Total Intracranial Hemorrhage Research Articles

Stains therapy and the risk of all bleeding and intracranial hemorrhage: A meta-analysis of randomized controlled studies.

Statins had been used as a cornerstone in the primary and secondary prevention of cardiovascular disease. Widespread attention had been given to the risk of bleeding, especially intracranial hemorrhage (ICH) in patients receiving statins therapy. This study aimed to determine whether statins treatment was associated with the risk of bleeding and ICH in randomized controlled trials (RCTs). Electronic databases were searched for studies up to September 8, 2022. Articles from RCTs were included in the meta-analysis if they reported the bleeding events associated with the treatment of statins or placebo/nonstatin treatment. The risk ratios (RR) of total bleeding and ICH were pooled from the number of patients with each outcome in the statins and control groups from the included studies. Twenty-nine studies comprising 145,929 individuals (2437 incident bleeding cases) were included in the meta-analysis. After a median follow-up duration of 3.65 years, statins treatment was not associated with the risk of all bleeding (RR=1.03, 95% CI 0.93-1.15). Furthermore, in 26 studies comprising 144,177 participants, after a median follow-up duration of 3.95 years, statins treatment was not associated with the risk of ICH (RR=1.05, 95% CI 0.84-1.31). Although in the subgroup analysis with patients with prior stroke, statins treatment showed an increased risk of ICH (RR=1.47, 95% CI 1.07-2.01), sensitivity analysis showed that the result was unstable, which may be mainly driven by the SPARCL study. Statins therapy is not associated with the risk of all bleeding and ICH. Although a mildly increased risk of ICH in patients with prior stroke is observed, which may be caused by chance finding and warrant further documentation.

Antiplatelet Medications and Intracranial Hemorrhage in Patients with Primary Brain Tumors

Background: Intracranial hemorrhage (ICH) frequently complicates the clinical course of patients with brain tumors. These bleeding events carry significant morbidity and portend poor survival outcomes. The frequent need to prescribe antiplatelet medications, including aspirin and P2Y12 inhibitors, further complicates the risk of hemorrhage in this patient population with concurrent cardiovascular or cerebrovascular indications. The impact of these agents on rates of ICH in the general population has previously been studied and remains equivocal. Whether antiplatelet medications increase the risk of ICH in primary brain tumors remains undefined, and there is limited evidence to guide their use in this setting. Aims: We investigated whether patients with primary brain tumors receiving antiplatelet medications had an increased risk of ICH compared to a matched cohort. Methods: This study was a retrospective matched cohort study of patients with diagnosis of primary brain tumor treated at our center between 2010-2021. Patients with metastatic brain disease were excluded. Patients treated with antiplatelet medications (aspirin and P2Y12 inhibitors) were matched with patients not receiving these agents. Matching was performed using a scoring algorithm that ranked controls according to cancer type, exposure to anticoagulation, age, sex, and year of diagnosis. The primary end point of the study was the cumulative incidence of ICH at 1 year after tumor diagnosis. Radiologic images of bleeding events were assessed by a neuroradiologist blinded to the study cohort allocation. ICH was defined as trace (< 1 cm3), measurable (1 - 10 cm3), or major (symptomatic or > 10 cm3), with bleed volumes defined by the ½ ABC method. Results: The study population included 398 patients with primary brain tumors. 134 patients were exposed to antiplatelet medications. Of these 134 patients, 123 were exposed to aspirin alone, 10 were exposed to dual antiplatelet therapy (aspirin and P2Y12 inhibitor), and 1 received P2Y12 inhibitor alone. The most common malignancy in the study cohort was glioma (78%). The cumulative incidence of ICH at 1 year was 10.8% (95% CI, 5.2 - 16.3) in those receiving antiplatelet agents compared with 13.6% (95% CI, 9.0 - 18.2) in the control population (P = 0.48, Gray test). The cumulative incidence of major ICH at 1 year was 7.2% (95% CI, 2.6 - 11.7) in those receiving antiplatelet agents compared to 4.8% (95% CI, 2.0 - 7.5) among controls (P = 0.48, Gray test) (Figure 1). The distribution of ICH volume size was similar in the 2 groups (Table 1). The combined use of antiplatelet medication with anticoagulation did not increase the risk of total ICH compared to patients that did not receive either (HR 1.53, 95% CI 0.74 - 3.17) but did increase the risk of major ICH compared with patients that did not receive either (HR 3.41, 95% CI 1.04 - 11.19, P = 0.043). Median overall survival in patients exposed to antiplatelet medications was 28.3 months (95% CI, 19.6 - 47.9) compared to 20.8 months in those not exposed (95% CI, 16.6 - 30.6, P = 0.09). Conclusions: In patients with primary brain tumors, administration of antiplatelet medications was not associated with an increased incidence of ICH. However, there was an increased risk of major ICH for patients exposed to both antiplatelet medication and anticoagulation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Safety and efficacy of adjunct tirofiban treatment following mechanical thrombectomy for acute ischemic stroke patients with large vessel occlusion (LVO) resulting in successful reperfusion.

