Table 22.

Summary of guidance statements

Question	Guidance statement
Which VTE patients are (and are not) good candidates for DOAC therapy?	DOACs are suggested as an alternative to conventional therapy for VTE treatment in patients who meet appropriate patient selection criteria. For all other patients, we suggest VTE treatment with conventional therapy. Until further data are available, we suggest avoiding DOACs for VTE in patients with antiphospholipid antibody syndrome and patients at extremes of weight. LMWH monotherapy remains first line for patients with cancer-related VTE, but DOACs may be considered in select patients unwilling or unable to receive subcutaneous injections
How should DOACs be initiated for VTE treatment?	We suggest that a thorough patient evaluation be conducted prior to DOAC initiation which should include assessment of baseline laboratory values, concomitant drug therapies, and comorbidities. We do not recommend initial DOAC therapy in patients who are hospitalized with extensive DVT or who have PE with hemodynamic instability in whom thrombolysis or thrombectomy may be indicated. We suggest that the unique characteristics of each DOAC, their distinct dosing for VTE treatment, and patient preferences should be considered when selecting a DOAC for VTE treatment
How the anticoagulant activity of DOACs be measured?	We suggest that clinicians do not routinely measure DOAC activity. If measurement of a DOAC is indicated, we suggest that clinicians use assays that are validated either locally or in a reference laboratory and that are readily available. The chosen assay should be suitable for the DOAC being used, as well as for the indication for measurement, as detailed in Table 6
How should VTE patients who require temporary interruption of DOAC therapy be managed?	For VTE patients on DOAC therapy requiring TI for an invasive procedure, we suggest a carefully constructed, thoughtful approach that emphasizes communication between the provider managing the DOAC therapy, the clinician performing the procedure, and the patient and/or caregiver about the management of the DOAC. If TI is deemed necessary, we suggest that clinicians consider the patient’s renal function, the DOAC t1/2 and the associated bleeding risk when determining timing of cessation and resumption of the DOAC. We suggest avoiding routine use of bridge therapy during DOAC interruption
How should patients with DOAC drug–drug interactions be managed?	DOAC drug–drug interaction management must be patient-specific and incorporate multiple clinical parameters, such as concomitant renal impairment, extremes of body weight or advanced age. We suggest that clinicians avoid concomitant use of dabigatran and edoxaban with a strong inducer or inhibitor of p-gp and avoid use of rivaroxaban and apixaban with combined strong inducers and inhibitors of p-gp and CYP3A4 For patients requiring concomitant DOAC therapy with a p-gp and/or CYP3A4 inhibitor, we suggest clinicians closely follow the detailed dose adjustments or avoidance provided in the product labeling. We suggest concomitant antiplatelet or NSAIDs be avoided during DOAC therapy unless the potential benefit clearly justifies the increased bleeding risk
How should patients transition between anticoagulants?	Switching from warfarin to a DOAC When switching from warfarin to dabigatran, apixaban, rivaroxaban or edoxaban, discontinue warfarin and start the DOAC when the International Normalized Ratio (INR) has decreased to <2 for dabigatran and apixaban (<3 for rivaroxaban, <2.5 for edoxaban) to avoid periods of inadequate or excessive anticoagulation. In cases where the target INR was 2.5–3.5 or higher due to recurrent VTE, initiate the DOAC when the INR is near 2.5 or the lower end of the specified range Switching from non-warfarin anticoagulant to a DOAC When switching from a DOAC to a different DOAC or from LMWH/fondaparinux to a DOAC, start the new DOAC 0–2 h prior to the next scheduled administration of the original anticoagulant and then discontinue the original anticoagulant When switching from IV UFH to a DOAC, stop the heparin infusion and begin administration of the DOAC at the time of UFH discontinuation When switching from SC UFH treatment to a DOAC, stop the SC UFH and initiate the DOAC approximately 4–5 h after the last dose of SC UFH
How should DOAC-associated bleeding be managed?	We suggest hospitals develop evidence-based antithrombotic reversal and bleeding protocols that contain clinical decision support for providers and are easy to access and use in urgent or emergent situations. We suggest that general approaches to bleed management be employed for all patients presenting with severe hemorrhage. For DOAC patients, clinicians should attempt to rapidly determine time of last DOAC ingestion and patient’s renal function to estimate remaining duration of exposure and potential utility of additional interventions. Until specific antidotes are available, we suggest clinicians consider use of non-specific reversal strategies in patient’s refractory to standard therapies. For direct Xa inhibitors, non-activated 4-Factor PCC 50 units/kg may be considered. For direct thrombin inhibitors, either 4-Factor non-activated PCC 50 U/kg or activated PCC 80 U/kg may be considered. However, it is reasonable to withhold these strategies given the associated thrombosis risk and the low quality of evidence that they are beneficial in this setting
What is an appropriate care transitions and follow-up strategy for VTE patients on DOAC therapy?	We suggest that hospitals implement systematic DOAC management and documentation processes that address appropriate patient selection, dose initiation, perioperative management, switches between anticoagulants and transitions between care settings. Whenever possible, implementation of a specialized inpatient and outpatient anticoagulation services is strongly encouraged. We also strongly recommend that clinicians utilize a DOAC discharge checklist (Table 18) to ensure all key aspects of patient care and DOAC therapy are addressed
How can patients enhance safety and efficacy of their DOAC therapy?	We suggest use of a comprehensive, multi-media educational approach with patients and families to maximize the efficacy and safety associated with anticoagulation in the VTE population. Information should be provided in the patient’s preferred language and at an appropriate level of health literacy