Similarly, although thrombin time (TT) increases in the presence of a DTI, it becomes inaccurate at supratherapeutic concentrations. 10 Therefore, aPTT, PT, and INR may be tools for determining compliance with therapy or for initial detection of dabigatran during an emergent evaluation instead of quantifying a patient’s coagulopathy. 7,9 A discussion of the practical utility of these coagulation assays follows.ĭirect Thrombin Inhibitors (DTIs): Although the presence of dabigatran impacts activated partial thromboplastin time (aPTT) as well as prothrombin time (PT)/INR, the dose response with each of these assays varies, particularly at higher concentrations. Laboratory options that have been evaluated in clinical trials are summarized in TABLE 2. In certain instances, quantifying the degree of anticoagulation would be beneficial to guide reversal. However, as with warfarin, pharmacists should continue to counsel and monitor patients regarding signs and symptoms of bleeding. Newer anticoagulants promote the advantage of not requiring routine therapeutic level measurement. 7 Hemodialysis is cited as an option for dabigatran. Manufacturers suggest activated charcoal be used up to 2, 8, and 6 hours, respectively. 1 Activated charcoal may be administered to decrease the absorption of dabigatran, rivaroxaban, and apixaban. Current guidelines suggest the use of activated charcoal and dialysis for reversal of the NOACs. Withholding NOACs allows for a reversal that relies predominantly on renal clearance, as these newer agents lack specific antidotes. 6 Cautions to note with phytonadione use include anaphylaxis with IV administration and the potential for refractoriness to warfarin when warfarin is restarted. If INR is >10 with clinically significant bleeding, IV phytonadione dosed at 5 to 10 mg is indicated, as it provides a quicker INR reduction compared to oral administration. If INR is >10 with no evidence of bleeding, administering 2 to 2.5 mg of phytona-dione orally would be sufficient to reverse the effects of warfarin. Current guidelines state that no intervention is necessary for patients with an INR up to 10 and no evidence of bleeding. 6 Phytonadione may be necessary for elevated INR or for patients exhibiting signs or symptoms of bleeding. Phytonadione, exogenous vitamin K, is commonly used for rapid reversal of warfarin, with normalization of international normalized ratio (INR) typically seen within 24 hours. If rapid reversal is necessary, interventions may be warranted. With warfarin, the gradual diminishing effect on coagulation is dependent on hepatic function.
1 Anticoagulant interruption may suffice if reversal is desired in a few days to within a week. In nonurgent cases, including planned procedures, reversal of anticoagulant agents can be achieved by withholding the medication. 1 As novel oral anticoagulants (NOACs) become increasingly popular, pharmacists should be cognizant of both monitoring and reversal strategies for them, which primarily stem from the pharmacokinetic and pharmacodynamic properties of each agent as outlined in TABLE 1. These drugs work by interrupting the coagulation cascade and show similar efficacy to warfarin. 1 Newer agents, such as the direct thrombin inhibitor dabigatran and the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) have recently been introduced. Warfarin, which inhibits vitamin K epoxide reductase, preventing the formation of vitamin K–dependent clotting factors (II, VII, IX, X), had previously been the only oral anticoagulant available. The widespread use of oral anticoagulants for various conditions has resulted in the necessity to have rapid-acting reversal agents in critical situations such as life-threatening bleeds or urgent surgical procedures. As a result, healthcare providers, principally pharmacists, must be prepared to appropriately monitor and manage patients requiring reversal. While no true antidote is yet available, several promising agents are in development. Unlike warfarin, limited options currently exist for rapid reversal of novel oral anticoagulants (direct thrombin inhibitors, factor Xa inhibitors) and include fresh frozen plasma and prothrombin complex concentrates. Coagulopathy is an inherent risk for all anticoagulants, and data regarding reversal of newer agents are sparse. ABSTRACT: Oral anticoagulants are commonly prescribed for the prevention and treatment of thromboembolic disorders.
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