Median Intracerebral Hemorrhage Volume Research Articles

Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.

Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Of 44 patients analyzed, the mean age was 64years, 57% were female, and the median ICH volume was 23mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.

Short-term functional outcomes of patients with acute intracerebral hemorrhage in the native and expatriate population.

Functional outcomes in patients with intracerebral hemorrhage (ICH) have not been well characterized in the Middle East and North Africa Region. We report the 30 and 90-day clinical outcomes in the native and expatriate of Qatar with ICH. We evaluated the Glasgow Coma Scale (GCS), NIHSS, and imaging in the Qatar Stroke Registry (2013-22). The outcome measures were a modified Rankin Scale (mRS) at 90 days and mortality at 30 and 90 days. Unfavorable outcome was defined as mRS of 4-6. We performed non-parametric ROC analyses to measure the concordance index (C-index) to assess the goodness-of-fit of ICH score for predicting 30 day and 90-day mortality and functional outcome. 1,660 patients (median age of 49 (41.5-58) years; male 83.1%, expatriates 77.5%) with ICH, including supratentorial deep in 65.2%, cortical in 16.2%, infratentorial 16% and primary intraventricular in 2.5% were studied. The median baseline ICH volume was 7.5 (3.2-15.8) ml. An unfavorable outcome was seen in 673 (40.5%) patients at 90 days. The unfavorable 90-day outcome (mRS 4-6) was 49.2% in the native population vs. 44.4% in Africans, 39.0% in South Asian, 35.3% in Far Eastern, and 7.7% in Caucasians, p < 0.001. Mortality at 30 days and 90 days was 10.4 and 15.1%. Increasing age [OR (95% CI), 1.02 (1.00-1.03)], lower GCS [0.77 (0.73-0.80)], prior use of antiplatelet medications [1.82 (1.19-2.08)], higher ICH volume [1.03 (1.02-1.04)], and presence of any intraventricular hemorrhage [1.57(1.19-2.08)], were associated with unfavorable outcome. In this relatively younger ICH cohort more than 75% were expatriates. The ICH volume, 90-day unfavorable outcome and mortality was lower in the expatriates compared to the local Arab population, likely related to the younger age and smaller size of the hemorrhages. Prognostic scoring systems may have to be modified in this population to avoid early withdrawal of care.

Cognitive Outcome after Acute Spontaneous Intracerebral Hemorrhage: Analysis of the iDEF Randomized Trial

Introduction: The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH. Methods: We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90. Results: 291 were available for analysis under the trial’s modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8–18). The median baseline ICH volume was 12.9 IQR (6.4–26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p < 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score <26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery. Conclusions: Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration.

Baseline perihematomal edema, C-reactive protein, and 30-day mortality are not associated in intracerebral hemorrhage.

The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality. We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59-79), median baseline ICH volume 11.5 (IQR 4.3-28.9) mL, and median baseline CRP 2.5 (IQR 1.5-7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000-0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90-1.05, p = 0.51 and HR 0.98; 95%CI 0.93-1.03, p = 0.41, respectively). Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.

Sex Differences in Perihematomal Edema Volume and Outcome After Intracerebral Hemorrhage.

