Early Hematoma Expansion Research Articles

Early Hematoma Enlargement in Primary Intracerebral Hemorrhage.

Early hematoma growth is not uncommon in patients with intracerebral hemorrhage. It is a devastating complication that independently predicts poor outcome. The early hematoma enlargement is usually defined as an absolute increase in hematoma volume of greater than 33% on repeat CT scan. To date, no ideal animal model can mimic the exact pathophysiological process of early hematoma growth. This review of early hematoma enlargement in primary intracerebral hemorrhage discusses definitions, pathophysiology, risk factors, and novel treatment options aimed at improving outcomes. Novel imaging predictors such as CT angiography spot sign and CT blend sign may predict early hematoma growth in patients with intracerebral hemorrhage. Monitoring and modulation of blood pressure may improve outcomes. Rapid reduction of blood pressure to <140 mm Hg may be safe in patients with intracerebral hemorrhage.

In Models of Intracerebral Hemorrhage, Rivaroxaban is Superior to Warfarin to Limit Blood Brain Barrier Disruption and Hematoma Expansion.

Intracerebral hemorrhage (ICH) during oral anticoagulation therapy with an oral vitamin K epoxidase reductase such as warfarin is a life-threatening complication. However, whether direct oral anticoagulants (DOACs) are associated with larger hematoma volume and higher mortality rates remains controversial. We evaluated the hematoma volume and pathophysiology of ICH during anticoagulation with warfarin or rivaroxaban, an orally active direct factor Xa inhibitor. Mice were orally pretreated with rivaroxaban (10 or 30 mg/kg), warfarin (4 mg/kg), or vehicle. ICH was induced by intrastriatal collagenase-injection. Hematoma volume and neurological deficits 24 h after ICH induction were significantly decreased in the rivaroxaban-pretreated group in comparison with the warfarin-pretreated group. Rivaroxaban did not increase the hematoma volume relative to that observed for vehicle, and improved survival rate 7 days after ICH induction compared with warfarin. We evaluated blood-brain barrier (BBB) permeability 6 h after ICH induction using Evans blue spectrophotometry. Evans blue extravasation was significantly reduced in the rivaroxaban group compared with the warfarin group. To investigate the mechanism underlying hematoma expansion and BBB permeability, we focused on thrombin, a clot-derived factor and one of the major contributors to ICH-induced brain injury. To investigate the effects of anticoagulant agents on thrombin-induced injuries, human brain endothelial cells were used in membrane permeability assays. Rivaroxaban, but not warfarin, significantly mitigated the thrombin-induced increase in membrane permeability. These findings indicate that rivaroxaban decreases BBB disruption after ICH, and limits early hematoma expansion in these experimental models compared with warfarin. Our study suggests that rivaroxaban has advantages over warfarin with respect to ICH, an important complication during long-term anticoagulation therapy.

Sex differences in intracerebral hemorrhage expansion and mortality

Background and objectiveDue to conflicting results in multiple studies, uncertainty remains regarding sex differences in severity and mortality after intracerebral hemorrhage (ICH). We investigated the impact of sex on ICH severity, expansion, and mortality. MethodsWe analyzed prospectively collected ICH patients and assessed clinical variables and mortality rate. Mediation analyses were used to examine associations between sex and mortality and sex and hematoma expansion. Results2212 patients were investigated, 53.5% male. Men with ICH were younger (72 vs. 77years), had greater smoking and alcohol use, and were more likely to have hypertension, diabetes, hypercholesterolemia and coronary artery disease (all p<0.05). Lobar hemorrhages were more frequent in women (47.6% vs 38.4%, p<0.001). Male sex was a risk factor for hematoma expansion (Odd Ratio (OR) 1.7, 95% confidence interval (CI) 1.15–2.50, p=0.007). Multivariable analysis found that male sex was independently associated with 90-day mortality (OR 2.15 (95% CI 1.46–3.19), p<0.001), and one-year mortality (Hazard Ratio 1.28 (95% CI: 1.09–1.50), p=0.003). Early hematoma expansion mediated a portion of the association between sex and mortality (mediation p=0.02). ConclusionsMen with ICH experience a higher risk of both expansion and early and late mortality, even after controlling for known risk factors. Further research is needed to explore the biological mechanisms underlying these observed differences.

