The impact of elective knee/hip replacement surgery and thromboprophylaxis with rivaroxaban or dalteparin on thrombin generation

SummaryTotal 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.