Tirofiban administration after mechanical thrombectomy (MT) remains controversial. This study aimed to investigate the efficacy and safety of adjunct tirofiban treatment following MT for acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) that resulted in successful reperfusion on digital subtraction angiography (DSA). This retrospective study was conducted in Zhengzhou University University People's Hospital, an advanced stroke center in China. Consecutive patients with AIS who underwent endovascular therapy (EVT) were enrolled from June 2018 to January 2022. The safety endpoints were symptomatic intracerebral hemorrhage (sICH), total intracranial hemorrhage (ICH), and 3-month mortality. The efficacy endpoints were 3-month modified Rankin scale (mRS) score and 24-h neurological improvement. A total of 145 consecutive patients with AIS who underwent MT were analyzed, of whom 51 (35.2%) patients were in the tirofiban group. There were 30 (20.7%) patients with sICH, 50 (34.5%) patients suffered from ICH within 24-h post-MT, and 47 (32.4%) dead at 3-month. Besides, 31 (21.4%) patients achieved excellent clinical outcomes (mRS, 0-1), and 24-h neurological improvement was found in 29 (20.0%) patients. No statistically significant differences were found in safety outcomes on sICH, total ICH, and 3-month mortality, as well as efficacy outcomes on 3-month mRS scores (0-1) and 24-h neurological improvement between the two groups (P > 0.05 for all). Additionally, tirofiban was associated with 3-month mRS scores of 0-2 (adjusted odds ratio (OR), 3.75; 95% confidence interval (CI), 1.41-10.02, P = 0.008). Adjunct tirofiban treatment following MT for AIS patients with LVO that resulted in successful reperfusion on DSA was not correlated with the increased risk of safety endpoints on sICH, ICH, and 3-month mortality, and it may be associated with a lower 3-month mRS score.

Abstract WP9: Iv Tpa For Acute Ischemic Stroke In The Setting Of Intracranial Tumor: A Systematic Review

Objective: Intracranial tumor is considered a contraindication to IV tPA for presumed acute ischemic stroke (AIS), though evidence differentiating rate of intracranial hemorrhage (ICH) in benign versus malignant neoplasm is lacking. A systematic review of published cases of standard-dose IV tPA for AIS within 4.5 hours of symptom onset and intracranial tumor was performed. Methods: PubMed, Embase, and Cochrane were used to identify articles for inclusion. Case reports, letters to the editor, conference proceedings, cohort studies, case series, literature reviews, and case-control studies that included patients given standard dose IV tPA for presumed AIS within 4.5 hours of symptom onset, who were found to have an intracranial tumor, were included. The primary outcome measure was the rate of ICH. Results: Twenty-three studies met inclusion criteria, involving 495 patient cases. One of the included case-control studies presented data only in the form of an odds ratio (OR), with OR 0.72 (p=0.16) for risk of ICH out of 297 benign brain tumors as compared to controls. They found an OR for ICH of 2.33 (p value &lt;0.001) in 119 malignant brain tumors as compared to controls. The remaining 22 sources included a total of 79 cases, 49 of which were classified as benign, 16 malignant, and 14 “not otherwise specified.” Of these 79 cases, ICH occurred in 4, one of which was an asymptomatic parenchymal hematoma (5.1% total ICH, 3.8% symptomatic ICH). ICH only occurred in cases of malignant or metastatic intracranial tumors. There were no reports of ICH following IV tPA in patients with a benign intracranial tumor. Meta-analysis could not be performed due to substantial heterogeneity in study design and reported patient data in included sources. Conclusion: There were no reports of ICH in the setting of benign intracranial tumor, and the reported rate of ICH with standard-dose IV tPA in the setting of any brain tumor appears similar to the general AIS population. There is significant heterogeneity of sources and risk of selection bias with the included studies, such that these findings are not confirmatory. Further research is needed to assess the rate of ICH with IV tPA for AIS in the setting of brain tumor.

