Hemorrhagic Transformation Patients Research Articles

Predictors of hemorrhagic transformation in patients of first ever acute ischemic stroke receiving recombinant tissue plasminogen activator (rTPA)

Abstract Background Hemorrhagic transformation (HT) represents a serious complication of acute ischemic stroke (AIS). Aim To detect predictive factors linked to HT among patients having a first-ever AIS who received recombinant tissue plasminogen activator (rTPA), for better preselection of patients eligible for thrombolytic therapy. Patients and methods This research took place at the Neuropsychiatry Department and Centre of Psychiatry, Neurology, and Neurosurgery, Tanta University Hospitals over 12 months. The total number of patients included was 460, with 115 who received rTPA and 345 who did not receive rTPA. All participants underwent a comprehensive medical history, clinical and neurological assessments, radiological evaluation (ASPECT score), cardiac investigation, and were followed-up for two weeks to detect any HT. Results Patients with HT represented 21.7% of all rTPA patients, with symptomatic intracranial hemorrhage representing 6.9%, while non-rTPA patients with HT represented 13.9% and symptomatic intracranial hemorrhage represented 4.3%. HT patients in the rTPA group had significantly higher rates of smoking, respiratory rate, and lower platelet count, low density lipoprotein and cholesterol levels, while HT patients in the non-rTPA group exhibited significantly higher blood pressure, random blood sugar, as well as lower ASPECT scores. Conclusion There was an association between HT and five predictors (higher smoking rate, higher respiratory rate, lower platelet count, and lower low density lipoprotein and cholesterol levels) in first ever acute ischemic stroke patients receiving rTPA. In patients who did not receive rTPA, HT was associated with lower ASPECT scores, higher blood pressure, and random blood sugar.

The differences of fibrinogen levels in various types of hemorrhagic transformations.

Hemorrhagic transformation (HT) is a serious complication that can occur spontaneously after an acute ischemic stroke (AIS) or after a thrombolytic/mechanical thrombectomy. Our study aims to explore the potential correlations between fibrinogen levels and the occurrence of spontaneous HT (sHT) and HT after mechanical thrombectomy (tHT). A total of 423 consecutive AIS patients diagnosed HT who did not undergone thrombolysis and 423 age- and sex-matched patients without HT (non-HT) were enrolled. Fibrinogen levels were measured within 24 h of admission after stroke. The cohorts were trisected according to fibrinogen levels. The HT were further categorized into hemorrhagic infarction (HI) or parenchymal hematoma (PH) based on their imaging characteristics. In sHT cohort, fibrinogen levels were higher in HT patients than non-HT patients (p < 0.001 versus p = 0.002). High fibrinogen levels were associated with the severity of HT. HT patients without atrial fibrillation (AF) had higher levels of fibrinogen compared to non-HT (median 3.805 vs. 3.160, p < 0.001). This relationship did not differ among AF patients. In tHT cohort, fibrinogen levels were lower in HT patients than non-HT patients (p = 0.002). Lower fibrinogen levels were associated with the severity of HT (p = 0.004). The highest trisection of fibrinogen both in two cohorts were associated with HT [sHT cohort: OR = 2.515 (1.339-4.725), p = 0.016; that cohort: OR = 0.238 (0.108-0.523), p = 0.003]. Our study suggests that lower fibrinogen level in sHT without AF and higher fibrinogen level in tHT are associated with more severe HT.

The combination model of serum occludin and clinical risk factors improved the efficacy for predicting hemorrhagic transformation in stroke patients with recanalization

Backgroundand Purpose: Hemorrhagic transformation (HT) is one of the severe complications in acute ischemic stroke, especially for the patients who undergo recanalization treatment. It is crucial to screen patients who have high risk of HT before recanalization. However, current prediction models based on clinical factors are not ideal for clinical practice. Serum occludin, a biomarker for cerebral ischemia-induced blood-brain barrier disruption, has potential for predicting HT. This study was to investigate whether the combination of serum occludin and clinical risk factors improved the efficacy of predicting HT. MethodsThis was a single-center prospective observational study. Baseline clinical data and blood samples of recanalization patients were collected upon admission to our hospital. The level of serum occludin was measured using enzyme-linked immunosorbent assay. The diagnosis of HT was confirmed by CT scans within 36 h post recanalization. ResultsA total of 324 patients with recanalization were enrolled and 68 patients presented HT occurrence. HT patients had the higher level of baseline occludin than patients without HT (p < 0.001). Multivariate regression analysis showed that serum occludin level, Alberta Stroke Program Early CT Scores and endovascular therapy were independent risk factors (p < 0.05) for HT after adjusting potential confounders. The combination of serum occludin and clinical risk factors significantly improved the accuracy of predicting HT [area under the curve (AUC, 0.821 vs 0.701, p < 0.001), and net reclassification improvement (31.1 %), integrated discrimination improvement (21.5 %), p < 0.001] compared to a model employing only clinical risk factors. The modified AUC (0.806) of combined model based on 10-fold-cross-validation was still higher than clinical risk model (0.701). ConclusionThe combination of serum occludin and clinical risk factors significantly improved the prediction efficacy for HT, providing a novel potential prediction model to screen for patients with high risk of HT before recanalization in acute ischemic stroke.