Although larger hematoma volume is associated with worse outcome after intracerebral hemorrhage (ICH), the association between perihematomal edema (PHE) volume and outcome remains uncertain, as does the impact of sex on PHE and outcome. Here we aimed to determine whether larger PHE volume is associated with worse outcome and whether PHE volume trajectories differ by sex. We conducted a post hoc analysis of the Factor VIIa for Acute Hemorrhagic Stroke Treatment (FAST) trial, which randomized patients with ICH to receive recombinant activated factor VIIa or placebo. Computerized planimetry calculated PHE and ICH volumes on serial computed tomography (CT) scans (at baseline [within 3h of onset], at 24h, and at 72h). Generalized estimating equations examined interactions between sex, CT time points, and FAST treatment arm on PHE and ICH volumes. Mixed and multivariable logistic models examined associations between sex, PHE, and outcomes. A total of 781 patients with supratentorial ICH (mean age 65years) were included. Compared to women (n = 296), men (n = 485) had similar median ICH (14.9 vs. 13.6mL, p = 0.053) and PHE volumes (11.1 vs. 10.5mL, p = 0.56) at baseline but larger ICH and PHE volumes at 24h (19.0 vs. 14.0mL, p < 0.001; 22.2 vs. 15.7mL, p < 0.001) and 72h (16.0 vs. 11.8mL, p < 0.001; 28.7 vs. 19.9mL, p < 0.001). Men had higher absolute early PHE expansion (p < 0.001) and more hematoma expansion (growth ≥ 33% or 6mL at 24h, 33% vs. 22%, p < 0.001). An interaction between sex and CT time points on PHE volume (p < 0.001), but not on ICH volume, confirmed a steeper PHE trajectory in men. PHE expansion (per 5mL, odds radio 1.19, 95% confidence interval 1.10-1.28), but not sex, was associated with poor outcome. Early PHE expansion and trajectory in men were significantly higher. PHE expansion was associated with poor outcomes independent of sex. Mechanisms leading to sex differences in PHE trajectories merit further investigation.

Abstract TMP74: Association Between Hematoma Volume After Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis

Background: Non-traumatic intracerebral hemorrhage (ICH) is independently associated with long-term increased risk of major arterial ischemic events. Whether hematoma volume influences this risk is poorly understood. Methods: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage) trials. The exposure was hematoma volume. In the primary analysis, hematoma volume was treated as a continuous measure after natural logarithmic transformation to approximate linearity, and in the secondary analysis, it was dichotomized by the median. The outcome was an ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. Results: Of 1,499 ICH patients, the mean age was 61.7 (SD, 12.8) years and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (IQR, 7.2-35.7). During a median follow up of 107 days (IQR, 91-140), 30 ischemic strokes occurred of which 22 were in patients with median ICH volume &gt; 17.3 mL with a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with median ICH volume &lt; 17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). Using adjusted Cox regression models, log-transformed ICH volume (continuous measure) was associated with an increased risk of ischemic stroke (HR, 1.5 per log-unit increase; 95% CI, 1.1-2.8). Similarly, ICH volume &gt; 17.3 mL was associated with an increased risk of ischemic stroke (HR, 2.5; 95% CI, 1.1-7.2), compared to those with an ICH volume &lt; 17.3 mL. Conclusions: In a heterogeneous cohort of ICH patients, initial hematoma volume was associated with a heightened risk of subsequent ischemic stroke.

Abstract TP158: Baseline Viscoelastic Hemostatic Assays and Associations With Poor Long-Term Intracerebral Hemorrhage Outcomes

Introduction: Viscoelastic hemostatic assays can detect coagulopathy relevant for intracerebral hemorrhage (ICH) patients at risk for hematoma expansion. However, it is unclear whether these assays associate with long term ICH outcomes. We sought to assess whether baseline coagulopathy detectable via viscoelastic hemostatic assay associates with poor 6-month neurological outcomes after ICH. Methods: Spontaneous ICH patients enrolled in a single-center prospective observational study from 2013 to 2020 who received baseline viscoelastic hemostatic assay testing via Rotational Thromboelastometry (ROTEM) were included. Patients with prior anticoagulant use were excluded. ROTEM assessments of coagulation kinetics and clot strength were the primary exposure variables. Poor 6-month neurological outcome was defined as modified Rankin Scale (mRS) 4-6. Multivariable logistic regression analyses assessed the relationships of ROTEM parameters with 6-month outcomes after adjusting for ICH score, hemoglobin, and sex. Results: Of 44 patients included for analysis, the mean age was 64, 57% were female, 52% had deep ICH, and the median ICH volume was 23.3 mL. Poor 6-month outcome was seen in 61%. We identified that slower coagulation kinetics was associated with poor 6-month outcome as assessed in both extrinsic and intrinsic pathways (EXTEM CFT: adjusted OR 1.06, 95% CI: 1.02-1.12, p=0.02; INTEM CFT: adjusted OR 1.05, 95% CI: 1.01-1.10, p=0.05, respectively). Weaker clot strength was also associated with poor 6-month outcome (EXTEM MCF: adjusted OR 0.78, 95% CI: 0.59-0.93, p=0.03; INTEM MCF: adjusted OR 0.83, 95% CI: 0.68-0.97). We did not identify similar relationships using conventional coagulation assays (ie., PT/PTT/INR, platelet count). Conclusions: We identified that baseline impaired coagulation kinetics and weaker clot strength seen using ROTEM testing associate with poor 6-month ICH outcomes. Further work is needed to clarify the generalizability of these findings and the mechanisms driving these relationships to assess whether viscoelastic guided therapies can potentially be used to improve long-term ICH outcomes.

