BMS-599626 AC480 as INR values above 3 may be found despite

ll as INR values above 3 may be found despite therapeutic anticoagulation. Consequently, interpretation BMS-599626 AC480 of PT results would require specific calibration curves, the knowledge of the assay used to measure PT, and the exact timing of drug intake and blood sampling. This is in strict contrast to PT or INR measurements during vitamin K antagonist therapy, where values remain fairly constant during the day and an INR range between 2 and 3 indicates adequate VKA treatment, while values outside of this range indicate a sub or supratherapeutic anticoagulant effect of VKA. Therefore, PT or INR monitoring is not recommended with oral FXa inhibitors. However, new tests are currently being implemented to allow for exact quantification of oral direct FXa inhibitors, based on the measurement of anti FXa activity via chromogenic FXa assays.
48 52 In contrast to the oral direct FXa inhibitors, dabigatran 17-DMAG as a direct thrombin inhibitor significantly alters partial thromboplastin time and, to a lesser extent, PT and INR values. Again, these changes must not be interpreted in a similar way to heparin or VKA therapy, because test results do not necessarily correlate with dabigatran therapy. Specific tests such as HemoClot are available to monitor dabigatran therapy.53 Taken together, neither normal nor abnormal test values of PTT, PT, INR, or clotting times give any indication of the quality of NOAC therapy, and interpretation of test results needs to reflect type and dosage of NOAC, interval between submit your manuscript | www.dovepress.
com Dovepress Dovepress 144 Werth et al Therapeutics and Clinical Risk Management 2012:8 intake and blood sampling, and renal and hepatic function. However, routine monitoring is not necessary for NOAC therapy, and specific tests will be available for the rare situations when management of emergency situations requires exact quantification of NOAC activity. Management of bleeding complications In Phase II, all NOACs exhibited a broad therapeutic window with only a slight increase in bleeding complications with higher dosages in dose escalating studies in MOS.43,54 56 These results were supported in large Phase III trials, where severe bleeding complications were rare. Consequently, most bleeding complications seen after MOS will not relate to the anticoagulant in use but rather to patient specific factors or surgical complications.
Furthermore, most bleeding complications will present as nonsevere bleeding, which can simply be managed by reducing or interrupting NOAC prophylaxis for a short period of time. Because all NOACs are short acting with half lives comparable with LMWH prophylaxis, no change of standard of care is necessary in nonsevere bleeding situations. Obviously, standard management of bleeding complications may include local compression, surgical, endoscopic, or interventional therapy as well as hemodynamic stabilization with fluids or whole blood transfusions. In cases of severe bleeding, oral FXa inhibitor activity may be antagonized using prothrombin complex concentrates, recombinant factor VIIa, or factor eight inhibitor bypassing activator. Recombinant factor VII or FEIBA/aPCC may also be considered as treatment options in severe bleeding complications of dabigatrantreated patients.57,58 In case of suspected or suicidal overdosing of oral FXa inhibitors, gastrointestinal uptake can be reduced by activated carbon application within 3 hours after intake. In contrast, in patients receiving dabigatran, hemod