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  • br Anticoagulation reversal Anticoagulation may require elec

    2019-05-14


    Anticoagulation reversal Anticoagulation may require elective (as described above) or emergent reversal. Vitamin K may be administered, which substantially reduces INR within 24h; the rapidity of INR decrease depends on the route of administration and the dose [51,52]. Oral administration is preferred if there is no need for very rapid reversal because it is effective, safe, convenient, and predictable [52,53]. Doses required may range from 1mg to 10mg, keeping in mind that although the INR will decrease faster and to lower levels with higher doses, returning to therapeutic INR will be delayed and more difficult due to warfarin resistance, which may last up to a week [51,52]. Intravenous administration is the fastest route and lowers the INR within 12h. If rapid reversal is required, then this is easily achieved using prothrombin complex concentrate (PCC), which is the current preferred method of rapid reversal of warfarin and its use is preferable to fresh frozen plasma [52]. To date, there is no reversal agent for DOACs, although they are currently in development and may soon be available for clinical use [54]. First, administration of the drug should be halted and an investigation into the cause of bleeding carried out with treatment if indicated [55]. Neither vitamin K, fresh frozen plasma, nor prothrombin complex concentrate fully reverse the anticoagulant effects of DOACs, but they are used in clinical practice because of the lack of an alternative [27]. Dabigatran may be cleared relatively efficiently by dialysis [56]. Despite the absence of reversal agents, in comparative studies DOACS (except dabigatran at the higher dose) had lesser rates of bleeding than did warfarin [28–30]. In addition, DOACs are cleared reliably and quickly, and by the time a bleed occurs, their levels may already be waning [27]. There are several blood tests that when positive indicate the presence of DOACs in the blood and when normal do not infer their absence. For dabigatran, the thrombin time is a very sensitive indicator of the drug׳s presence in the blood. In addition, the PTT may be prolonged if dabigatran is present. For rivaroxaban, a prolonged PT/INR may indicate the presence of the drug. Currently, there is no reliable method to detect the presence of apixaban or edoxaban in coagulation studies. Anti-Xa levels may be used to detect the presence of the Xa inhibitors, apixaban, rivaroxaban, or edoxaban, in the blood [55]. Non-specific blood thinners, such as DDAVP and tranexamic acid, should be used because even though their efficacy is not proven, they cause little harm and may add benefit [57]. Reversal agents the focus of ongoing trials that show promise, and they may soon be available in clinical practice. Idarucizumab is a specific reversal agent for dabigatran and a recent phase III trial showed rapid and durable complete reversal [58]. Andexanet alpha is a reversal agent for factor Xa inhibitors, such as apixaban, rivaroxaban, or edoxaban, and phase two studies of this LY2584702 cost have also shown rapid complete reversal [59]. Aripazine is a reversal agent that targets all DOACs and has shown complete reversal [54].
    Management of antiplatelet drugs during pacemaker/implantable cardioverter defibrillator insertion Antiplatelet drugs are commonly used in patients who require PM/ICD insertion. Aspirin and clopidogrel are the most widely used antiplatelet drugs. A study by Tomkins et al. in patients who underwent CIED surgery showed that the risk of developing a pocket hematoma doubled when using aspirin alone, as compared to no antiplatelet medication, and was four-fold higher when comparing dual antiplatelet therapy (DAPT) to no antiplatelet [60]. A smaller study showed that approximately 18% of patients on clopidogrel developed a hematoma after PM/ICD insertion, but none of those who had clopidogrel treatment halted held for 4 days or more developed a hematoma. The risk further increased if aspirin and clopidogrel treatment were combined. Other studies have shown that clopidogrel is associated with a hematoma formation rate of 25%, compared to just 4% when its use is discontinued prior to the procedure. In addition, there was no significant difference in hematoma formation if aspirin was continued or discontinued [37]. The main necessity for dual-antiplatelet therapy arises post-insertion of coronary stents to decrease the risk of stent thrombosis and after acute coronary syndrome. The PARIS study was a two-year prospective observational study that enrolled 5018 patients to examine the effect of DAPT cessation after PCI on major adverse cardiovascular events (MACE), which is a composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularization. LY2584702 cost The results of Nondisjunction study demonstrated that 30-days, post-stent insertion, DAPT could be safely interrupted and reinitiated 14 days post procedure with no increase in MACE, including no increase in stent thrombosis [61]. However, there is still no clear consensus regarding DAPT management. An easy-to-use summary is as follows (Fig. 3): if the patient is only taking aspirin, then aspirin can be safely continued. If the patient is only on clopidogrel, then continue clopidogrel. For patients on DAPT, though the Paris study demonstrated that DAPT can be safely interrupted after 30 days, more evidence would be needed in the form of a randomized controlled trial before such a recommendation can be made. Given current evidence, the following is recommended: continue DAPT if a bare-metal stent (BMS) was inserted in the last 4 weeks and if a drug-eluting stent (DES) was implanted in the last 6 months. If more than 4 weeks/6 months have elapsed after BMS/DES implantation, respectively, then clopidogrel can be halted 5–7 days prior to the procedure and resumed as soon as possible after, while continuing aspirin [25,61,62]. Current guidelines also suggest deferring elective device implantation, if possible, until the completion of DAPT. Recommendations from recent guidelines are summarized in Table 1. There is no reliable way to reverse the effects of antiplatelet medications, other than administering platelet transfusions, and the efficacy of this approach remains under debate [63].