Abstract TP171: Nationwide Diurnal Pattern Among Intracerebral Hemorrhage Incidence and Volume

Introduction: Intracerebral hemorrhage (ICH) incidence follows both seasonal and diurnal patterns noted in the literature. These differences have been attributed to variations in the coagulation cascade, blood pressure, and sleep-wake cycle that all have their own noted rhythmicity. The purpose of this analysis was to validate these trends in a large nationwide database of automated ICH detection scans and evaluate for differences in hematoma volume by image acquisition time. Methods: Serial non-contrast head CT (NCHCT) data, processed with an automated imaging software (iSchemaView), was acquired from U.S. hospitals between 1/1/2020 and 12/31/2021. Final exclusion criteria included: (1) patient age ≤ 25, (2) hematoma volume ≥ 100 ml, (3) hematoma volume ≤ 0.4 ml. Imaging time was subdivided into three epochs: (1) Night: 23:00h-06:59h, (2) Day: 07:00h-14:59h, and (3) Evening: 15:00h-22:59h. Results: A total of 19,397 scans were included in the final analysis with a median ICH volume of 2.9 ml; 15.6% of these scans had volumes above 30 ml. Peak imaging occurred around noon. Hematoma volume was significantly different across timepoints (p = 0.003), with ICHs presenting at night (average volume 14.2 ml) larger than those presenting during the day (12.9 ml, p = 0.002) or evening (13.0 ml, p = 0.012). Conclusion: In this real world, multi-site data set, we show similar diurnal trends in ICH incidence and can detect subtle differences in volume based on time of imaging. Further research is required to elucidate the potential underlying mechanisms for these differences.

Long-Term Outcomes Following Freehand Minimally Invasive Aspiration for Deep Supratentorial Intracerebral Hemorrhage: A Multicenter Cohort Study.

The aim of this study was to compare the therapeutic effects of non-navigated freehand minimally invasive aspiration and conservative medical care in patients with deep supratentorial intracerebral hemorrhage (ICH). We analyzed data from a prospective multicenter cohort study. Propensity score matching was performed to adjust for possible confounding factors. A total of 122 patients with first-onset deep supratentorial ICH with a volume ≥ 20ml were enrolled. All patients were followed up at 30days, 90days, and 1year. The mortality rate, functional outcomes, complications, and treatment costs were compared between the two groups. After propensity score matching, 122 patients with a mean age of 56.0years were included, 77.9% of whom were male. The median ICH volumes were 45.5ml in the surgery group and 48.0ml in the conservative group. The mortality rate at 30days was significantly lower in the surgery group than in the conservative group (P = 0.0127). There were no significant differences in functional outcomes at the 90-day and 1-year follow-ups between the two groups (P > 0.05). There was no significant difference in complications, including recurrent bleeding (6.6% vs. 4.9%), pulmonary infection (57.4% vs. 41.0%), deep venous thrombosis (9.8% vs. 11.5%), heart failure (1.6% vs. 6.6%), and cerebral infarction (4.9% vs. 3.3%), between the two groups. For deep supratentorial ICH, non-navigated freehand minimally invasive aspiration was safe and reduced short-term mortality but did not effectively improve long-term functional outcomes.

Peak Edema Extension Distance: An Edema Measure Independent from Hematoma Volume Associated with Functional Outcome in Intracerebral Hemorrhage.