Prognostic Burden of Hemorrhagic Transformation in Acute Ischemic Stroke: A Brief Report from the Real Life

Introduction: Hemorrhagic Transformation (HT) represents one of the main complications of acute ischemic stroke, affecting its management and prognosis. Few data exists on prognosis of HT in the real world. Aim of this study was to evaluate the prognostic impact of HT in a real world cohort of patients hospitalized for acute ischemic stroke. Methods: We retrospectively analyzed the clinical data of patients with acute ischemic stroke consecutively admitted to our Stroke Unit. Patients with HT were compared with those without HT. Modified Rankin Scale (mRS) at hospital discharge and at 90 days were the study outcomes. Poor prognosis was defined as mRS≥4. A multivariate logistic regression analysis was performed to identify independent predictors of outcomes. Results: The study population consisted of 564 patients with mean age 77.5±11.8 years. Fifty-two patients (9.2%) showed HT on brain CT. Length of hospitalization, in-hospital mortality, median mRS at discharge, percentage of patients with mRS≥4 at discharge, percentage of HT patients discharged without secondary antiplatelet or anticoagulant prophylaxis and median 90- day mRS were significantly higher in patients with HT than in those without. The presence of HT was predictive of mRS≥4 at discharge and at 90 days (AUC 0.720 and 0.776, respectively). The presence of HT was an independent predictor of poor outcome, increasing the risk by about four times both at discharge (OR 3.64, 95% 1.46-9.06) and at 90 days (OR 4.26, 95% 1.07-16.88). Conclusions: HT is associated with a poor outcome in terms of mortality and severe residual disability both in the acute phase and at 90 days.

Timing of Antithrombotic Secondary Prevention in Patients with Intracranial Hemorrhage after Stroke Thrombolysis and Thrombectomy.

In patients with acute ischemic stroke, hemorrhagic transformation (HT) of infarcted tissue frequently occurs after reperfusion treatment. We aimed to assess whether HT and its severity influences the start of secondary prevention therapy and increases the risk of stroke recurrence. In this retrospective dual-center study, we recruited ischemic stroke patients treated with thrombolysis, thrombectomy or both. Our primary outcome was the time between revascularization and the start of any secondary prevention therapy. The secondary outcome was ischemic stroke recurrence within three months. We compared patients with vs. without HT and no (n = 653), minor (n = 158) and major (n = 51) HT patients using propensity score matching. The delay in the start of antithrombotics or anticoagulants was median 24 h in no HT, 26 h in minor HT and 39 h in major HT. No and minor HT patients had similar rates of any stroke recurrence (3.4% (all ischemic) vs. 2.5% (1.6% ischemic plus 0.9% hemorrhagic)). Major HT patients had a higher stroke recurrence at 7.8% (3.9% ischemic, 3.9% hemorrhagic), but this difference did not reach significance. A total of 22% of major HT patients did not start any antithrombotic treatment during the three-month follow-up. In conclusion, the presence of HT influences the timing of secondary prevention in ischemic stroke patients undergoing reperfusion treatments. Minor HT did not delay the start of antithrombotics or anticoagulants compared to no HT, with no significant difference in safety outcomes. Major HT patients remain a clinical challenge with both a delayed or lacking start of treatment. In this group, we did not see a higher rate of ischemic recurrence; however, this may have been censored by elevated early mortality. While not reaching statistical significance, hemorrhagic recurrence was somewhat more common in this group, warranting further study using larger datasets.

In-Hospital Aspirin Dose as a Risk Factor for Hemorrhagic Transformation in Patients Not Treated With Thrombolysis.

