Anticoagulant-Associated ICH: Management Still a Challenge

Megan Brooks

August 08, 2014

Intracerebral hemorrhage (ICH) is often deadly, even more so when it occurs in patients receiving oral anticoagulant (OAC) therapy.

The challenges of managing anticoagulant-associated ICH (AAICH) are the focus of a 20-page educational supplement to the August issue of the Journal of Neurosurgery, complete with continuing medical education credits.

As the population ages and more patients are prescribed long-term therapy with anticoagulants, including warfarin and novel OACs, the number of cases of AAICH is increasing and will continue to increase, first author Peter Le Roux, MD, The Brain and Spine Center, Wynnewood, Pennsylvania, and colleagues note in their article.

The mortality rate for AAICH is "as high as 42.3% to 67%," even following prothrombin complex concentrate (PCC) therapy, they point out. This rate is substantially higher than that of ICH as a whole. "The high mortality rates may be driven, at least in part, by hemorrhage expansion, as AAICH is associated with greater expansion than spontaneous ICH," the authors say.

"Importantly, mortality due to AAICH has not improved over the last 20 years, indicating that there are barriers to AAICH treatment and room for improvement," they write.

Lack of High-Quality Data

In the article, "Race Against the Clock: Overcoming Challenges in the Management of Anticoagulant-Associated Intracerebral Hemorrhage," the authors discuss the most up-to-date information on AAICH and its treatment and highlight the urgency in reversing the effect of anticoagulant medications in patients with ICH.

Patients receiving warfarin therapy have a 7- to 10-fold increased risk of developing ICH, and warfarin-associated ICH occurs most often within the conventional international normalized ratio (INR) range of 2 to 3.5, they point out.

Data on the risk for AAICH are somewhat limited with the newer OACs, such as the direct thrombin inhibitor dabigatran (Pradaxa, Boehringer Ingelheim) and the direct factor Xa inhibitors rivaroxaban (Xarelto, Bayer Pharma/Janssen Pharmaceuticals) and apixaban (Eliquis, Pfizer/Bristol-Myers Squibb), the authors note.

Patients receiving OAC therapy who present with any type of ICH "require urgent correction of their coagulopathy to prevent hemorrhage expansion, limit tissue damage, and facilitate surgical intervention as necessary," the authors note.

They note that many therapies have been used alone or in combination to treat AAICH, including fresh frozen plasma (FFP), intravenous vitamin K, activated and inactivated PCCs, and recombinant activated factor VII.

The use of 3-factor PCC (activated and inactivated) and recombinant activated factor VII for AAICH constitutes off-label use of these therapies in the United States. However, in April 2013, the US Food and Drug Administration (FDA) approved Kcentra (a 4-factor PCC) for the urgent reversal of vitamin K antagonist anticoagulation in adults with acute major bleeding, as reported by Medscape Medical News. Plasma is the only other product approved for this use in the United States.

"However, there is a paucity of high-quality data to direct such therapy," the authors note.

They add that the most recent (2010) American Heart Association (AHA)/American Stroke Association guidelines for the management of spontaneous ICH include recommendations on reversal strategies of AAICH; however, the guidelines were written before the approval of the targeted OACs.

For all types of ICH, the key recommendations are to maintain a mean arterial pressure of less than 130 mmHg and a cerebral perfusion pressure (mean arterial blood pressure minus intracranial pressure) of at least 60 mmHg, the authors note.

They emphasize that it's "important to realize that recommendations for BP [blood pressure] control and AAICH are based on data for acute spontaneous ICH and not specifically for AAICH; hence the recommendations should be judged accordingly. Furthermore, in AAICH, when trying to maintain goal mean arterial pressure and cerebral perfusion pressure, FFP may affect volume restoration and so adversely affect blood pressure. The AHA recommends an emergent brain CT [computed tomography] scan when AAICH is suspected."

Controversial Subject

For a patient with AAICH, particularly one with warfarin-associated ICH, vitamin K (10 mg) is recommended with administration of FFP and PCCs to immediately reverse INR, restart vitamin K–dependent coagulation factor synthesis, and achieve hemostasis. Once the patient has been stabilized, the need to restart anticoagulation should be addressed, the authors say.

The best time to reinitiate OAC therapy following AAICH is a "controversial" subject, they note, and "neurosurgeons generally are more hesitant to do so than cardiologists." While the concern regarding recurrent hemorrhage is "real," it must be balanced against the risk for ischemic stroke or venous thromboembolism, and in particular pulmonary embolism, the authors write.

"The decision to restart anticoagulation should be based on the patient's medical history, physiology, and the need to balance the risk of thrombotic complications versus bleeding, either ongoing or recurrent," they note.

"The key take home message is individualization of treatment depending on the patient," Dr. Le Roux told Medscape Medical News.

The authors note that expert opinion before 2010 recommended restarting warfarin 7 to 14 days after AAICH. However, more recent publications suggest waiting 10 to 30 weeks after AAICH to restart warfarin may be more appropriate for some patients.

"Treatment of AAICH ranges from best medical therapy to aggressive management including a variety of surgical techniques…. While the role of these various techniques has been assessed in cases of spontaneous ICH, there is limited study of how surgery may influence the outcome in AAICH, and published guidelines and recommendations, in general, address non–anticoagulant-associated ICH," the authors note.

They recommend institutions develop protocols for managing AAICH, noting that the "ultimate success requires a multidisciplinary approach with consultation from the emergency department physician, pharmacist, hematologist, intensivist, neurologist, and, in some cases, the trauma surgeon."

J Neurosurg. 2014;121:1-20. Abstract

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