Predictive Value of CTA Spot Sign on Hematoma Expansion in Intracerebral Hemorrhage Patients.

Hematoma expansion (HE) occurs in approximately one-third of patients with intracerebral hemorrhage and leads to high rates of mortality and morbidity. Currently, contrast extravasation within hematoma, termed the spot sign on computed tomography angiography (CTA), has been identified as a strong independent predictor of early hematoma expansion. Past studies indicate that the spot sign is a dynamic entity and is indicative of active hemorrhage. Furthermore, to enhance the spot sign's accuracy of predicting HE, spot parameters observed on CTA or dynamic CTA were used for its quantification. In addition, spot signs detected on multiphase CTA and dynamic CTA are shown to have higher sensitivity and specificity when compared with simple standardized spot sign detection in recent studies. Based on the spot sign, novel methods such as leakage sign and rate of contrast extravasation were explored to redefine HE prediction in combination with clinical characteristics and spot sign on CTA to assist clinical judgment. The spot sign is an accepted independent predictor of active hemorrhage and is used in both secondary intracerebral hemorrhage and the process of surgical assessment for hemorrhagic risk in patients with ischemic stroke. Spot sign predicts patients at high risk for hematoma expansion.

Acute Blood Pressure Management in Intracerebral Hemorrhage: Equipoise Resists an Attack.

There are 2 competing rationales for acute blood pressure (BP) management in primary intracerebral hemorrhage (ICH). A conservative approach is predicated on the possibility that cerebral blood flow is passively dependent on perfusion pressure, whereas an aggressive approach has been hypothesized to improve outcomes via a reduction in early hematoma expansion. Although the latter is a biologically plausible hypothesis, this relationship has not been consistently demonstrated in retrospective or prospective studies, likely reflecting the fact that hematoma expansion is dependent on multiple factors, in particular the time from symptom onset to diagnostic scan, and baseline volume.1 The most effective way to address this clinical equipoise is, therefore, a randomized controlled trial of the 2 different BP management strategies. In the ATACH-II trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage II), 1000 patients were randomized to a systolic BP (SBP) target of 110 to 139 mm Hg or 140 to 179 mm Hg, after the Data Safety Monitoring Board–recommended trial suspension on the basis of a futility analysis.2 Despite a robust and early difference in achieved BP between the 2 groups, the 90-day mortality and disability rate was unaffected (38.7% versus 37.7%; P =0.84). The reasons for this lack of treatment effect are not clear. There was no effect on the frequency of hematoma expansion, although the trend was in favor …

William M. Feinberg Award for Excellence in Clinical Stroke: High Explosive Treatment for Ultra-Acute Stroke: Hype of Hope.

Proven treatments for acute stroke can be categorized by target population (ischemic stroke [IS], intracerebral hemorrhage [ICH], or both), utility (proportion of patients who can be treated), magnitude of efficacy, and cost. In general, high-cost interventions need to have high efficacy for health economic reasons; examples include intravenous alteplase, mechanical thrombectomy, and hemicraniectomy. Conversely, low-cost interventions, such as aspirin, typically have low efficacy. Having a medium-to-high efficacy intervention that was inexpensive and could be used worldwide in both IS and ICH would be a major advantage. High blood pressure (BP) is common in acute stroke and associated independently with poor functional outcome, increased death, and early recurrence (IS) and hematoma expansion (ICH).1,2 Although debated since 1985,3 it was only recently demonstrated in the INTERACT-2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2) trial that intensive BP lowering was beneficial,4 as now promoted in international guidelines.5,6 In contrast, whether BP should be lowered acutely in IS remains unclear.7–9 Nitric oxide (NO) is a diatomic gaseous molecule of nitrogen and oxygen that is highly reactive and short lived. However, it is a fundamental physiological control and defense molecule that may have been used by early organisms as far back as 3 billion years.10 In human physiology, it has vascular regulatory, neurotransmitter, anti-infection, and reproductive roles. NO is synthesized from the amino acid L-arginine by 3 enzymes: endothelial, inducible, and neuronal NO synthase. Many effects of NO are mediated through the second messenger cGMP, which is catalyzed by guanylate cyclase from guanylate triphosphate. cGMP levels may be maintained by phosphodiesterase-5 inhibitors such as dipyridamole. NO is inactivated through oxidation to nitrite then nitrate; this reaction may be reversed and it now appears that NO may be synthesized from nitrate …