Aspirin is widely used as secondary prophylaxis for acute ischemic stroke. However, its influence on the risk of spontaneous hemorrhagic transformation (HT) is still unclear. Predictive scores of HT have been proposed. We hypothesized that an increased aspirin dose might be harmful in patients at a high risk of HT. This study aimed to analyze the relationship between in-hospital daily aspirin dose (IAD) and HT in patients with acute ischemic stroke. We conducted a retrospective cohort study of patients admitted to our comprehensive stroke center between 2015 and 2017. The attending team defined IAD. All included patients underwent either computed tomography or magnetic resonance imaging within 7 days of admission. The risk of HT was assessed using the predictive score of HT in patients not undergoing reperfusion therapies. Regression models were used to evaluate the correlations between HT and IAD. A total of 986 patients were included in the final analysis. The prevalence of HT was 19.2%, and parenchymatous hematomas type-2 (PH-2) represented 10% (n=19) of these cases. IAD was not associated with HT ( P =0.09) or PH-2 ( P =0.06) among all patients. However, in patients at a higher risk for HT (patients not undergoing reperfusion therapies ≥3), IAD was associated with PH-2 (odds ratio 1.01,95% CI 1.001-1.023, P =0.03) in an adjusted analysis. Taking 200 versus 300mg aspirin was protective against PH-2 (odds ratio 0.102, 95% CI 0.018-0.563, P =0.009). An increased in-hospital aspirin dose is associated with intracerebral hematoma in patients at a high risk of HT. Stratifying the risk of HT may lead to individualized daily aspirin dose choices. However, clinical trials on this topic are required.

Endothelial NO synthase 786T/T polymorphism increases hemorrhagic transformation after endovascular thrombectomy

Background and purposeThis study examined whether the 786 NOS3 polymorphism is associated with the risk of hemorrhagic transformation (HT) in stroke patients with anterior large vessel occlusion (ALVO) treated using endovascular thrombectomy (EVT). MethodsWe performed an observational cohort study that included 118 patients with ALVO who underwent EVT. HT was assessed in follow-up CT and MRI. HT and non-HT patients were compared in terms of the 786 NOS3 polymorphism, flow mediated dilation (FMD) values within 3 days after the stroke, and collateral status based on three grading scales. Demographics, vascular risk factors, additional radiological data including ASPECT score, thrombus length and infarct size, and EVT procedure and outcome variables were also included. ResultsRadiological HT occurred in 55 (46.6%) patients and the 786T/T NOS3 polymorphism was associated with HT (unadjusted OR of 2.33, 95%CI: 1.05–5.20, adjusted OR of 3.14, 95%CI: 1.16–8.54). Collateral status and systemic endothelial function assessed by FMD were not mediators of this relationship as no differences were seen in the median FMD percentage values or collateral status between NOS3 genotypes. ConclusionsOur results suggest that genetic variations affecting the NO pathway, such as the 786 NOS3 polymorphism, may contribute to individual variability in the occurrence of HT and these results support involvement of this pathway in the pathogenesis of ischemia-reperfusion injury after EVT.

Weak lesion feature extraction by dual-branch separation and enhancement network for safe hemorrhagic transformation prediction.

Hemorrhagic transformation (HT) is regarded as a safety endpoint of arterial ischemic stroke acute treatment and secondary prevention trials (Hutchinson and Beslow, 2019). Accurate HT prediction dramatically reduces the death rate from misdiagnosis. At present, HT predictions almost all rely on contrast images with perfusion agents, which is time-consuming and labor-intensive, causing secondary brain damage and high cost. Almost all machine learning algorithms cannot use non-contrast CT for HT prediction because of huge challenges. In this study, a Dual-branch Separation and Enhancement Network (DBSE-Net) is proposed for weak feature extraction and safe HT prediction without perfusion agents. DBSE-Net innovatively uses a dual-branch separation and fusion mechanism to achieve weak feature adaptive extraction. In the DBSE-Net's encoder submodules, Brain Compression Assessment Branch (BCAB) and Infarct Assessment Branch (IAB) are proposed to apply lightweight encoding structures with different receptive fields, which are adapted to the lesion area's characteristics. With the help of DBSE-Net's keyframe selection algorithm and area guidance knowledge, DBSE-Net removes redundant information and clearly describes the severity of lesions. In summary, DBSE-Net integrates global and local features to obtain multi-scale and multi-category brain status information, enhancing the weak features of non-contrast CT and realizes accurate HT prediction. Experimental Result: Among all 144 intracranial stroke patients diagnosed by doctors as having no HT risk, DBSE-Net identified 73 high-risk HT patients (88 HT cases in total). The result illustrates that DBSE-Net helps doctors secondary diagnose the HT risk of intracranial stroke patients and becomes a potential tool to prevent doctors from false HT risk diagnosis.