Our objective was to test the association between hematoma volume and long-term (> 72h) edema extension distance (EED) evolution and the association between peak EED and early EED increase with functional outcome at 3months in patients with intracerebral hemorrhage (ICH). This retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. EED, an edema measure defined as the distance between the hematoma border and the outer edema border, was calculated by using absolute hematoma and edema volumes. We used multivariable logistic regression accounting for age, ICH volume, and location and receiver operating characteristic analysis for assessing measures associated with functional outcome and EED evolution. Functional outcome after 3months was assessed by using the modified Rankin Scale (0-3 = favorable, 4-6 = unfavorable). To identify properties associated with peak EED multivariable linear and logistic regression analyses were conducted. A total of 292 patients were included. Median age was 70years (interquartile range [IQR] 62-78), median ICH volume on admission 17.7mL (IQR 7.9-40.2), median peak perihemorrhagic edema (PHE) volume was 37.5mL (IQR 19.1-60.6), median peak EED was 0.67cm (IQR 0.51-0.84) with an early EED increase up to 72h (EED72-0) of 0.06cm (- 0.02 to 0.15). Peak EED was found to be independent of ICH volume (R2 = 0.001, p = 0.6). In multivariable analyses, peak EED (odds ratio 0.224, 95% confidence interval [CI] [0.071-0.705]) and peak PHE volume (odds ratio 0.984 [95% CI 0.973-0.994]) were inversely associated with favorable functional outcome at 3months. Receiver operating characteristic analysis identified a peak PHE volume of 26.8mL (area under the curve 0.695 [95% CI 0.632-0.759]; p ≤ 0.001) and a peak EED of 0.58cm (area under the curve 0.608 [95% CI 0.540-0.676]; p = 0.002) as best predictive values for outcome discrimination. Compared with absolute peak PHE volume, peak EED represents a promising edema measure in patients with ICH that is largely hematoma volume-independent and nevertheless associated with functional outcome.

Validation of the National Institutes of Health Stroke Scale in Intracerebral Hemorrhage

Background We sought to determine if the National Institutes of Health Stroke Scale (NIHSS) has a greater discriminative power than Glasgow coma scale (GCS) to identify patients at risk of poor early functional outcomes and large hematoma volumes. Methods We prospectively collected clinical assessments, imaging, and outcome data in consecutive patients with intracerebral hemorrhage, and determined the ability of GCS and NIHSS to predict poor functional outcome (modified Rankin scale 3–6) and hematoma volume &gt;30 cm 3 using receiver operating characteristics analysis, C‐statistics, and the DeLong test. Results We studied 672 patients with intracerebral hemorrhage (mean age 62±14 years; 56% men; median intracerebral hemorrhage score=1, interquartile range (IQR) 0–2; median intracerebral hemorrhage volume 7 cm 3 , IQR 2–19) with median NIHSS of 8 (IQR 3–18) and GCS 15 (IQR 7–15). NIHSS correlated strongly to GCS (r=−0.773; P &lt;0.001). Admission NIHSS (C‐statistic: 0.91; 95% CI, 0.89–0.93) predicted better than GCS (0.78; 95% CI, 0.75–0.81) discharge poor functional outcome (DeLong test P &lt;0.001). NIHSS (0.82; 95% CI, 0.78–0.86) also discriminated better than GCS (0.78; 95% CI, 0.73–0.83) patients with large hematoma volume (DeLong test P =0.029). Conclusion The NIHSS has a greater discriminative power than GCS to identify patients at risk of poor early functional outcomes and large hematoma volumes.

Associations of Cerebral Small Vessel Disease on the Features of Hematoma and Hematoma Expansion in Intracerebral Hemorrhage.