Abstract WMP92: Location of Hemorrhage Predicts Hematoma Expansion and Poor Clinical Outcome

Background: Baseline volume, spot sign, and coagulation status all predict early hematoma expansion (HE) in intracerebral hemorrhage (ICH). However, the role of ICH location on HE remains unclear. We hypothesized that lobar-located ICH would facilitate HE as it provides a larger potential volume for expansion as compared to deep locations. However, due to the close proximity of critical structures and increased risk of ventricular rupture, we also hypothesized that deep ICH would have a paradoxically increased risk of mortality and morbidity. Our objective was to assess the effect of lobar vs. non-lobar hemorrhage on HE and clinical outcome. Methods: We analyzed data from the prospective multicentre PREDICT study where patients with ICH presenting to hospital under 6 hours of symptom onset received a baseline CT, CTA, 24 hour follow-up CT, and 90-d mRS. ICH location was categorized as lobar vs deep, and primary outcomes were significant HE (&gt;6mL) and poor clinical outcome (mRS &gt;3). Multivariable regression with stepwise selection was used to adjust for relevant covariates. Sensitivity analysis was conducted by expanding the inclusion criteria to include patients who died or were treated with Factor VIIa and/or surgery prior to follow-up CT. Results: Among 302 patients meeting the inclusion criteria, lobar hemorrhage was associated with increased hematoma expansion &gt;6mL (p=0.003), poor clinical outcome (p=0.011) and mortality (p=0.017). When adjusted for covariates, lobar hemorrhage independently predicted significant hematoma expansion (aOR 2.3 [95% CI: 1.2-4.4], p=0.02). Sensitivity analysis included a total of 353 patients and lobar location was no longer significantly associated with poor outcome (p=0.198). This appeared to be related to a higher proportion of IVH in the excluded population (33% Primary vs. 65% Excluded, p&lt;0.001). Conclusion: Lobar hemorrhage led to expansion and poor clinical outcome in the primary analysis population. Sensitivity analysis of the excluded population revealed that deep bleeds are associated with a higher degree of mortality and morbidity, likely due to a higher frequency of IVH. Our findings suggest that baseline ICH location should be considered for risk stratification algorithms.

Intraventricular Hemorrhage and Early Hematoma Expansion in Patients with Intracerebral Hemorrhage.

Intraventricular hemorrhage is associated with poor functional outcomes in patients with intracerebral hemorrhage (ICH). We aimed to investigate the association between intraventricular hemorrhage and early hematoma expansion in patients with ICH. Patients with ICH who underwent a baseline CT scan within six hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Univariate and multivariable logistic regression were used to assess the relationship between presence of intraventricular hemorrhage and early hematoma expansion. A total of 160 patients were included in the study. Significant hematoma growth was observed in 52 (32.5%) patients presenting within six hours after onset of symptoms. Intraventricular hemorrhage was observed in 66 (41.25%) patients with ICH. Multivariate analyses demonstrated that a short time from onset to baseline CT scan, the initial hematoma volume, and the presence of intraventricular hemorrhage on follow-up CT scan were independently associated with hematoma enlargement. The presence of intraventricular hemorrhage on follow-up CT scan can be associated with hematoma expansion in patients with ICH.

17β-Estradiol attenuates hematoma expansion through estrogen receptor α/silent information regulator 1/nuclear factor-kappa b pathway in hyperglycemic intracerebral hemorrhage mice.