Hemorrhagic Transformation in Acute Ischemic Stroke: A Quantitative Systematic Review.

The prevalence and risk factors of hemorrhagic transformation (HT) after acute ischemic stroke HT have not been adequately delineated. We performed a systematic review and meta-analysis to identify English-language prospective observational MEDLINE and EMBASE-listed reports of acute ischemic stroke with HT published from 1985–2017. Studies that used the ECASS-2 definitions of hemorrhagic transformation subtypes, hemorrhagic infarction (HI), and parenchymal hematoma (PH) were included. Patients treated with intravenous thrombolysis with tissue plasminogen activator (IV-tPA) were compared with those who did not receive thrombolysis. A total of 65 studies with 17,259 patients met inclusion criteria. Overall, HT prevalence was 27%; 32% in patients receiving IV-tPA vs. 20% in those without. Overall PH prevalence was 9%; 12% in IV-tPA treated patients vs. 5% in those without. HT was associated with a history of atrial fibrillation (OR 2.94) and use of anticoagulants (OR 2.47). HT patients had higher NIHSS (Hedge’s-G 0.96) and larger infarct volume (diffusion-weighted MRI, Hedge’s-G 0.8). In IV-tPA treated patients, PH correlated with antiplatelet (OR 3) and statin treatment (OR 4). HT (OR 3) and PH (OR 8) were associated with a poor outcome at 90-day (mRS 5–6). Hemorrhagic transformation is a frequent complication of acute ischemic stroke and is associated with poor outcome. Recognition of risk factors for HT and PH may reduce their incidence and severity.

GAS6/Axl Signaling Modulates Blood-Brain Barrier Function Following Intravenous Thrombolysis in Acute Ischemic Stroke.

Background and PurposeRecent studies have shown that several proteins, including Axl, are related to hemorrhagic transformation (HT) following intravenous thrombolysis by affecting blood-brain barrier (BBB) function. However, the effects of these proteins on BBB function have been studied primarily in animal models. In this study, we aimed to identify serum protein markers that predict HT following intravenous thrombolysis in patients with acute ischemic stroke (AIS) and verify whether these serum proteins regulate BBB function and HT in animal stroke models.MethodsFirst, 118 AIS patients were enrolled in this study, including 52 HT patients and 66 non-HT patients. In Step 1, baseline serum levels of Axl, angiopoietin-like 4, C-reactive protein, ferritin, hypoxia-inducible factor-1 alpha, HTRA2, Lipocalin2, matrix metallopeptidase 9, platelet-derived growth factor-BB, and tumor necrosis factor alpha were measured using a quantitative cytokine chip. Next, sequence mutations and variations in genes encoding the differentially expressed proteins identified in Step 1 and subsequent function-related proteins were detected. Finally, we verified whether manipulation of differentially expressed proteins affected BBB function and HT in a hyperglycemia-induced rat stroke model.ResultsSerum Axl levels were significantly lower in the HT group than in the non-HT group; none of the other protein markers differed significantly between the two groups. Genetic testing revealed that sequence variations of GAS6 (the gene encoding the Axl ligand)-derived long non-coding RNA, GAS6-AS1, were significantly correlated with an increased risk of HT after intravenous thrombolysis. In animal studies, administration of recombinant GAS6 significantly reduced brain infarction and neurological deficits and attenuated BBB disruption and HT.ConclusionsLower serum Axl levels, which may result from sequence variations in GAS6-AS1, are correlated with an increased risk of HT after intravenous thrombolysis in stroke patients. Activation of the Axl signaling pathway by the GAS6 protein may serve as a therapeutic strategy to reduce HT in AIS patients.

Serum Occludin Level Combined With NIHSS Score Predicts Hemorrhage Transformation in Ischemic Stroke Patients With Reperfusion.

