New Guidance on Managing Anticoagulant-Associated ICH

Megan Brooks

February 27, 2015

In the acute phase of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH), two factors can protect against hematoma enlargement: getting the international normalized ratio (INR) below 1.3 and getting the systolic blood pressure (BP) below 160 mm Hg within 4 hours, a new study shows.

Anticoagulation should be reversed "as soon as possible to reduce chances for hematoma enlargement, and systolic BP levels of <160 mm Hg showed additional positive associations with reduced rates of hematoma enlargement," lead investigator Hagen Huttner, MD, from the University of Erlangen-Nuremberg, Germany, told Medscape Medical News.

The study also found that after the acute phase, restarting OAC led to significantly fewer ischemic complications during follow-up compared with not restarting OAC, without an increase in rates of recurrent ICH.

The study was published in the February 24 issue of JAMA.

Answering Unsettled Questions

"Two of the most pressing unsettled questions" about OAC-ICH are how to prevent hematoma enlargement and how to manage anticoagulation in the long-term, the authors note. "Consensus exists that elevated [INR] levels should be reversed to minimize hematoma enlargement, yet mode [of reversal], timing, and extent of INR reversal are unclear. Valid data on safety and clinical benefit of OAC resumption are missing and remain to be established."

To investigate, Dr Huttner and colleagues conducted a retrospective cohort study of patients with OAC-ICH treated at 19 German tertiary care centers between 2006 and 2012. They had 1176 patients available for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption.

Hemorrhage enlargement occurred in 307 (36.0%) of 853 patients. Reduced rates of hematoma enlargement were associated with reversal of INR levels lower than 1.3 within 4 hours of hospital admission (19.8% vs 41.5% with INR ≥1.3) and systolic BP lower than 160 mm Hg at 4 hours of admission (33.1% vs 52.4% with higher systolic BP).

The combination of INR reversal to below 1.3 within 4 hours and systolic BP of less than 160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (18.1% vs 44.2% not achieving these two values) and lower rates of in-hospital death (13.5% vs 20.7%).

In the longer term, resumption of OAC was associated with a lower risk for ischemic events.

In the study, OAC was resumed in 172 (23.9%) of 719 survivors. These patients had fewer ischemic complications (5.2% vs 15.0% with no OAC), without significantly different hemorrhagic complications (8.1% vs 6.6%).

"From a practical point of view," Dr Huttner said, "the findings may help physicians during acute phase such that systolic BP levels should be kept under 160 mm Hg and INR should be reversed as [completely] and fast as possible to stop hematoma enlargement.

"Further, our data may guide physicians in the long-term management, such that surviving patients should restart anticoagulation. However, latter findings should be assessed in large randomized controlled trials, preferably using the new direct oral anticoagulants, to weigh incidences and clinical impacts of ischemic versus hemorrhagic complications," Dr Huttner said. Such a study will start in Germany this year, he added.

Best Evidence Yet

Commenting on the study for Medscape Medical News, Alejandro A. Rabinstein, MD, from the Mayo Clinic in Rochester, Minnesota, said, "the findings regarding anticoagulant reversal and [BP] control, measures to try to minimize the risk of hematoma expansion, are mostly confirmatory results of practice [and] the best evidence yet showing that rapid reversal of anticoagulation in warfarin-related hemorrhage is effective."

In the longer term, Dr Rabinstein noted there has been "enormous speculation as to whether it is better to restart or not restart anticoagulation, particularly when you have an option. This study provides strong suggestive evidence that you should." Even with the study's limitations, the data are "so much better than the evidence out there. This is good hypothesis-generating data for a randomized controlled trial."

The study was supported by a research grant from the Johannes and Frieda Marohn Foundation, University of Erlangen, Germany. Dr Huttner has received speaker honoraria and travel grants from Boehringer Ingelheim and Bayer Healthcare. A complete list of author disclosures is listed with the original article. Dr Rabinstein has disclosed no relevant financial relationships.

JAMA. 2015;313:824-836. Abstract


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