Monitoring of Anticoagulant Therapy after Orthopedic Surgery

Venous thromboembolism (VTE) is a serious, although decreasingly prevalent, complication following major orthopedic surgery, such as total hip replacement and total knee replacement. In Japan, patients undergoing orthopedic surgery are treated with adjusted-dose warfarin, low-dose unfractionated heparin (UFH), fondaparinux, low-molecular-weight heparin (LMWH), and edoxaban postoperatively for VTE prophylaxis. The American College of Chest Physicians guidelines recommend the administration of various anticoagulants, including warfarin, LMWH, UFH, edoxaban, fondaparinux, dabigatran, apixaban, rivaroxaban, and aspirin. Although the prothrombin time (PT) remains constant under monitoring of warfarin therapy, the PT, activated partial thromboplastin time (APTT), and anti-Xa activity may vary under monitoring of treatment with UFH, LMWH, fondaparinux, and/or novel oral anticoagulants (NOACs). Therefore, the monitoring of selective anti-Xa drugs has not yet been established. A marked prolongation of the APTT and PT values in patients treated with NOACs indicates a risk of bleeding, whereas low levels of D-dimer and soluble fibrin suggest the usefulness of anticoagulants for VTE prophylaxis. An elevation of the anti-Xa activity on day 1 in addition to a marked elevation of the D-dimer level reflect the risk of major bleeding in patients undergoing orthopedic surgery treated with fondaparinux postoperatively. However, there are currently no biomarkers for the efficacy of selective Xa or thrombin inhibitors. Therefore, it is necessary to establish further evidence for monitoring the effects of NOACs.