Impact of Antithrombotic Agents on Radiological Lesion Progression in Acute Traumatic Brain Injury: A CENTER-TBI Propensity-Matched Cohort Analysis.

An increasing number of elderly patients are being affected by traumatic brain injury (TBI) and a significant proportion are on pre-hospital antithrombotic therapy for cardio- or cerebrovascular indications. We have quantified the impact of antiplatelet/anticoagulant (APAC) agents on radiological lesion progression in acute TBI, using a novel, semi-automated approach to volumetric lesion measurement, and explored the impact of use on clinical outcomes in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We used a 1:1 propensity-matched cohort design, matching controls to APAC users based on demographics, baseline clinical status, pre-injury comorbidities, and injury severity. Subjects were selected from a pool of patients enrolled in CENTER-TBI with computed tomography (CT) scan at admission and repeated within 7 days of injury. We calculated absolute changes in volume of intraparenchymal, extra-axial, intraventricular, and total intracranial hemorrhage (ICH) between scans, and compared volume of hemorrhagic progression, proportion of patients with significant degree of progression (>25% of initial volume), proportion with new ICH on follow-up CT, as well as clinical course and outcomes. A total of 316 patients were included (158 APAC users; 158 controls). The mean volume of progression was significantly higher in the APAC group for extra-axial (3.1 vs. 1.3 mL, p = 0.01), but not intraparenchymal (3.8 vs. 4.6 mL, p = 0.65), intraventricular (0.2 vs. 0.0 mL, p = 0.79), or total intracranial hemorrhage (ICH; 7.0 vs. 6.0 mL, p = 0.08). More patients had significant hemorrhage growth (54.1 vs. 37.0%, p = 0.003) and delayed ICH (4 of 18 vs. none; p = 0.04) in the APAC group compared with controls, but this was not associated with differences in length of stay (LOS), rates of neurosurgical intervention, mortality or Glasgow Outcome Scale Extended (GOS-E) score at 6 months. Pre-injury use of antithrombotic agents was associated with greater expansion of extra-axial lesions, higher rates of significant hemorrhagic progression, and higher risk of delayed traumatic ICH, but this was not associated with worse clinical course or functional outcomes.

The Second Strategic Reperfusion Early After Myocardial Infarction (STREAM-2) study optimizing pharmacoinvasive reperfusion strategy in older ST-elevation myocardial infarction patients

The STREAM study demonstrated that a pharmaco-invasive strategy was at least as effective as primary PCI (pPCI) in patients presenting early with ST-elevation myocardial infarction (STEMI). The current trial is a response to the finding that reduced intracranial hemorrhage (ICH) in patients ≥75 years occurred after halving the dose of tenecteplase. Additionally, a subsequent analysis of full dose tenecteplase or alteplase in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT) trials demonstrated a steep increase in bleeding events beginning around the age of 60 years. STREAM-2 will compare the efficacy and safety of a novel pharmaco-invasive strategy as compared to routine pPCI in STEMI patients ≥60 years presenting within 3 hours from symptom onset. In the pharmaco-invasive arm patients will receive half-dose tenecteplase, as soon as possible before transport to a PCI center. In the pPCI arm, patients will be treated according to optimal standard of care defined by local practice. The key criteria for efficacy will be the number of patients achieving ≥50% ST-segment resolution before and after PCI in lead with maximal ST elevation at baseline and the clinical endpoints of death, congestive heart failure, shock or re-infarction, rescue PCI and aborted myocardial infarction, both singularly and as a composite at 30 days. Key safety criteria are total stroke, ICH and major non-intracranial bleeds. Approximately 600 patients will be randomized (400 to pharmaco-invasive treatment and 200 to pPCI). An interim analysis is planned after 300 patients are enrolled to consider adapting the trial to include a larger sample size aimed at undertaking a formal confirmatory trial. The study will provide new insights aimed at establishing an effective and safer pharmaco-invasive treatment for the growing population of older STEMI patients who cannot undergo timely pPCI.