17β-estradiol (E2) has been reported to reduce bleeding and brain injury in experimental intracerebral hemorrhage (ICH) model. However, it is not clear if E2 can prevent early hematoma expansion (HE) induced by hyperglycemia in acute ICH. The aim of this study is to evaluate the effects of E2 on HE and its potential mechanisms in hyperglycemic ICH mice. Two hundred, 8-week-old male CD1 mice were used. ICH was performed by collagenase injection. 50% dextrose (8 mL/kg) was injected intraperitoneally 3 hours after ICH to induce acute HE (normal saline was used as control). The time course of HE was measured 6, 24, and 72 hours after ICH. Two dosages (100 and 300 μg/kg) of E2 were administrated 1 hour after ICH intraperitoneally. Neurobehavioral deficits, hemorrhage volume, blood glucose level, and blood-brain barrier disruption were measured. To study the mechanisms of E2, estrogen receptor α (ERα) inhibitor methyl-piperidino-pyrazole, silent information regulator 1 (Sirt1) siRNA was administered, respectively. Protein expression of ERα, Sirt1, and acetylated nuclear factor-kappa B, and activity of matrix metalloproteinases-9 were detected. Hyperglycemia enhanced HE and deteriorated neurological deficits after ICH from 6 hours after ICH. E2 treatment prevented blood-brain barrier disruption and improved neurological deficits 24 and 72 hours after ICH. E2 reduced HE by activating its receptor ERα, decreasing the expression of Sirt1, deacelylation of nuclear factor-kappa B, and inhibiting the activity of matrix metalloproteinases-9. ERα inhibitor methyl-piperidino-pyrazole and Sirt1 siRNA removed these effects of E2. E2 treatment prevented hyperglycemia-enhanced HE and improved neurological deficits in ICH mice mediated by ERα/Sirt1/nuclear factor-kappa B pathway. E2 may serve as an alternative treatment to decrease early HE after ICH.

Time Course of Early Postadmission Hematoma Expansion in Spontaneous Intracerebral Hemorrhage

Early hematoma expansion (EHE) in patients with intracerebral hematoma is a promising treatment target. To date, the time course of EHE has remained poorly described. We prospectively investigated the time course of EHE. We included consecutive patients presenting spontaneous intracerebral hematoma within 4.5 hours. On admission, patients underwent noncontrast computed tomography (CT) and CT angiography. Serial hematoma volume estimations by transcranial B-mode ultrasound were effected through the contralateral transtemporal bone window by obtaining sagittal, transversal, and coronal diameter and calculating the ABC/2-formula. National Institute of Health Stroke Scale and transcranial B-mode ultrasound were performed consecutively every 30 minutes during the first 6 hours and from 6 to 12 hours every 2 hours. Follow-up CT and ultrasound were performed after ≈24 hours. Twenty-five patients with intracerebral hematoma were included; mean (SD) time from onset to CT was 108.6 (45.7) minutes. Ten (40%) patients had EHE. In patients with a final clinically significant hematoma expansion >12.5 mL, all EHE occurred within 6 hours after admission scan. EHE in spot sign positive patients continued during the first 5 hours after CT angiography. In spot sign-negative patients, no significant EHE was observed (Friedman test, P=0.476). Neurological deterioration occurred in 5 (20%) patients and was well temporally correlated with EHE. Transcranial B-mode ultrasound demonstrated good volume estimation compared with the follow-up CT with a maximum absolute volume deviation within 7 mL and minimal systematic error (mean deviation, 1.3 [confidence interval, -0.1 to 2.6] mL). EHE was reliably reflected by transcranial B-mode ultrasound and mainly occurred within the first 7 to 8 hours after symptom onset. http://www.clinicaltrials.gov. Unique identifier: NCT01472224.

Advances in CT for prediction of hematoma expansion in acute intracerebral hemorrhage

Intracerebral haemorrhage accounts for 10–15% of all strokes and is associated with high morbidity and mortality. Early hematoma expansion, which occurs in approximately a third of patients leads to worse outcomes. Prediction of expansion may aid in the identification of patients most likely to benefit from novel medical or surgical therapies. Intrahematoma contrast density seen on CT angiography, coined the ‘spot sign’, has been validated in a prospective multicenter study to predict expansion and poor outcome. Increasing the number of spot signs visualized increases the risk of expansion. Utilization of delayed or dynamic contrast-enhanced CT is able to detect up to 21% additional patients with contrast extravasation, and improves sensitivity for outcome prediction. Different patterns of contrast extravasation may indicate differential rates of hemorrhage. CT angiography or dynamic contrast-enhanced CT imaging may aid in identifying efficacious therapies in intracerebral haemorrhage, and identification ...