Hemorrhagic transformation (HT) is a severe complication following acute ischemic stroke, particularly with reperfusion interventions, leading to poor prognosis. Serum occludin level is related with blood brain barrier disruption, and the National Institute of Health stroke scale (NIHSS) score reflects stroke severity. We investigated whether the two covariates are independently associated with HT and their combination can improve the accuracy of HT prediction in ischemic stroke patients with reperfusion therapy. Seventy-six patients were screened from the established database of acute ischemic stroke in our previous study, which contains all clinical information, including serum occludin levels, baseline NIHSS score, and hemorrhagic events. Multivariate logistic regression analysis showed that serum occludin level (OR = 4.969, 95% CI: 2.069–11.935, p < 0.001) and baseline NIHSS score (OR = 1.293, 95% CI 1.079–1.550, p = 0.005) were independent risk factors of HT after adjusting for potential confounders. Compared with non-HT patients, HT patients had higher baseline NIHSS score [12 (10.5–18.0) versus 6 (4–12), p = 0.003] and serum occludin level (5.47 ± 1.25 versus 3.81 ± 1.19, p < 0.001). Moreover, receiver operating characteristic curve based on leave-one-out cross-validation showed that the combination of serum occludin level and NIHSS score significantly improved the accuracy of predicting HT (0.919, 95% CI 0.857–0.982, p < 0.001). These findings suggest that the combination of two methods may provide a better tool for HT prediction in acute ischemic stroke patients with reperfusion therapy.

Serum homocysteine level is an independent predictor for hemorrhagic transformation within 24 h of intravenous thrombolysis in acute ischemic stroke

The study aimed to investigate the role of serum homocysteine in hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 h of intravenous (IV) recombinanttissueplasminogenactivator(rt-PA) in acute ischemic stroke (AIS) patients. 236 consecutive AIS patients (169 men, median 65 years old) who underwent to IV rt-PA within 4.5 h of symptom onset were retrospectively recruited and analyzed. The serum homocysteine levels ranged from 4.45 to 67.71 (median 12.05) μmol/L. HT was observed in 28 (11.9%) patients, including 7 (3.0%) sICH patients within 24 h of IV rt-PA. Multiple parameters were compared between HT and non-HT patients as well as sICH and non-sICH patients. The serum homocysteine levels were higher in patients with HT than in those without HT (13.00 vs. 11.70 μmol/L, P = 0.025) and an independent association between serum homocysteine level and HT within 24 h of IV rt-PA was identified via multivariable logistic regression analysis (odds ratio [OR] = 1.103, 95% confidence interval [CI] = 1.021–1.191, P = 0.013). Moreover, serum homocysteine levels were also significantly higher in patients with sICH than in those without sICH (15.19 vs. 11.73 μmol/L, P = 0.005).Our study suggests that serum homocysteine level is an independent predictor for HT within 24 h of IV rt-PA in AIS patients.

Incidence, risk factors, clinical presentation, and outcomes of hemorrhagic transformation in patients with ischemic stroke admitted to a tertiary hospital in Kingdom of Saudi Arabia.

Objectives:To describe the incidence rate, clinical presentation, relevant risk factors, and outcome of hemorrhagic transformation (HT) among ischemic stroke patients.Methods:This retrospective study analyzed HT in patients with ischemic stroke admitted to King Abdullah Medical City from August 2011 to April 2019. Data were analyzed using SPSS. Patients characteristics, procedures, treatments, and outcomes were reported.Results:There were 504 ischemic stroke patients. The HT was detected in 38 patients (8%). The median age was 66.5 (54.3 -77.5) years, and 24 (63%) were males. HT was classified as hemorrhagic infarction (HI) in 22 patients (58%) while 16 patients (42%) were parenchymal hematoma (PH). The most common risk factors noted were: hypertension (74%), diabetes mellitus (DM) (66%), hyperlipidemia (63%) and ischemic heart disease (IHD) (61%). Nine patients (23.6%) developed HT after receiving thrombolytic therapy. Only one patient (3%) died of HT patients.Conclusion:HT accounted for (8%) of all ischemic stroke patients. Old age, DM, hypertension, and hyperlipidemia are frequently encountered with stroke patients who developed HT. Follow up CT brain could be of value and could identify HT early to get better outcomes.

