices, readily available from automated blood count analysers, as tools for detecting iron deficiency. While effective, these were no better than mean cell volume, although as a screening tool, a higher cut-off value is required. I also argue that there is value is screening with ferritin during pregnancy and show that this is best applied in first trimester. Red cell transfusion guidelines advocate transfusion based on individual patient needs rather than specific haemoglobin triggers. Measuring this is difficult and most randomised studies have transfused solely based on haemoglobin. I explored tolerance of anaemia in a different light - near infrared. Near infrared spectroscopy can measure tissue oxygenation and provides a potential transfusion trigger. A systematic literature review showed that tissue oxygenation is affected by anaemia and does respond to changes in haemoglobin. However, there was too much heterogeneity to recommend routine clinical use for transfusion decisions, perhaps as it was most frequently used in acute settings where reduced blood flow is a confounding factor. I therefore explored its utility in chronic anaemia setting and with exercise to see whether poor muscle oxygenation is a limiting factor for activity in anaemia. While there was a measurable impact, there remains too much heterogeneity to identify a transfusion trigger based on tissue oxygenation. Finally, I have explored alternative strategies for managing thrombocytopenia. Platelets for transfusion are often not kept in rural and regional areas. I have shown through in vitro and transfusion studies that cryoprecipitate improves whole blood haemostasis in thrombocytopenia and should be considered as an option in bleeding patients unable to access platelet transfusions. Cryoprecipitate may be more effective than cryopreserved platelets currently under investigation. These results highlight the continuing role for research into novel ways to monitor and appropriate target treatment for the blood. They support the concept of research being included amongst a revised model of patient blood management.

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