Intracerebral hemorrhage related to non–vitamin-K antagonist oral anticoagulants carries a high mortality and frequently involves hematoma expansion, according to a report published online Dec. 14 in JAMA Neurology.
The characteristics and natural history of acute-phase non–vitamin-K antagonist oral anticoagulant (NOAC)-associated intracerebral hemorrhage (ICH) “are largely unknown,” and there are no prospective data concerning hematoma expansion or the effectiveness of prothrombin complex concentrate in limiting that expansion by reversing anticoagulation. Nevertheless, current recommendations suggest that clinicians consider administering prothrombin complex concentrate in this patient population, said Dr. Jan C. Purrucker of the department of neurology at Heidelberg (Germany) University and his associates (JAMA Neurol. 2015 Dec 14. doi: 10.1001/jamaneurol.2015.3682).
To characterize the clinical and radiologic course, management, and outcome of NOAC-associated intracerebral hemorrhage in routine clinical practice, Dr. Purrucker and his associates performed the ICH substudy of the Registry of Acute Stroke Under New Oral Anticoagulants (RASUNOA). This is a prospective registry involving 38 neurology departments with certified stroke units across Germany. For their substudy, the investigators focused on 61 adults with a mean age of 76 years (range, 46-97 years) who were taking NOACs (apixaban [Eliquis], dabigatran etexilate [Pradaxa], or rivaroxaban [Xarelto]) and had moderate to severe neurologic deficit and a median hematoma volume of 10.8 mL at presentation. Thirty-five of these patients (57%) were treated with prothrombin complex concentrate.
Mortality was high, at 16% (10 patients) during the acute inpatient stay and 28% (17 patients) at 3 months; 65% of the survivors had an unfavorable outcome. Substantial hematoma expansion – defined as a 33% or greater relative increase or 6 mL or greater absolute increase in ICH volume – was common, affecting 38% of patients. “This proportion was within the range reported for vitamin-K antagonist–associated intracerebral hemorrhage (36%-56%) and is higher, compared with that related to intracerebral hemorrhage in patients not receiving anticoagulation (12%-26%),” the investigators wrote.
Both larger hematoma volume at baseline (odds ratio, 2.37) and intraventricular extension at baseline (OR, 8.13) strongly correlated with adverse outcomes. In contrast, prothrombin complex concentrate failed to limit lesion expansion or avert adverse outcomes. This might be because patients given the treatment tended to have more severe initial neurologic deficits and more unfavorable hematoma location than did those who weren’t given prothrombin complex concentrate. In any case, “our study design, the limited sample size, and the potential for confounding by indication do not allow any [firm] conclusions regarding a potential association between prothrombin complex concentrate treatment and outcome,” they noted.
The RASUNOA registry was supported by the University Hospital Heidelberg. Dr. Purrucker reported receiving support from Pfizer unrelated to this study, and his associates reported ties to numerous industry sources.