Computed Tomography Angiography Spot Sign Does Not Predict Case Fatality in Aneurysmal Subarachnoid Hemorrhage With Intraparenchymal Extension

Many patients with aneurysmal subarachnoid hemorrhage (SAH) with intraparenchymal extension develop early hematoma expansion, which is not explained by aneurysmal rerupture in half of cases. In patients with primary intracerebral hemorrhage, the computed tomography angiography (CTA) spot sign predicts hematoma expansion and poor outcome. We conducted a 2-center prospective cohort study to evaluate whether CTA spot sign predicts case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension. We studied consecutive patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Two experienced readers, blinded to clinical data, analyzed CTAs for spot sign presence. We assessed the proportion of patients with the CTA spot sign and tested its association with in-hospital and 90-day case fatality, using univariable and multivariable logistic regression. In 32 of 236 patients (14%), we found at least 1 spot sign. Acute surgical hematoma evacuation with aneurysm occlusion occurred in 120 patients (51%). The overall in-hospital case fatality rate was 37%. The CTA spot sign was not associated with in-hospital (multivariable odds ratio, 0.51 [95% confidence interval, 0.06-3.26]) or 90-day (multivariable odds ratio, 0.59 [0.21-1.65]) case fatality. The found frequency of CTA spot signs is lower after aneurysmal than primary intracerebral hemorrhage and is not associated with in-hospital or 90-day case fatality in patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension.

A practical prediction model for early hematoma expansion in spontaneous deep ganglionic intracerebral hemorrhage

ObjectiveEarly hematoma expansion is a known cause of morbidity and mortality in patients with intracerebral hemorrhage (ICH). The goal of this study was to identify clinical predictors of ICH growth in the acute stage. Materials and methodsWe studied 201 patients with acute (<6h) deep ganglionic ICH. Patients underwent CT scan at baseline and hematoma expansion (>33% or >12.5ml increase) was determined on the second scan performed within 24h. Fourteen clinical and neuroimaging variables (age, gender, GCS at admission, hypertension, diabetes mellitus, kidney disease, stroke, hemorrhagic, antiplatelet use, anticoagulant use, hematoma density heterogeneity, hematoma shape irregularity, hematoma volume and presence of IVH) were registered. Additionally, blood pressure was registered at initial systolic BP (i-SBP) and systolic BP 1.5h after admission (1.5h-SBP). The discriminant value of the hematoma volume and 1.5h-SBP for hematoma expansion were determined by the receiver operating characteristic (ROC) curves. Factors associated with hematoma expansion were analyzed with multiple logistic regression. ResultsEarly hematoma expansion occurred in 15 patients (7.0%). The cut-off value of hematoma volume and 1.5h-SBP were determined to be 16ml and 160mmHg, respectively. Hematoma volume above 16ml (HV>16) ([OR]=5.05, 95% CI 1.32–21.36, p=0.018), hematoma heterogeneity (HH) ([OR]=7.81, 95% CI 1.91–40.23, p=0.004) and 1.5h-SBP above 160mmHg (1.5h-SBP>160) ([OR]=8.77, 95% CI 2.33–44.56, p=0.001) independently predicted ICH expansion. If those three factors were present, the probability was estimated to be 59%. ConclusionsThe presented model (HV>16, HH, 1.5h-SBP>160) can be a practical tool for prediction of ICH growth in the acute stage. Further prospective studies are warranted to validate the ability of this model to predict clinical outcome.

Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding

Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH).This was a retrospective case-series review of patients treated with an institution-approved warfarin reversal protocol. Patients with intracranial hemorrhage and known warfarin use with an international normalized ratio (INR)>1.4 received fresh frozen plasma (FFP), vitamin K (phytonadione), and weight-based, 3-factor PCC (Profilnine® SD) dose based on the initial INR. Demographic and clinical information, the degree of and time to INR normalization, and adverse events were recorded.The thirty study patients included 19 with primary ICH, 7 with SDH, and 4 with SAH. The mean age was 72.8 (±11) years, including 11 (37%) patients ≥80years old. The median presenting INR was 2.3 (IQR 2–3.3) and post-treatment INR was 1.4 (IQR 1.3–1.5, Z score 6.4, p<0.001). Median time from PCC administration to the first follow up INR was 95 (IQR 50–140) min. No patient's INR increased by more than 0.3 over 72h. Nine patients (30%) underwent neurosurgical procedures after PCC administration and no procedure-related bleeding complication was noted. Adverse events included 3 instances of early hematoma expansion, one ischemic stroke in a patient with endocarditis on post-PCC day 1, one pulmonary embolism 5weeks after PCC treatment, and one coronary in-stent thrombosis 60days after PCC treatment. 6 patients died prior to hospital discharge of anticipated complications of their initial event, and none from identifiable thrombotic complications of PCC.A 3-factor PCC preparation (Profilnine® SD), administered with FFP and vitamin K to patients with acute warfarin-associated intracranial bleeding is a reasonable approach to urgent warfarin reversal. However, randomized, prospective trials are needed to verify the safety and clinical effectiveness of PCC administration in this population.

The analysis of initial cranial CT of early hematoma enlargement in spontaneous intracerebral hemorrhage

Objective To investigate the predictive effect of initial cranial CT on early hematoma enlargement in spontaneous intracerebral hemorrhage. Methods Three hundred patients with spontaneous intracerebral hemorrhage within 6 hours after onset were studied. Chi⁃square test and logistic regression analysis were used to detect the related factors which may indicate hematoma enlargement. Results Sixty⁃ one (20.33% ) patients presented hematoma enlargement on cranial CT. Single factor and multivariate regression analysis showed that the following factors were associated with early hematoma enlargement: early onset, uneven density hematoma, moderate and severe brain atrophy and hematoma located at the basal ganglia. Conclusion Early onset uneven density hematoma, moderate and severe brain atrophy, and hematoma at basal ganglia are the factors which may indicate early hematoma enlargement in patiens with spontaneous intracerebral hemorrhage. DOI：10.3969/j.issn.1672⁃6731.2012.03.022

Update on Intracerebral Hemorrhage

This article provides an update on the latest diagnostic and therapeutic trials relating to the management of intracerebral hemorrhage (ICH). Early hematoma expansion and worsening cerebral edema may account for delayed neurologic deterioration after ICH. Despite advances in other areas of stroke, there has been no significant improvement in the morbidity and mortality after ICH. The cause of ICH has been shifting from chronic hypertension to other etiologies. Current understanding of the pathophysiologic processes involved with hematoma expansion and the development of secondary injury after ICH has focused the treatment strategies on prevention of these potential complications. Care for the patient after ICH includes basic medical care, prevention of hematoma expansion, and treatment of potential secondary complications. Trials are underway to evaluate the effect of acute blood pressure control on hematoma expansion and the development of cerebral edema. Similarly, new surgical techniques are being explored for clot removal, and medical therapies are being developed to prevent secondary neurotoxic damage.

Blood Pressure Management and Evolution of Thrombolysis-associated Intracerebral Hemorrhage in Acute Ischemic Stroke

There is limited knowledge on the radiographic features of thrombolysis-induced hemorrhage. The factors that influence early hematoma expansion have not been elucidated. Patients presenting with a symptomatic intracerebral hemorrhage (ICH) as a result of intravenous (IV) thrombolysis with tissue plasminogen activator (tPA) for acute ischemic stroke and had noncontrast computed tomographic (CT) scans of the head were included in this retrospective study. Calculation of hematoma volumes was obtained. Analysis of covariance was used to evaluate for the effect of baseline blood pressure (BP) on initial hematoma volume and further growth. Of 267 patients who were treated with intravenous tPA for acute ischemic stroke at our facility between January 1, 2005 and December 31, 2009, 17 patients developed symptomatic ICH and were included in the final analysis. There was a positive correlation between baseline level of systolic BP after thrombolysis and initial hematoma volume (r = 0.46; P = .03) but not for the diastolic BP (r = 0.07; P = .40). There was a significant increase in mean hematoma volume expansion when comparing results between the first and second CT scans (median 9 hours, 22 minutes; 14.9 ± 19.6 cm(3) to 26.0 ± 26.7 cm(3); P = .04). There was also a negative association between the reduction of systolic BP and hematoma growth (r = -0.67; P = .02), but no correlation with change in diastolic BP (r = -0.22; P = .28). Once diagnosed, thrombolysis-induced symptomatic ICH undergoes significant early expansion in size. Systolic BP may play a role in hematoma expansion.

