Conversation with Industry: Alexion Pharmaceuticals
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HCP Perspective on Managing Hematoma Expansion in Anticoagulant-Related Intracranial Hemorrhage
Join Dr Opeolu Adeoye as he shares his thoughts on predictors of hematoma expansion for an intracranial hemorrhage (ICH), the effects of hematoma expansion on ICH patient outcomes and mortality, and potential strategies to reduce the chance of ICH expansion to ensure better outcomes for patients.
Burden of Expansion: No Time for “Watch & Wait”
Perspective
Over 22,000 patients with major bleeding (taking apixaban or rivaroxaban) suffer an intracranial hemorrhage each year1-3. In non-valvular atrial fibrillation trials, there is a high mortality risk associated with factor Xa (FXa) inhibitor–related intracranial hemorrhages (ICH). In these trials, ICH-related 30-day mortality is reported at nearly 50% in FXa inhibitor–treated patients.4,5
While ICH can be caused by trauma or stroke, the primary treatment objective for a patient with an anticoagulant-related bleed should remain the same — mitigate the risks of hematoma expansion.
Currently, much of the available data regarding hematoma expansion are limited to small observational studies that are often conducted at a single center. These studies also vary considerably in their methodology for the care of patients with life-threatening bleeds, including the use of reversal or replacement agents. Based on these studies, best estimates are that hematoma expansion rates range anywhere from about 10% to 40% in DOAC-related ICH.6-9
“We are still seeing mortality rates due to expansion today which, in my opinion, are far too high”, says Dr Opeolu Adeoye, Tenured Associate Professor and Vice Chair for Research in the Department of Emergency Medicine at the University of Cincinnati (UC). As opposed to patients who are not on anticoagulants, bleeding patients on anticoagulants tend to have prolonged “trickle” types of bleeds, which “is why it is important to act with urgency in situations when patients are on an anticoagulant and are experiencing a bleed”, he says.
DOAC, direct oral anticoagulant.
FAQ: The Burden of Anticoagulant-Related Bleeding
What do we know about the overall rate of hematoma expansion among anticoagulated patients?
Currently, much of the available data regarding hematoma expansion are limited to small observational studies that are often conducted at a single center. These studies also vary considerably in their methodology for the care of patients with life-threatening bleeds, including the use of reversal or replacement agents.
Based on these studies, best estimates are that hematoma expansion rates range anywhere from around 10-40% in DOAC-related ICH6-9.
At what sites can FXa inhibitor–related major bleeds occur?
FXa inhibitor–related major bleeds can occur at several sites. These major bleeds can be bucketed into four categories: intracranial hemorrhages (ICH), bleeding at a critical site (intraocular, pericardial, intraspinal, intra-articular), bleeds resulting from major trauma (blunt or penetrating injury), and major bleeds with hemodynamic instability (gastrointestinal, retroperitoneal, genitourinary tract).10-12
Non-valvular atrial fibrillation trials for apixaban (ARISTOTLE) and rivaroxaban (ROCKET-AF) reported major bleeding by site. In ARISTOTLE, the rates of intracranial hemorrhage and gastrointestinal bleeding in the apixaban group were 0.33% per year and 0.76% per year, respectively.2 In ROCKET-AF, the rates of intracranial hemorrhage and gastrointestinal bleeding in the rivaroxaban group were 0.77% per year and 3.15% per year, respectively.3 Due to differences in trial design and patient populations, no direct comparisons between the agents can be made.
What do we know about the timing of hematoma expansion?
Currently, much of the available data regarding hematoma expansion are limited to small observational studies that are often conducted at a single center. These studies also vary considerably in their methodology for the care of patients with life-threatening bleeds, including the use of reversal or replacement agents.
In a single-center chart review of 9 intracerebral hemorrhage patients taking DOACs, 44% experienced hematoma expansion within 6 hours.9
This aligns with what is seen in clinical practice, according to Dr Adeoye, who states “In my experience, the peak of the expansion window occurs between onset of bleeding (from a patient’s perspective versus admission time) until about the 6-hour time point for patients on anticoagulants. After 6 hours, I often say that these anticoagulated patients have a prolonged “trickle” type of bleeding which may last up to 48 hours, as opposed to the large degree of expansion that occurs in the early phase of the bleeding”. In contrast, many non-anticoagulated patients aren’t “oozing” in this same fashion by 24 hours.
References
- Truven Health Analytics, DOAC Market Data Report. Data month ending November 2018.
- Patel MR et al. N Engl J Med. 2011;365(10):883-891.
- Granger CB et al. N Engl J Med. 2011;365(11):981-992.
- Held C et al. Eur Heart J. 2015;36(20):1264-1272.
- Hankey GJ et al. Stroke. 2014;45(5):1304-1312.
- Shin S et al. Neurocrit Care. 2020;32(2):407-418.
- Lioutas VA et al. Stroke. 2018;49(10) 2309-2316.
- Purrucker JC et al. JAMA Neurol. 2016;73(2):169-177.
- Melmed KR et al. J Stroke Cerebrovasc Dis. 2017;26(8):1874-1882.
- Tomaselli GF et al. J Am Coll Cardiol. 2017;70(24):3042-3067.
- Steffel J et al; Eur Heart J. 2018;39 (16):1330-1393.
- Raval AN et al. Circulation. 2017;135(10):e604-e633.
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