Abstract
Hematoma volume is the strongest predictor of morbidity and mortality after intracerebral hemorrhage. Protection against early hematoma growth is therefore the mainstay of therapeutic intervention for acute intracerebral hemorrhage, but the current armamentarium is restricted to early blood pressure lowering and emergent reversal for anticoagulant agents. Although intensive lowering of systolic blood pressure to <140 mmHg appears likely to prevent hematoma growth, two recent randomized trials, INTERACT-2 and ATACH-2, demonstrated non-significant trends of reduced hematoma enlargement by intensive blood pressure control, with only a small magnitude of benefit or no benefit for clinical outcomes. While oral anticoagulants can be immediately reversed by prothrombin complex concentrate, or the newly developed idarucizumab for direct thrombin inhibitor or andexanet for factor Xa inhibitors, the situation regarding reversal of antiplatelet agents is not yet quite as advanced. However, considering at most the approximately 10% rate of anticoagulant use among patients with intracerebral hemorrhage, what is most essential for patients with intracerebral hemorrhage in general is early hemostatic therapy. Tranexamic acid may safely reduce hematoma expansion, but its hemostatic effect was insufficient to be translated into improved functional outcomes in the TICH-2 randomized trial with 2,325 participants. In this context, recombinant activated factor VII (rFVIIa) is a candidate to be added to the armory against hematoma enlargement. The FAST, a phase 3 trial that compared doses of 80 and 20 μg/kg rFVIIa with placebo in 841 patients within 4 h after the stroke onset, showed a significant reduction in hematoma growth with rFVIIa treatment, but demonstrated no significant difference in the proportion of patients with severe disability or death. However, a post hoc analysis of the FAST trial suggested a benefit of rFVIIa in a target subgroup of younger patients without extensive bleeding at baseline when treated earlier after stroke onset. The FASTEST trial is now being prepared to determine this potential benefit of rFVIIa, reflecting the pressing need to develop therapeutic strategies against hematoma enlargement, a powerful but modifiable prognostic factor in patients with intracerebral hemorrhage.
Highlights
Therapeutic strategies for intracerebral hemorrhage lag a long way behind those for acute ischemic stroke (Toyoda et al, 2016)
Elevated blood pressure is quite frequently observed in acute intracerebral hemorrhage, with 75.0% of patients showing systolic blood pressure (SBP) ≥ 140 mmHg and 33.1% having SBP ≥ 160 mmHg (Qureshi et al, 2007)
The Second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) demonstrated marginally better functional outcomes for acute intracerebral hemorrhage patients with early intensive blood pressure lowering to a targeted SBP of
Summary
Therapeutic strategies for intracerebral hemorrhage lag a long way behind those for acute ischemic stroke (Toyoda et al, 2016). According to one observational study reported in 1993, patients with a hematoma volume >60 mL showed 30day mortality rates of 93% for deep hemorrhages and 71% for lobar hemorrhages. Clinical observations when computed tomographic scan was clinically applied shows that more than half of patients with acute intracerebral hemorrhage experience a gradual, smooth worsening of the neurological deficits within several hours from onset (Mohr et al, 1978; Caplan et al, 1983; Bogousslavsky et al, 1988) Such clinical data indicate the presence of a therapeutic time window from the rupture of cerebral blood vessels to hemostasis and hematoma stabilization, during which time the hematoma grows. Therapy directed at stopping bleeding as early as possible could potentially decrease mortality and improve neurological outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