Safety and Efficacy of Heparinization During Mechanical Thrombectomy in Acute Ischemic Stroke.

Background: The benefits of heparization during mechanical thrombectomy (MT) with newer generation thrombectomy devices, and if it is counterbalanced by the increased risk of intracranial hemorrhage (ICH) remain unknown.Methods: We included eligible patients who underwent MT from the ANGEL registry study (2015-2017) in China. Subjects in the current analysis were dichotomized into two groups according to whether adequate heparinization during MT was performed. In the heparinization group, unfractionated heparin was infused at 50–100 IU/Kg at first and additional 1,000 IU at intervals of an hour during the operation. Safety outcomes (symptomatic intracerebral hemorrhage [sICH], ICH and distal embolization) and efficacy outcomes (artery recanalization and functional outcomes at 3-month follow-up) were compared between groups.Results: We included 619 patients from the entire cohort of 917 patients. The average age of them was 63.9 ± 13.7 years, 269 (43.5%) were treated with heparinization during MT. Heparinization during MT didn't significantly influence recanalization rates, total ICH and long-term mortality (adjusted p > 0.05 for all). But sICH and distal embolization occurred more frequently (9.3 vs. 5.1%, adjusted p = 0.02; 7.1 vs. 3.1%, adjusted p = 0.04, respectively), while functional independence appeared less likely (39.8 vs. 47.4%, adjusted p = 0.01) in heparinization group than that in non-heparinization group. Multivariable logistic regression analyses showed that heparinization during MT was an independent predictor for sICH (Odds ratio 2.36 [1.19–4.67], p = 0.01) in addition to cardio-embolism stroke and posterior circulation stroke (PCS), and an independent predictor for poor outcome (Odds ratio 1.79 [1.23–2.59], p < 0.01) besides age, bridging intravenous thrombolysis, admission NIHSS, drinking and PCS.Conclusion: Heparinization during MT may be associated with increased risk of safety outcomes over sICH and distal embolization, as well as efficacy outcomes over long-term poor outcome. Further randomized controlled trials are needed.

Time to Reset the Definition of Successful Revascularization in Endovascular Treatment of Acute Ischemic Stroke

Background: A 2013 consensus statement recommended the use of the modified Treatment In Cerebral Ischemia (mTICI) scale to evaluate angiographic revascularization after endovascular treatment (EVT) of acute ischemic stroke due to its higher inter-rater agreement and capacity of clinical outcome prediction. The current definition of successful revascularization includes the achievement of grades mTICI 2b or 3. However, mTICI 2b grade encompasses a large heterogeneity of revascularization states, and prior studies suggested that the magnitude of benefit derived from mTICI 2b and mTICI 3 does not seem to be equivalent. In a way to restrain the referred heterogeneity, Goyal et al. [J Neurointerv Surg 2014; 6: 83–86] proposed a revised mTICI scale that includes a 2c grade (rTICI). Methods: Retrospective analysis of prospectively collected data from consecutive cases of EVT for anterior circulation large-vessel occlusion, performed between January 2015 and July 2017. Patients with mTICI 2b or 3 grades were reclassified according to the rTICI scale, and the outcomes between the 3 revascularization grades (rTICI 2b, 2c, 3) compared. Results: Our study population of 226 patients (64 rTICI 2b, 30 rTICI 2c, 132 rTICI 3) has a mean age of 71 years, 48.2% males, median baseline NIHSS of 16 (13–19) and ASPECTS of 8 (7–9). The 3 revascularization grades are represented by homogeneous populations. Logistic regression analysis showed statistically significant higher rates of functional independence at 3 months (65.9 vs. 50.0%; adjusted OR 0.39, 95% CI 0.18–0.86), with lower rates of mortality (8.3 vs. 15.6%; adjusted OR 3.54, 95% CI 1.14–10.97) and intracranial hemorrhage (ICH) in rTICI 3 than 2b groups. When comparing rTICI 3 with 2c groups, there were only statistically significant differences in the total ICH rate (8.3 vs. 26.7%; adjusted OR 7.08, 95% CI 1.80–27.82) but not in symptomatic ICH. Conclusions: These results corroborate the scarce prior findings suggesting that patients with rTICI 2c grade should be reported separately, since they have similar outcomes to rTICI 3, and better than rTICI 2b patients. Therefore, we suggest resetting the angiographic revascularization endpoint to perfect revascularization (rTICI 2c or 3 grades), a target that neurointerventionalists should strive to achieve.

