The impact of elective knee/hip replacement surgery and thromboprophylaxis with rivaroxaban or dalteparin on thrombin generation.
Total hip/knee replacement surgeries are associated with an increased risk of venous thromboembolism and post-operative thromboprophylaxis has become standard treatment. This study aimed to: (i) assess the impact of hip/knee replacement surgery on ex vivo thrombin generation (TG), prothrombin fragments 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer; (ii) compare the anticoagulant effects of dalteparin and rivaroxaban on TG 24 h after surgery. Haemostatic variables were assessed in plasma samples of 51 patients taken pre-operatively, peri-operatively, and 24 h post-operatively. Prophylaxis, once a day, with dalteparin or rivaroxaban, starting 6–8 h post-operatively, was administered in 25 (14 knee/11 hip) and 26 patients (13 knee/13 hip) respectively. TG, F1 + 2, TAT and D-dimer increased during surgery. Dalteparin patients showed a variable TG response 24 h after surgery: conversely, the effect of rivaroxaban on TG was consistent across individuals. Good correlation was seen between rivaroxaban levels and TG-lag-time (rs = 0·46, P = 0·01); TG-time-to-Peak (rs = 0·53, P = 0·005); TG-peak-thrombin (rs = −0·59, P = 0·001); and TG-velocity-index-rate (rs = −0·61, P = 0·0009). Patients who received rivaroxaban showed a greater decrease of TG, F1 + 2 and TAT (but not D-dimer) than those on dalteparin. TG increases during hip/knee replacement surgery. Rivaroxaban inhibits TG more than dalteparin at 24 h after surgery.
Department of Haematology, Haemostasis Research Unit, University College London Department of Orthopaedics, University College London Hospitals, London, UK. l.green@ucl.ac.uk
Laura
L
Green
Andrew S
AS
Lawrie
Shelain
S
Patel
Fahad
F
Hossain
Andrew
A
Chitolie
Ian J
IJ
Mackie
Fares S
FS
Haddad
Samuel J
SJ
Machin
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D017985:Dalteparin / Q000627:therapeutic use; D015951:Factor Xa / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use; D013917:Thrombin / Q000096:biosynthesis*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000517:prevention & control*
D000925:Anticoagulants; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban; D013917:Thrombin; D015951:Factor Xa; D017985:Dalteparin