Assessment of microbleeding after prophylaxis with enoxaparin or rivaroxaban against venous thromboembolic disease following hip and knee surgery

Anticoagulants are recommended for prevention and treatment of venous thromboembolism (VTE); comprising deep vein thrombosis (DVT) and pulmonary embolism (PE). Without prophylaxis, DVT occurs in 10–40% of general surgical or medical patients. Patients undergoing major orthopaedic surgery are at a higher risk; without prophylaxis, 40–60% of these patients may develop VTE. Guidelines for VTE prevention recommend the routine use of thromboprophylaxis with low molecular weight heparins (LMWHs) or vitamin K antagonists (VKAs) for patients undergoing major orthopaedic surgery; however, the oral VKAs are rarely used for this indication. The American College of Chest Physicians (ACCP) guidelines currently recommend that thromboprophylaxis be continued for at least 14 days after total knee replacement (TKR), and up to 35 days after total hip replacement (THR). LMWHs are effective; however, their long-term use is limited by their parenteral route of administration. VKAs are the only licensed oral anticoagulants and, although they are effective, they have unpredictable pharmacokinetics (PK) and pharmacodynamics (PD), which are affected by drug and food interactions. As a result, VKAs require frequent monitoring and dose adjustment to ensure that their anticoagulant effects remain within the therapeutic range. Advances in the understanding of the coagulation pathway have enabled the development of novel anticoagulants targeting specific enzymes within the coagulation cascade, including Factor Xa (FXa) and Factor IIa. FXa has been identified as a particularly attractive target for effective anticoagulation: by catalysing the conversion of prothrombin to thrombin through the prothrombinase complex, one molecule of FXa results in the generation of more than 1000 thrombin molecules. Therefore, inhibition of FXa activity may block the amplification of thrombin generation, limiting thrombinmediated activation of coagulation and platelets, without affecting existing thrombin levels. Several FXa inhibitors, such as rivaroxaban, apixaban, betrixaban and edoxaban, are currently at advanced stages of development. Rivaroxaban (Bayer Healthcare AG, Wuppertal, Germany) is a novel, oral, direct FXa inhibitor in advanced development for the prevention and treatment of thromboembolic disorders. Rivaroxaban 10 mg orally once-daily (od) has recently received approval by the Therapeutic Goods Administration (TGA). Australia for the prevention of VTE in patients undergoing elective total hip or knee replacement (THR or TKR) surgery. Recent reports showed high efficacy of rivaroxaban compared to different regimen of LMWH in the prevention of VTE in patients undergoing elective total hip or knee replacement (THR or TKR) surgery. A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles. However further studies are warranted to establish the safety profile and to assess the effect of different anticoagulants on the post operative microvascular bleeding.