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Title: The impact of total hip/knee replacement surgery and chemical prophylaxis on thrombin generation
Author: Green, L.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2011
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Total hip/knee replacement (THR/TKR) surgery is associated with an increased risk of venous thromboembolism (VTE), and extended chemical prophylaxis is standard postoperative treatment. This thesis aimed to: (1) assess the impact of THR and TKR on thrombin generation (TG), measured in vitro via the TG test, and in vivo through TG markers - prothrombin-fragment 1.2 (F1.2), thrombin:antithrombin complexes (TAT) and D-dimer (D-D); (2) assess the impact of dalteparin, rivaroxaban and dabigatran prophylaxis on TG, 24 hours after surgery; (3) compare TG between THR and TKR patients 7 weeks after surgery. Seventy patients (36 THR/34 TKR) were studied: pre-operatively (Pre-); perioperatively (Peri-); 24 hours post-operatively (Day-1); and 7 weeks after surgery (Follow-up). Once-daily dalteparin, rivaroxaban or dabigatran prophylaxis, starting 4-8 hours post-operatively, was administered to 24, 26 and 19 patients respectively, and continued for 35 and 14 days following THR and TKR respectively. TG increased significantly during surgery, with THR showing greater in vivo TG increase than TKR. From Peri- to Day-1: dalteparin patients showed highly variable in vitro TG response with no significant changes in F1.2 and TAT; rivaroxaban significantly reduced in vitro TG, F1.2 and TAT; dabigatran showed spurious results on the TG test (due to its interference with the alpha-2 macroglobulin:thrombin complex in the TG-wells and TGcalibrator) and significantly reduced TAT but not F1.2. The reduction of TAT but not F1.2 for dabigatran suggests that thrombin is generated but blocked. TG increases during THR and TKR, indicating that administering thromboprophylaxis before surgery could be beneficial in terms of preventing and/or reducing these perioperative changes. Comparisons showed that rivaroxaban consistently lowered in vitro and in vivo TG more than dalteparin, and reduced F1.2 more than dabigatran. TAT and D-D were similar between groups. At follow-up, TG had returned to Pre- values in all patients but D-D remained elevated due to ongoing wound healing.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available