Several early noncontrast CT (NCCT) signs of spontaneous intracerebral hemorrhage (ICH) can predict hematoma expansion (HE). However, the associations of underlying cerebral small vessel disease (SVD) on early NCCT signs and HE have been less explored. We conducted an analysis of all patients with spontaneous supratentorial ICH and received follow-up imaging between 2016 and 2020 at a stroke center. The early NCCT signs were categorized as shape or density signs. HE was defined as an increase in hematoma volume ≥6 mL or 33% from baseline. The severity of SVD was assessed by both a 3-point CT-based and a 4-point magnetic resonance imaging (MRI)-based SVD score. Regression models were used to examine the associations between SVD score and hematoma volume, NCCT signs, and HE. A total of 328 patients (median age: 64 years; 38% female) were included. The median baseline ICH volume was 8.6 mL, with 38% of the patients had shape signs and 52% had density signs on the initial NCCT. Higher MRI-SVD scores were associated with smaller ICH volumes (p = 0.0006), fewer shape (p = 0.001), or density signs (p = 0.0003). Overall, 16% of patients experienced HE. A higher MRI-SVD score was inversely associated with HE (adjusted odds ratio 0.71, 95% CI: 0.53-0.96). Subgroup analysis revealed that this association was primarily observed in patients who were younger (&lt;65 years), male, had deep hemorrhage, or did not meet the criteria for cerebral amyloid angiopathy diagnosis. In patients with spontaneous ICH, a more severe SVD was associated with smaller hematoma volume, fewer NCCT signs, and a lower risk of HE. Further research is required to investigate why a higher burden of severely diseased cerebral small blood vessels is associated with less bleeding.

Abstract TP117: Temporal Serum Iron And Hemoglobin Changes In Patients From The High Dose Deferoxamine In Intracerebral Hemorrhage Trial

Introduction: Following intracerebral hemorrhage (ICH), elevated cerebral tissue iron concentrations are seen. It is unclear how peripheral serum iron concentrations change over time and how they relate to anemia after ICH. Given the known impacts of iron concentrations and anemia on clinical outcomes, we explored serum iron biomarker and hemoglobin concentration changes after acute ICH. Methods: A post hoc analysis of patients with available serial (baseline and 5 day) serum biomarker data from the multicenter, High Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF) trial was performed. Changes of serum hemoglobin, iron, transferrin, and ferritin were assessed using repeated measure ANOVA analyses. Deferoxamine treatment and poor 90 day modified Rankin Scale 4-6 were separately assessed as between subject factors for these laboratory changes. Results: Of 42 ICH patients analyzed, the mean age was 64, 62% were male, median ICH volume was 15.7mL (IQR 5.7-37.5), and baseline anemia was seen in 19%. We identified significant decrements of hemoglobin (mean difference -1.4 g/dL; 95%CI: -1.9 to -0.9; p&lt;0.0001), iron (mean difference -16.9 ug/dL; 95%CI: -29.7 to -4.1; p=0.01), transferrin (mean difference -43.9 ng/mL; 95%CI: -56.6 to -31.3; p&lt;0.0001), and conversely, significant ferritin elevations (mean difference 104.5 ug/L; 95%CI: 52.5-156.6; p&lt;0.0001) at 5 days. Anemia was identified in 43% of patients at 5 days. Deferoxamine did not have a significant impact on these repeated measures. Patients with poor long-term outcomes had greater decrements in hemoglobin compared to those with good outcomes (mean difference: -1.5 g/dL; 95%CI: -2.6 to -0.3; p=0.01). Conclusions: Serum iron and hemoglobin concentrations decrease significantly over time following ICH. Patients with worse long term ICH outcomes had greater hemoglobin decrements during their hospitalization. The aggregate iron biomarker and hemoglobin concentration changes suggest anemia development may be due to anemia of inflammation. Further work is required to address the pathophysiologic difference between systemic and central iron homeostasis mechanisms following ICH and the impacts that ICH has on inflammation, systemic iron homeostasis, anemia, and clinical outcomes.