Imaging and clinical prognostic indicators for early hematoma enlargement after spontaneous intracerebral hemorrhage

Objective: To analyse the imaging and clinical prognostic indicators for early hematoma enlargement after spontaneous intracerebral hemorrhage (ICH).Methods: In 126 patients, spontaneous ICH was diagnosed by computed tomography (CT) within 4 hours of disease onset. Repeat CT was performed after 24 hours to detect the development of hematoma enlargement. A regression equation was obtained by first examining the significance of correlations between possible risk factors and early hematoma progression, followed by verification using multivariate stepwise regression.Results: The incidence of early hematoma enlargement after spontaneous ICH was 25.4%, and the significant prognostic indicators were CT hematoma inhomogeneity, degree of consciousness impairment on admission and time between disease onset and initial CT. In addition, the characteristic 'hematoma enlargement border' on CT has important prognostic value in early hematoma enlargement.Conclusion: Clear prognostic indicators exist for early hematoma enlargement after spontaneous ICH, suggesting that hematoma inhomogeneity has important implications for predicting ICH progression, and we discovered as well as defined the 'hematoma enlargement border', an imaging characteristic of early hematoma enlargement.

Reducing the risk of ICH enlargement

Intracerebral hemorrhage (ICH) comprises 15% of all strokes, and carries the highest risk of mortality and poor long-term outcome. ICH has long been recognized as the least treatable form of stroke, and hematoma volume as the strongest single predictor of mortality and outcome. CT-based studies have found that early substantial hematoma expansion occurs in 18-38% of patients initially scanned within 3 h of symptom onset. This finding is associated with early neurological deterioration and an increased risk of poor outcome. Ultra-early hemostatic therapy might be beneficial in preventing hematoma growth, resulting in improved mortality and neurological function. Recombinant activated factor VII (rFVIIa) promotes local hemostasis in the presence or absence of coagulopathy at sites of vascular injury, and is a promising treatment for arresting active bleeding in ICH. The safety and feasibility of this approach was confirmed in a phase IIb randomized, double-blind, placebo-controlled, dose-ranging trial of 399 patients with non-coagulopathic ICH. Administration of rFVIIa within 4 h of ICH onset resulted in a significant reduction of hematoma expansion at 24 h, and reduced mortality and improved functional outcome at 90 days. A confirmatory phase III trial (The FAST Trial) to confirm these results will complete enrollment in the end of 2006.

Lack of Evidence for an Association Between Hemodynamic Variables and Hematoma Growth in Spontaneous Intracerebral Hemorrhage

Early hematoma expansion in spontaneous intracerebral hemorrhage (ICH) is associated with worse clinical outcome. We hypothesized that hemodynamic parameters are associated with the increase in hematoma volume owing to their relationship to blood vessel wall stresses. We performed a post hoc analysis of clinical and computed tomography (CT) data from patients enrolled in a prospective observational study of ICH patients presenting within 3 hours from symptom onset. Hematoma volumes were measured at hospital arrival and at 1 and 20 hours from presentation. Blood pressure and heart rate, recorded at 19 time points between presentation and 20 hours, were used to derive hemodynamic variables. Multivariable logistic-regression models were constructed to assess the relation between hemodynamic parameters and hematoma growth, adjusted for clinical covariates. From the original study, 98 patients underwent baseline and 1-hour CT scans; of these, 65 had 20-hour CT scans. Substantial hematoma growth was observed in 28% within the first hour. Of the 65 patients not undergoing surgery within 20 hours, 37% experienced hematoma growth by 20 hours. Neither baseline or peak hemodynamic parameters nor changes in hemodynamic parameters were significantly associated with hematoma growth at either 1 or 20 hours. We found no blood pressure or heart rate parameters, individually or in combination, that were associated with hematoma growth. Our data suggest the influence of hemodynamic parameters on vessel wall stress to be an unlikely target for intervention in reducing the risk of early hematoma growth in ICH.