Abstract W P313: Risk of Rebleed with Resumption of Anticoagulation after Intracranial Hemorrhage

Introduction: Rebleed after resumption of anticoagulation following intracranial hemorrhage (ICH) remains a substantial concern, but little data is available describing the occurrence of such events. Methods: Prospectively collected data from 2008-2011 was reviewed in patients with intraparencymal (IPH), subdural (SDH), and subarachnoid (SAH) hemorrhage. Patients with anticoagulant use prior to ictus were identified, as were patients started on full anticoagulation during hospitalization. In hospital rates of ischemic events, major and minor hemorrhages were collected. Univariate analyses were performed using either Fisher’s exact or Mann-Whitney U tests. Results: 387 total ICH patients were identified, including 132 (34.1%) SAH, 134 (34.6%) SDH, and 121 (31.3%) IPH. At time of ictus, 67 (17.3%) were anticoagulated and underwent reversal of coagulopathy. Of these 67 patients, ischemic complications including myocardial infarction (MI), pulmonary embolism (PE), and deep vein thrombosis (DVT) occurred in 8 (11.9%) during hospitalization. 6 of 67 (9.0%) patients resumed full anticoagulation at a median of 14.5 days from ictus. 14 additional patients were started on full anticoagulation de novo at a median of 12 days from ictus. Significant indications for anticoagulation after ICH included: 4 (20%) history of valvular heart disease, 7 (35%) DVT, 1 (5%) PE, 7 (35%) arrhythmia, and 1 (5%) coronary artery disease. Of the 20 patients fully anticoagulated after ICH, 2 (10%) experienced a major hemorrhagic complication. 1 new ICH occurred 36 days from ictus on the day anticoagulation was restarted, and 1 SDH expansion occurred 56 days from ictus and 47 days from resuming anticoagulation. 1 patient experienced a minor hemorrhagic complication (retroperitoneal hematoma). Conclusions: Ischemic complications occurred in 11.9% of ICH patients who underwent coagulopathy reversal. It remains unclear if coagulopathy reversal or delay to resuming anticoagulation is the cause of ischemic events. Initiation of anticoagulation after a median of 14 days from ictus was associated with major hemorrhage in 10% of patients. Reversal of anticoagulation and initiation of anticoagulation after a median of 14 days is associated with an acceptable risk profile.

The Relationship Between Subarachnoid Hemorrhage Volume and Development of Cerebral Vasospasm

ObjectiveThe objective of this study is to verify the relationship between subarachnoid hemorrhage (SAH) volume (not Fisher grade) and development of cerebral vasospasm prospectively.MethodsPatients who visited our hospital with a diffuse or localized thick subarachnoid blood clot seen on computed tomography (CT), taken within 48 hours after SAH and the aneurysm was confirmed by CT Angiogram (CTA) from March 2010 to July 2011 were enrolled in this study. CTA was checked at least twice after admission. Angiographic vasospasm (AVS) on CTA was defined as irregularity or narrowing of intracranial vessels on follow up CTA compared with initial CTA. Total intracranial hemorrhage (ICH) volume (subdural, SAH, intracerebral and intraventricular) was calculated and SAH volume (all supratentorial and infratentorial cisterns) was also calculated using the MIPAV software package.ResultsA total of 55 patients were included in our study. Thirty six patients did not show AVS on CTA or clinical deterioration (non vasospasm group: NVS). AVS without ischemic neurologic symptoms was observed in four patients and development of symptomatic vasospasm (SVS), defined as AVS with ischemic symptoms, was observed in 15 patients. SAH volume in SVS patients was statistically larger than that in NVS patients (p < 0.05). Total ICH volume in SVS patients was larger than that in NVS patients. However, the difference was not statistically significant.ConclusionResults of this study indicate an association of development of vasospasm with the SAH volume, not intracranial hemorrhage.

Microcatheter contrast injections during intra-arterial thrombolysis increase intracranial hemorrhage risk

Background and purposeCombined analysis of the Interventional Management of Stroke I and II trials demonstrated a significant association between microcatheter contrast injections and both intracranial hemorrhage (ICH) and contrast extravasation...