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Intracranial Bleeding

Chapter

Abstract

The non-vitamin K antagonist oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are associated with a much lower incidence of intracranial hemorrhage than warfarin. This may be due to the fact that NOACs do not affect plasma concentrations of factor VII or the complexes of tissue factor and factor VIIa that are essential for the first reaction in the coagulation cascade, whereas warfarin suppresses factor VII production even within the therapeutic range of prothrombin time-international normalized ratios (PT-INRs). Another explanation may be that there are fewer coagulation inhibition points in the coagulation cascade with NOAC treatment than with warfarin treatment, and NOACs have a trough phase, while warfarin does not. There may be differences in the sites preventing intracranial hemorrhage between thrombin inhibitors and Xa inhibitors. Data have indicated that thrombin inhibitors and Xa inhibitors more strongly suppress brain hemorrhage and subdural hematoma, respectively, than warfarin. Analysis of the results obtained for East Asians in Phase III trials showed that, though the warfarin dose was maintained at a lower level for East Asians, the incidence of intracranial hemorrhage was higher among East Asians than non-East Asians. However, when an NOAC is used instead of warfarin, there is greater reduction of the incidence of intracranial hemorrhage in East Asians than in non-East Asians. Nonsurgical measures for intracranial hemorrhage during NOAC treatment are general measures, including systolic blood pressure control to less than 140 mmHg, charcoal administration, and application of hemodialysis to remove dabigatran, and specific measures, such as coagulation factor therapy including four-factor prothrombin complex concentrate, recombinant activated factor VII, and several antidotes including idarucizumab, andexanet alfa, and ciraparantag (arapazine).

Keywords

Non-vitamin K antagonist oral anticoagulants (NOACs) Intracranial hemorrhage Antidote East Asia Coagulation cascade 

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Copyright information

© Springer Science+Business Media Singapore 2017

Authors and Affiliations

  1. 1.Department of Cerebrovascular Medicine and NeurologyNational Hospital Organization, Kyushu Medical CenterFukuokaJapan

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