Abstract TP125: Relationships Of Female Sex With Viscoelastic Hemostatic Assay Coagulation Characteristics After Intracerebral Hemorrhage

Introduction: There are described differences in coagulation between females and males. Specifically, female sex is associated with greater platelet activation and stronger clotting characteristics. It is unclear whether there are relevant coagulation differences identifiable between female and male patients suffering from intracerebral hemorrhage (ICH). Hypothesis: Female sex will be associated with stronger clotting characteristics on whole blood viscoelastic hemostatic assay testing. Methods: Spontaneous ICH patients admitted and enrolled into a prospective observational ICH cohort study between 2009-2020 and who received baseline viscoelastic hemostatic assay testing (Rotational Thromboelastometry: ROTEM) were assessed. Patients with prior anticoagulant use, patients receiving hemorrhage control therapies prior to ROTEM, and secondary etiologies of ICH were excluded from the analysis. Female sex was assessed as the primary exposure variable. The following ROTEM clotting parameters were assessed as the outcome: Coagulation Time (CT) and Maximum Clot Firmness (MCF). We assessed relationships of female sex with these separate ROTEM parameters using multivariable linear regression analyses after adjusting for relevant covariates. Results: Of 57 ICH patients included for analyses, mean age was 65 (SD 14.1), 47% were female, and the median ICH volume was 20.6 mL (IQR 10.1-43.3). There were no baseline intergroup sex differences in demographics, age, or ICH characteristics. Female sex was associated with increased EXTEM MCF (ß 0.323, p&lt;0.05), signifying greater clotting strength, after adjusting for age, race, baseline hematoma volume, and ICH location. Female sex was not associated with other ROTEM parameters. Conclusions: We identified that female sex was associated with stronger clotting characteristics on ROTEM viscoelastic testing. Further work is required to clarify the clinical significance of these findings and their potential specific impacts on radiographic, complication, and clinical outcomes after ICH.

Abstract TP119: Relationships Of Female Sex With Intracerebral Hemorrhage Characteristics And Outcomes

Introduction: Biological sex is known to impact cerebrovascular disease characteristics and clinical outcomes. While in intracerebral hemorrhage (ICH) it is known that biological sex impacts ICH incidence, it is less clear whether biological sex impacts ICH outcomes. Hypothesis: Female sex will be associated with ICH characteristics and clinical outcomes. Methods: Spontaneous ICH patients enrolled into a prospective observational ICH cohort study between 2009-2020 were assessed. Patients with prior anticoagulant use and secondary etiologies of ICH were excluded from the analysis. Female sex was assessed as the primary exposure variable. Primary analyses assessed relationships of female sex with radiographic outcomes: ICH location, ICH volume, hematoma expansion (&gt;33% and/or &gt;6mL). Secondary analyses assessed relationships of female sex with clinical outcomes: poor discharge neurological outcome (modified Rankin 4-6), and poor discharge disposition (skilled nursing facility, hospice, or inpatient death). Separate multivariable regression models assessed these relationships after adjusting for relevant covariates. Results: Of 504 ICH patients analyzed, mean age was 67 (SD 14.9), 46% were female, and median baseline ICH volume was 14.6 mL (IQR 4.98-35.0). In primary analyses, female sex was not associated with ICH volume or hematoma expansion but was associated with lobar ICH location (adjusted OR 1.72, 95% CI: 1.09-2.70). In secondary analyses, female sex was not associated with poor discharge neurological outcomes (adjusted OR 1.40, 95% CI: 0.74-2.64) after adjusting for race, ICH severity, and ICH location. However, there was an association of female sex with poor discharge disposition (adjusted OR 1.91, 95% CI: 1.15-3.16) after adjusting for similar covariates. Conclusions: While there were no clear intergroup sex differences in ICH severity or neurological outcomes, female sex was associated with worse discharge disposition. Further work is required to clarify whether these disposition differences are due to disease specific complications, characteristics, or if there are other social disparities responsible for these outcome differences.

