| Summary: | <p>Hip and knee arthroplasty are associated with significant blood loss which can exceed two litres, and 90% of patients are anaemic following arthroplasty surgery. Perioperative anaemia and allogeneic blood transfusion are associated with adverse outcomes. The aim of this thesis is to investigate strategies to minimise blood loss and perioperative anaemia in patients undergoing lower limb arthroplasty, offering improved patient outcomes and reduced healthcare costs.</p>
<p>The first study in this thesis explores the effect of perioperative anaemia on the risk of major adverse cardiac events (MACE) within 90 days of surgery. The results suggest that a lower preoperative haemoglobin, postoperative haemoglobin and nadir haemoglobin increased the risk of MACE by approximately 2% for every 1g/L decrease in haemoglobin. The odds ratio for all three haemoglobin models (preoperative Hb, postoperative Hb and nadir Hb) were found to be similar and the confidence intervals overlapped suggesting no difference between preoperative Hb, postoperative Hb and nadir Hb in terms of MACE risk.</p>
<p>It is often during the postoperative period when adverse events manifest, possibly as a result of reduced tissue oxygenation. The adoption of restrictive transfusion thresholds of 70g/L, in recognition of the adverse outcomes associated with blood transfusion, has meant that patients are being discharged with more severe anaemia. The second study of this thesis was to develop a prediction model to identify patients who are at risk of prolonged postoperative anaemia, and who do not recover their postoperative haemoglobin (Hb) levels within six weeks of arthroplasty surgery. A significant proportion of patients failed to recover their Hb levels to within 10g/L of preoperative Hb levels (41%; n=98). The developed model is based on readily available measures, including age, sex, ASA, preoperative transferrin saturation level, preoperative folate level, discharge Hb, the presence or absence of preoperative anaemia, procedure type (TKA or THA) and whether the surgery was a primary or revision procedure. Following internal validation via bootstrapping, the model showed good predictive ability with a useful R2 value of greater than 60%. The developed model will enable patients to be better counselled regarding their risk of prolonged anaemia and will identify individuals suitable for clinical trials investigating the optimal treatment for prolonged postoperative anaemia.</p>
<p>Finally, it has never been clearer to prevent bleeding and anaemia from the outset. Reducing blood loss during surgery offers the opportunity to reduce the risk of allogenic blood transfusion, reduce cost and improve patients' outcomes following surgery. There are many licenced drugs to prevent bleeding, including antifibrinolytics (Tranexamic acid, Aprotinin and Epsilon-aminocaproic acid), Desmopressin, Recombinant factor VIIa and factor XIII, Fibrinogen, Fibrin sealants and non-fibrin sealants, however it is uncertain which of these drugs is most effective at preventing bleeding, along with their optimal timing of administration, dose and route. The final study in this thesis aimed to determine the relative effectiveness of pharmacological interventions for preventing blood loss, and identify the optimal timing, dose and route of administration of pharmacological interventions. Tranexamic acid was found to be the most effective drug for reducing bleeding in hip and knee arthroplasty patients. Tranexamic acid consistently ranked higher than other treatments such as Aprotinin, EACA and topical fibrin sealants compared with placebo. Mixed routes of administration (oral and intra-articular, intravenous and intra-articular) appeared to be more effective than single routes of administration along with higher doses of tranexamic acid. This thesis recommends the use of tranexamic acid in all lower limb arthroplasty procedures.</p>
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