The effects of antithrombotic therapy on head trauma and its management

The number of patients with traumatic intracranial hemorrhage (tICH) that are taking antithrombotics (ATs), antiplatelets (APs) and/or anticoagulants (ACs), has increased, but the influence of it for outcome remains unclear. This study aimed to evaluate an influence of AT for tICH. We retrospectively reviewed all patients with tICH treated between 2012 and 2019, and analyzed demographics, neurological status, clinical course, radiological findings, and outcome data. A total of 393 patients with tICH were included; 117 were on AT therapy (group A) and 276 were not (group B). Fifty-one (43.6%) and 159 (57.6%) patients in groups A and B, respectively, exhibited mRS of 0–2 at discharge (p = 0.0113). Mortality at 30 days was significantly higher in group A than in group B (25.6% vs 16.3%, p = 0.0356). Multivariate analysis revealed that higher age (OR 32.7, p < 0.0001), female gender (OR 0.56, p = 0.0285), pre-injury vitamin K antagonist (VKA; OR 0.42, p = 0.0297), and hematoma enlargement (OR 0.27, p < 0.0001) were associated with unfavorable outcome. AP and direct oral anticoagulant were not. Hematoma enlargement was significantly higher in AC-users than in non-users. Pre-injury VKA was at high risk of poor prognosis for patients with tICH. To improve outcomes, the management of VKA seems to be important.

Clinical Strategies Against Early Hematoma Expansion Following Intracerebral Hemorrhage

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 &lt;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.

Artificial Intelligence Can Effectively Predict Early Hematoma Expansion of Intracerebral Hemorrhage Analyzing Noncontrast Computed Tomography Image

This study aims to develop and validate an artificial intelligence model based on deep learning to predict early hematoma enlargement (HE) in patients with intracerebral hemorrhage. A total of 1,899 noncontrast computed tomography (NCCT) images of cerebral hemorrhage patients were retrospectively analyzed to establish a predicting model and 1,117 to validate the model. And a total of 118 patients with intracerebral hemorrhage were selected based on inclusion and exclusion criteria so as to validate the value of the model for clinical prediction. The baseline noncontrast computed tomography images within 6 h of intracerebral hemorrhage onset and the second noncontrast computed tomography performed at 24 ± 3 h from the onset were used to evaluate the prediction of intracerebral hemorrhage growth. In validation dataset 1, the AUC was 0.778 (95% CI, 0.768–0.786), the sensitivity was 0.818 (95% CI, 0.790–0.843), and the specificity was 0.601 (95% CI, 0.565–0.632). In validation dataset 2, the AUC was 0.780 (95% CI, 0.761–0.798), the sensitivity was 0.732 (95% CI, 0.682–0.788), and the specificity was 0.709 (95% CI, 0.658–0.759). The sensitivity of intracerebral hemorrhage hematoma expansion as predicted by an artificial intelligence imaging system was 89.3%, with a specificity of 77.8%, a positive predictive value of 55.6%, a negative predictive value of 95.9%, and a Yoden index of 0.671, which were much higher than those based on the manually labeled noncontrast computed tomography signs. Compared with the existing prediction methods through computed tomographic angiography (CTA) image features and noncontrast computed tomography image features analysis, the artificial intelligence model has higher specificity and sensitivity in the prediction of early hematoma enlargement in patients with intracerebral hemorrhage.

The Effects of Antithrombotic Therapy on Head Trauma and its Management

To examine the effects of antithrombotics for head trauma, 393 consecutive patients were enrolled. The patients were divided into those that were (group A, n = 117) and were not (group B, n = 276) taking antithrombotics, and the groups’ outcomes were compared. To identify factors that affected functional independence in group A, clinical factors were compared between the patients that exhibited mRS of 0–2 and 3–6 at discharge. Furthermore, to assess the optimal time to restart antithrombotics, cases in which rebleeding occurred after antithrombotics were restarted or thromboembolic events occurred were extracted. The ratio of mRS 3–6 and death within 30 days were significantly higher in group A than in group B. Multivariate analysis of group A revealed that being aged ≥ 70, not receiving antiplatelet therapy, and intracranial hematoma enlargement were poor prognostic factors. Five patients in group A experienced ischemic strokes within 30 days. In 3 of these patients, the ischemic strokes occurred before antithrombotics were restarted. Rebleeding occurred in two cases after anticoagulants restarted within 48 hours. Patients taking antithrombotics are at high risk of poor prognosis after head trauma. To prevent thromboembolic events, the active resumption of antithrombotics after 48 hours is desirable if hemostasis has been achieved.

Abstract P424: Hemorrhage Enlargement in the First Two Hours: A Mobile Stroke Unit Study

Objective: Hematoma enlargement (HE) occurs after spontaneous intracerebral hemorrhage (ICH) but no studies have evaluated the frequency of HE in first 1-2 h after symptom onset. We evaluated HE in the first 2h after onset using a mobile stroke unit (MSU). Methods: Patients with spontaneous ICH within 4.5h were evaluated on the Houston MSU between 5/2014 and 4/2020. Baseline CT scans from the MSU were compared with scans repeated within 1h [median 67min (IQR 57-82 min]. Significant HE was defined as >6 ml if baseline volume was <20 ml and 30% increase if baseline volume >20 ml. Kruskal-Wallis and Wilcoxon rank sum tests evaluated differences in baseline volumes and HE. Intraclass correlation coefficient (ICC) evaluated agreement between two ICH measurement techniques (ABC/2 vs semi-automated). Results: 163 patients had baseline CTs, of whom 60 had repeat 1h CTs (table 1). There was no difference between baseline volume and time of CT from symptom onset {<1h vs 1-2h vs >2h median (IQR) = 14 ml (6-28) vs. 16 ml (7-32) vs. 12 ml (4-24), P=0.42)}. There was also no correlation between time from onset and difference in volume between baseline and 1 h repeat imaging. However, 9/60 patients had significant HE from baseline to 1 h repeat imaging; all of these occurred in patients initially imaged within 2 h of onset (6/24 within 1h, 3/20 within 1-2h) (P=0.03) (figure 1). High reliability was seen between the two methods measuring volumes (ICC = 0.84). Conclusion: Significant HE in the next hour occurs in 25% of ICH patients imaged within the first hour after symptom onset, and 17% imaged between 1-2 hours of onset. These patients would be a target for ultra-early hemostatic intervention.