reversal of the effects of edoxaban on bleeding measures and biomarkers by using a 4F-PCC . 19 This important study evaluated a bleeding endpoint to the reversal effect of different doses of 4F-PCC on bleeding duration and bleeding volume following edoxaban treatment . 19 To determine clinical bleeding , the investigators performed skin biopsies with a circular punch and measured the actual volume of blood loss and duration of bleeding that occurred . The study was also impressively robust , with 110 subjects treated with edoxaban . Following anticoagulation with 60mg edoxaban , the volunteers received 4F-PCC at doses of 10 , 25 or 50IU / kg . They noted that 4F-PCC dose-dependently reversed edoxaban ’ s effects on bleeding duration and ETP , with restoration to baseline values and complete reversal at 50IU / kg . They reported that 4F-PCC dose-dependently reversed the anticoagulation effects of edoxaban with complete reversal of bleeding duration and endogenous thrombin potential , and partial reversal of prothrombin time following 50IU / kg . Of note was that edoxaban alone and in combination with 4F-PCC was safe and well tolerated in the volunteers . 19
Clinical registry From clinical reports , a registry trial is currently underway that will assess outcomes in bleeding patients or those requiring urgent care treated with DOACs and reversed with PCCs , rFVIIa , and / or haemodialysis ( http :// clinicaltrialsgov / ct2 / show / NCT01722786 ).
Additional therapies Although PCCs are important therapeutic agents , multiple therapies should be considered in the bleeding patient . Because fibrinolysis plays a major role in bleeding and coagulopathy , antifibrinolytics , including tranexamic acid , can be important additional adjunctive treatment strategies for major bleeding . 20 Tranexamic acid interferes with the binding of plasmin to fibrin and is used to treat bleeding and reduce the need for transfusion in cardiac surgery or trauma . European Heart Rhythm Association guidelines suggest tranexamic acid as an adjuvant for non-life-threatening NOAC-related bleeding based on its use in other bleeding scenarios ; however , animal
data suggest that , by itself , tranexamic acid does not affect NOAC anticoagulation , and clinical data supporting its efficacy in reversal of NOAC anticoagulation are scarce . Although tranexamic acid is not expected to reverse anticoagulation due to edoxaban or other factor Xa inhibitors , it is an important multimodal consideration for repletion in critically ill and bleeding patients , along with
10 , 21 – 23 fibrinogen measurements .
Conclusions Increasing data and reports note the role of the PCCs and other factor concentrates as important therapeutic approaches for treating bleeding
8 , 12 , 13 urgencies and emergencies . Although specific reversal strategies are under investigation for factor Xa reversal , the cost , use and availability are issues still to be determined . 9 In a life-threatening haemorrhage associated with DOACs , basic resuscitation principles should be considered , with haemodynamic and haemostatic resuscitation of patients . The role of PCCs and other adjunct factors are important multimodal factors for therapy , and in this author ’ s view , will also be important as part of therapy for life-threatening haemorrhage despite the development of the specific antidotes . 9 l
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