Differences in urinary prothrombin fragment 1 + 2 levels after total hip replacement in relation to venous thromboembolism and bleeding events

Abstract

Background: Prothrombin fragment 1 + 2 is excreted in urine (uF1 + 2) as a result of thrombin generation and, therefore, may be a useful marker of coagulation status. Objectives: To assess uF1 + 2 levels after total hip replacement (THR) in patients with venous thromboembolism (VTE) and bleeding events. Patients/methods: This study was conducted in parallel with a prospective, dose-finding study evaluating the efficacy and safety of different doses of rivaroxaban (Xarelto®, Bayer HealthCare AG, Wuppertal, Germany) for thromboprophylaxis, relative to enoxaparin. Deep vein thrombosis was diagnosed by mandatory venography performed 5-9 days after THR, or earlier if symptomatic. Symptomatic pulmonary embolism was diagnosed by objective testing. Bleeding complications were registered and stratified into major bleeding, clinically relevant, non-major bleeding, and minor bleeding, using predefined criteria. Results: Eighty-four patients had a VTE and 57 patients had a bleeding event (n = 722). Significantly higher median uF1 + 2 levels were observed in the VTE group on day 3 after THR (P = 0.03), compared with control. Median uF1 + 2 levels were lower in the bleeding group on day 3 after THR (P = 0.005) and on the day of venography (P = 0.36), compared with control. Comparisons between the VTE and bleeding groups showed significantly lower median uF1 + 2 levels in the bleeding group on day 3 after THR and on the day of venography (P < 0.0001 and P = 0.006, respectively). Conclusions: Measurement of uF1 + 2 could provide a simple clinical test to evaluate non-invasively the intensity of coagulation activation after THR. However, further studies are required to confirm these encouraging preliminary results. © 2008 International Society on Thrombosis and Haemostasis.