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Impact of translational medical research on haematology practice
thesisposted on 2023-05-28, 00:03 authored by Hanna, FMB
Translational Medical Research (TMR) is a relatively new research field that aims to bridge the gap between evidence-based guidelines and clinical practice. More TMR is warranted in the field of haemostatic disorders, considering limitations for easy to follow guidelines on predicting and managing venous thromboembolism (VTE). There is a gap between evidence-based guidelines and clinical practice in VTE risk prediction, prevention, or management, leading to high morbidity and mortality rates worldwide and in Australia. This thesis includes three studies that evaluate current practice against evidence-based guidelines in the field of haemostatic disorders aimed to reveal gaps in practice and provided recommendations. Study 1 presents a multicentre randomised controlled trial (RCT), which enrolled 750 participants in equal arm, parallel groups, aimed to evaluate a new protocol for VTE prevention following total hip replacement (THR) and total knee replacement (TKR) with assessment of major bleeding risk. I addressed the need to optimize VTE prophylaxis and reduce bleeding risk to improve patient safety. The newly developed and tested protocol employed a 24-hours' intermittent pneumatic calf compression followed by Rivaroxaban (direct oral anticoagulants-DOACs) versus the currently preferred subcutaneous Enoxaparin for 14 days in TKR or 35 days in THR. There were no differences in VTE risk while Rivaroxaban showed a small significant reduction in computed major bleeding risk. Study 2 presents retrospective cross-sectional data collected to outline the characteristics and management of patients presented with bleeding at a regional Australian hospital's emergency department while receiving anti-thrombotic therapy. Among the included 144 patients, I found that the numbers of warfarinised patients dominated when compared with the numbers of patients who received other anti-thrombotic therapies, whereas 47.3% of the warfarinised patients had their International Normalized Ratios above the recommended target range for their condition in the current guidelines. This suggests inadequate monitoring or compliance. DOACs-related bleeding seemed easily managed with a lesser need for reversing their anti-thrombotic effect and a shorter hospital stay when compared with patients receiving classical anticoagulants or antiplatelets. These findings might support the safety and potential cost-effectiveness of DOACs. Study 3 presents a 12-month retrospective cohort which investigated VTE risk associated with different cancer types and included 657 oncology patients. I assessed the performance of the original Khorana Score Risk Assessment Model (KS-RAM) and its six modifications, currently used in practice, in predicting VTE risk. I found limitations in these risk assessment tools in predicting VTE risk which might be attributed to limitations of including high-risk cancer types. Consequently, we developed and evaluated two VTE risk assessment models (VTE-RAM-1 and -2) using an innovative approach which demonstrated better VTE-risk prediction in cancer patients. The new VTE-RAM-1 will improve the current practice of VTE prevention in cancer patients, considering the observed improvement of VTE risk prediction and, consequently, better decision making on VTE prophylaxis. In the general conclusion, I discussed the contribution of this thesis to the TMR. I highlighted that the current practice used for VTE risk assessment, prevention, and treatment can be significantly improved to decrease VTE associated morbidity and mortality. Furthermore, I provided directions for future TMR in haemostatic disorders.
Rights statementCopyright 2021 the author Chapter 2 contains portions which are included in a pre-print version of a yet to be published Lancet article. Khalafallah, A., Hanna, F., Hyppa, A., Luttrell, E., Chilvers, C., Mathew, R., Li, R., Albarzan, A. M., Hau, R., Hayes, L., Allen Jr, J. C., Assessment of post-operative bleeding and venous thromboembolism after initial 24-hour intermittent pneumatic calf compression followed by rivaroxaban versus enoxaparin in elective hip and knee arthroplasty: a multicentre randomised controlled trial (October 27, 2018). Available at SSRN: https://ssrn.com/abstract=3276427 or http://dx.doi.org/10.2139/ssrn.3276427 Chapter 3 appears to be the equivalent of a pre-print version of a published article and has been removed from the publicly available version of the thesis. It has been published as: Hanna, F., Hyppa, A., Prakash, A., Vithanarachchi, U., Dawar, H. U., Sanga, Z., Olabode, G., Crisp, H., Khalafallah, A. A., 2021. Real-world data on characteristics and management of community patients receiving anticoagulation therapy who presented with acute bleeding to the emergency department at a regional Australian hospital: a prospective observational study, Mediterranean journal of hematology and infectious diseases, 13(1), e2021017. Copyright 2021 Institute of Hematology, Catholic University, Rome. The article is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The published article is located in appendix I.