Expression of DEspR in acute intracerebral hemorrhage

ObjectivesNeuroinflammation and secondary injury play a central role in the pathophysiology of intracerebral hemorrhage. The dual endothelin-1/VEGFsignal-peptide receptor (DEspR) has been reported to mediate the inflammatory response after acute brain injury in a rodent model. We performed a pilot study to assess the expression of DEspR on circulating leukocytes in patients who presented with spontaneous intracerebral hemorrhage (ICH). Materials and methodsWe performed a prospective observational study of patients presenting to two academic medical centers with ICH. Normal healthy volunteers (NHV) were also recruited for sample analysis. Whole blood was obtained, and flow cytometry was performed to examine DEspR expression on neutrophils, monocytes, and lymphocytes. ResultsA total of 19 patients were included in analysis. Median ICH volume was 39 cm3 [IQR 19 cm3, 73 cm3] and median ICH score was 2 [IQR 2, 3]. DEspR expression was more abundant on neutrophils (median 2.4% [IQR 0.5%, 5.8%], p = 0.0064) and monocytes (median 4.4% [IQR 1.7%, 15.8%], p = 0.003) relative to lymphocytes (median 0.9% [IQR 0.2%, 3.3%]). ICH patients had higher DEspR expression in all leukocytes relative to NHV (p < 0.05 for all). Among ICH patients, those with a medical history of hypertension showed higher DEspR expression on neutrophils and monocytes (p = 0.018) compared to those without hypertension. ConclusionsIn this pilot study, DEspR is expressed on circulating neutrophils and monocytes in humans after ICH, with higher levels of expression in those with hypertension. Future work in larger cohorts should examine the relationship of DEspR expression with neuroinflammatory endpoints and long-term outcome.

Cerebral small vessel disease and perihematomal edema formation in spontaneous intracerebral hemorrhage

ObjectiveBlood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of cerebral small vessel disease (cSVD)-related intracerebral hemorrhage (ICH). The formation of perihematomal edema (PHE) is presumed to reflect acute BBB permeability following ICH. We aimed to assess the association between cSVD burden and PHE formation in patients with spontaneous ICH.MethodsWe selected patients with spontaneous ICH who underwent 3T MRI imaging within 21 days after symptom onset from a prospective observational multicenter cohort study. We rated markers of cSVD (white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds) and calculated the composite score as a measure of the total cSVD burden. Perihematomal edema formation was measured using the edema extension distance (EED). We assessed the association between the cSVD burden and the EED using a multivariable linear regression model adjusting for age, (log-transformed) ICH volume, ICH location (lobar vs. non-lobar), and interval between symptom onset and MRI.ResultsWe included 85 patients (mean age 63.5 years, 75.3% male). Median interval between symptom onset and MRI imaging was 6 days (IQR 1–19). Median ICH volume was 17.0 mL (IQR 1.4–88.6), and mean EED was 0.54 cm (SD 0.17). We found no association between the total cSVD burden and EED (B = −0.003, 95% CI −0.003–0.03, p = 0.83), nor for any of the individual radiological cSVD markers.ConclusionWe found no association between the cSVD burden and PHE formation. This implies that mechanisms other than BBB dysfunction are involved in the pathophysiology of PHE.

Abstract TP131: Association Of Hemoglobin Over The First Week With Clinical Outcomes And Neuroimaging Characteristics In Patients With Spontaneous Intracerebral Hemorrhage

