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Symptomatic intracranial hemorrhage in patients receiving therapy with non-vitamin K antagonist oral anticoagulant


The first non-vitamin K antagonist oral anticoagulant ( NOAC ) introduced to the market in Japan was Dabigatran ( Pradaxa ) in March 2011, and three more NOACs, Rivaroxaban ( Xarelto ), Apixaban ( Eliquis ), and Edoxaban ( Lixiana ), have since become available.

Randomized controlled trials of non-vitamin K antagonist oral anticoagulants have revealed that intracranial hemorrhage ( ICH ) occurs less frequently with NOACs compared with Warfarin ( Coumadin ).
However, the absolute incidence of ICH associated with non-vitamin K antagonist oral anticoagulants has increased with greater use of these anticoagulants.

Researchers have explored the incidence, clinical characteristics, and treatment course of patients with NOACs-associated intracranial hemorrhage.

Investigators have retrospectively analyzed the characteristics of patients with symptomatic intracranial hemorrhage receiving non-vitamin K antagonist oral anticoagulants during the period 2011-2014.

Intracranial hemorrhage occurred in 6 patients ( 5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years ).

Mean time to onset was 146.2 ± 111.5 days after starting non-vitamin K antagonist oral anticoagulants.

Five patients received Rivaroxaban and 1 patient received Apixaban. None received Dabigatran or Edoxaban.

Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis.

When therapy with non-vitamin K antagonist oral anticoagulant was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively.

Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset.

In conclusion, six symptomatic intracranial hemorrhages occurred early in therapy with non-vitamin K antagonist oral anticoagulants but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis.
The occurrence of intracranial hemorrhage during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control ( 137.8 ± 15.9 mmHg ) and HAS-BLED score less than or equal to 2.
Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent intracranial hemorrhage during therapy with non-vitamin K antagonist oral anticoagulant. ( Xagena )

Akiyama H et al, PLoS One 2015;10(7):e0132900

XagenaMedicine_2015



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