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 December 14 in JAMA Neurology.1
The characteristics and natural history of acute-phase non–vitamin-K antagonist oral anticoagulant (NOAC)-associated intracerebral hemorrhage “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.1
Dr Purrucker and his associates performed the ICH substudy of the Registry of Acute Stroke Under New Oral Anticoagulants (RASUNOA), a prospective registry with certified stroke units in Germany. For their substudy, the investigators focused on 61 adults with a mean age of 76 years (range, 46-97 years) who were taking novel anticoagulants (NOACs; [apixaban, dabigatran etexilate, or rivaroxaban]) and had moderate to severe neurologic deficits and a median hematoma volume of 10.8 mL at presentation. Prothrombin complex concentrate was given to 35 (57%).
Mortality was high; 10 (16%) patients died during the acute inpatient stay and 17 (28%) at 3 months. Of the survivors, 65% had an unfavorable outcome. Substantial hematoma expansion—defined as a 33% or greater relative increase or 6 mL or greater absolute increase in intracerebral hemorrhage volume—affected 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 researchers wrote.
Both larger hematoma volume at baseline (odds ratio [OR], 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 were not 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.
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Hematoma Expansion Was Likely 100%
It is important to note that in the study by Dr Purrucker and his colleagues, the median time from symptom onset to the first brain imaging was 14 hours and that fully 25% of patients presented for treatment more than 22 hours after noticing their initial symptoms. In contrast, patients with spontaneous hypertensive intracerebral hemorrhage present much earlier, usually within 6 hours. This indicates that the bleeding in NOAC-associated hemorrhagic stroke often is gradual and prolonged, an “oozing” process rather than the explosive type of process seen in spontaneous hemorrhagic stroke.
It is almost certain that if this cohort had undergone imaging at 3 hours rather than at 14 hours after symptom onset, the frequency of hematoma expansion would have approached 100% rather than 38%.
Dr Stephan A. Mayer is at Mount Sinai University, New York. He reported having no relevant financial disclosures. Dr Mayer made these remarks in an editorial accompanying Dr Purrucker’s report (Mayer, SA. Emergency Reversal of Novel Oral Anticoagulants. Help Is on the Way. JAMA Neurol. doi:10.1001/jamaneurol.2015.3884).
FDA Approves Treatment for Chemotherapy, Overdoses, Life-threatening Toxicities
BY ELIZABETH MECHCATIE
Frontline Medical News
Uridine triacetate, a pyrimidine analogue, has been approved for the emergency treatment of fluorouracil or capecitabine overdoses in adults and children, and for patients who develop “certain severe or life-threatening toxicities within 4 days of receiving” these treatments, the Food and Drug Administration (FDA) announced on December 11, 2015.
“Today’s approval is a first-of-its-kind therapy that can potentially save lives following overdose or life-threatening toxicity from these chemotherapy agents,” Dr Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in the FDA statement.1 It will be marketed as Vistogard by Wellstat Therapeutics.
Uridine comes in an oral granule formulation that can be mixed into soft foods or, when necessary, administered via a nasogastric or gastrostomy tube, the prescribing information states. The indication is for use after an overdose “regardless of the presence of symptoms,” and for treating “early-onset, severe, or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (eg, gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration,” according to the prescribing information.