Introduction: Studies have shown independent associations of lower admission hemoglobin (HB) levels with larger spontaneous intracerebral hemorrhage (ICH) volumes and poor outcomes, possibly mediated by hematoma expansion (HE). Objective: We retrospectively investigated the association of HB levels over the first week post ICH with functional outcomes (FO) and neuroimaging findings in patients with spontaneous ICH (&gt;30 mL). We explored whether comorbidities modify the effects of HB. Methods: We analyzed HB levels from subjects enrolled in the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial (MISTIE III). The exposure was admission HB and the HB nadir in the first week. The primary outcome was good FO at 180 days, defined as modified Rankin Scale of 0-3. Secondary outcomes were good FO at 365 days, 30-day mortality, admission ICH volume, and HE (&gt;6 mL). Linear and logistic regression models were used to test the association of HB with clinical outcomes and neuroimaging findings. All models were adjusted for age, sex, race, treatment (medical Vs. MISTIE), Glasgow Coma Scale, ICH volume, presence of intraventricular hemorrhage, and ICH location (deep Vs. lobar). We investigated effect modification of comorbidities on association of HB with FO. Results: A total of 493 of 499 enrolled patients (61% males, mean age 61(SD=12) years, median ICH volume 41.8 (IQR=30.8-51.5) mL) were included. Patients with good FO at 180 days had a higher admission HB (13.2 Vs. 12.6 g/dl, p=0.001) and a higher nadir HB (11.7 Vs. 10.9 g/dl, p&lt;0.001). In adjusted analyses, each additional g/dl in nadir HB (but not admission HB) was associated with higher odds of good FO at 180 (OR 1.29, p=0.005) and 365 (OR 1.18, P=0.048) days. Baseline (B= -1.16, p=0.02) and nadir HB (B= -1.71, p=0.001) were inversely associated with hematoma volumes, but not with HE. There was evidence of heterogeneity in the effects of diabetes on the association of nadir HB with day 180 FO (OR 0.67; p interaction = 0.045). Conclusions: In patients with ICH &gt; 30 mL, higher nadir HB in the first week was associated with better long-term FO and smaller ICH volumes, but not with HE. Early hemoglobin changes may serve as a prognostic biomarker and a potentially modifiable factor to improve FO.

What is the median volume of intracerebral hemorrhage and is it changing?

Population-level estimates of the median intracerebral hemorrhage (ICH) volume would allow for the evaluation of clinical trial external validity and determination of temporal trends. We previously reported the median ICH volume in 1988. However, differences in risk factor management, neuroimaging, and demographics may have affected ICH volumes. The goal of this study is to determine the median volume of ICH within a population-based cross-sectional study, including whether it has changed over time. The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was a population-based study of ICH among residents of the Greater Cincinnati/Northern Kentucky region from 2008 through 2012. This study utilizes those data and compares with ICH cases from the same region in 1988. Initial computed tomography images of the head were reviewed, and ICH volumes were calculated using consistent methodology. From 2008 through 2012, we identified 1117 cases of ICH. The median volume of ICH was 14.0 mL and was lower in black (11.6) than in white (15.5) patients. Median volumes of lobar and deep ICH were 28.8 mL and 9.8 mL, respectively. Median ICH volume changed significantly from 1988 to 2008-2012, with age-and-race-adjusted volume decreasing from 18.3 mL to 13.76 mL (p = 0.025). Median volume of ICH was 13.76 mL, and this should be considered in clinical trial design. Median ICH volume has apparently decreased from 1988 to 2008-2012.

Patterns of intracerebral hemorrhage that result in unfavorable outcomes in patients with subarachnoid hemorrhage

Objective(s)Intracerebral hemorrhage (ICH) contributes considerably to the high morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH). Specific patterns of aSAH-associated ICH that are not compatible with favorable outcome remain unknown. The main objective of this study is to report patterns of aSAH-associated ICH that result in unfavorable outcomes. MethodsThis is a retrospective analysis of 1036 consecutive aSAH patients admitted to an academic neurosurgical center in a 15-year period (01/2005–12/2019). Admission imaging was investigated for presence, location and size of intracerebral hemorrhage. The rates of favorable outcome at 6 months (modified Rankin Scale) relative to ICH location and volume were analyzed to identify patterns of ICH which were incompatible with favorable outcome. Results284 of 1036 patients (27.4%) suffered from aSAH-related ICH. The median ICH volume was 14.0 ml. Outcome of patients with ICH < 10 ml was comparable to patients without ICH. ICH volumes > 10 ml were associated with worse outcomes. We identified the fronto-basal brain to tolerate even larger ICH without compromise of neurological outcomes. ICH located in the frontal, fronto-insular, temporo-insular and temporal regions were associated with intermediate prognoses as outcome declined with larger ICH volumes. ICH located in the basal ganglia, cerebellum, corpus callosum and bifrontal ICH were associated with particularly poor outcomes irrespective of ICH volumes. ConclusionaSAH-associated ICH of the basal ganglia, cerebellum, corpus callosum and bifrontal brain are associated with exceptionally poor outcomes. ICH volume alone is insufficient for prognostic considerations.