Factors Associated with Hemorrhagic Transformation in Infarctions Involving the Posterior Circulation System

Backgrounds and Purpose: Hemorrhagic transformation (HT) following stroke of the posterior circulation is a rare occurrence, and its risk factors remain relatively unknown. This study aimed at examining the rate of HT and its risk factors in patients enduring acute ischemic stroke in the territories of the vertebral, basilar, and posterior-cerebral arteries. Materials and Methods: A total of 217 consecutive patients the risk factors for ischemic stroke were recorded and comprehensive biochemical, cardiac assessments, and neuroimaging were performed. National Institutes of Health Stroke Scale (NIHSS) scores were calculated for each patient. Those with HT as documented with neuroimaging based on the European Cooperative Acute Stroke Study criteria and potential risk factors were assessed. Results: There were 217 participants with a mean age of 67.33 ± 12.44 years. Among 17 patients (7.8%) developing HT, 8 (47%) had parenchymal hematoma, and 9(53.5%) had hemorrhagic infarction. Cardioembolism was the most frequent etiological factor both in the overall group (31.0%) as well as in those with HT (41.2%). Factors that emerged as significant predictors of HT included high systolic (odds ratio [OR] 1.14; 95% confidence interval [CI] 1.08-1.20; P< .001) and diastolic blood pressure (P= .001) on the day of admission and the infarction volume of greater than or equal to 3.60 ± 3.29 cm³(OR 1.00, 95% CI 1.00-1.01; P< .001). While NIHSS scores were not significantly different on Day 1, HT patients had higher NIHSS scores at Day 10(OR 1.22; 95% CI 1.09-1.36; P< .001), and this difference was also reflected in mRS at the end of the 3 month period. Conclusion: HT is a rare complication of the infarction of the posterior circulation that is associated with increased morbidity and mortality. Identification of predictive factors for HT in patients with the acute infarction of the posterior circulation may facilitate patient selection for thrombolytic treatment.

Abstract WMP13: The Prediction of the Hemorrhagic Transformation Locations After Reperfusion Therapy in Acute Stroke Patients: A Magnetic Resonance Perfusion Study Using Deep Learning

Objective: Hemorrhagic transformation (HT) is a major complication of reperfusion therapy in acute stroke. We aim to explore the feasibility of HT location prediction from baseline magnetic resonance perfusion (MRP) source images. Methods: Consecutive acute ischemic stroke patients who had HT after reperfusion therapy (IV tPA and/or endovascular thrombectomy) were reviewed from two stroke centers. Patients with MRP and diffusion-weighted imaging (DWI) before and 24h after treatment and follow-up susceptibility weighted imaging (SWI) were included. The HT was depicted on follow-up SWI semi-automatically. The DWI lesions and HT were classified into 12 cerebral vascular territories (Fig 1A). Then a total of 80,000 tissue-voxels were extracted from both HT region and non-HT region randomly with the ratio of 1:1. Each voxel included a set of values of MRP source image and baseline DWI. Convolutional neural networks (CNN) were trained with 3-fold cross-validation. Prediction maps were generated from the CNN for each patient. The prevalence of HT after infarction and the sensitivity and specificity of HT prediction in each vascular territory were calculated. Results: Seventy-seven HT patients were analyzed (40 male, age 73 ±14 years, median baseline NIHSS score 14 [IQR 8-19], median onset-to-treatment time 242 min [IQR 152-355], median modified Rankin score 3 [IQR 1-4], 28 with Parenchymal hematoma). HT occurred most frequently in the territory of middle cerebral artery superficial branches (67.5%) and basal ganglia (37.6%), and least frequently in brain stem or thalamus (3.9%). HT was not evenly distributed throughout the vascular territories (Fig 1A). The best model was a locally-connected CNN (area under curve of 0.88). The average sensitivity and specificity for HT location prediction in anterior circulation were 89% and 60% (Fig 1BC). Conclusion: The CNN trained from DWI and MRP source images could predict the HT locations in acute ischemic stroke patients.

Computed Tomography Perfusion Alberta Stroke Program Early Computed Tomography Score Is Associated with Hemorrhagic Transformation after Acute Cardioembolic Stroke.

Alberta Stroke Program Early Computed Tomography (CT) score (ASPECTS) has been applied to CT perfusion (CTP) with good interrater agreement to predict early ischemic stroke, and it can be useful in decision making in acute ischemic stroke. The aim of the present study was to assess the predictive value of CTP ASPECTS of hemorrhagic transformation (HT) in acute cardioembolic stroke. This is a single-enter, retrospective study. All patients hospitalized with acute cardioembolic stroke from January 2008 to September 2013 were included. ASPECTS of baseline non-contrast CT, CTP maps of cerebral blood volume (CBV), cerebral blood flow, and mean transit time were collected from 52 consecutive patients with less than 12-h anterior circulation ischemic stroke. MRI scan was performed within 72 h of symptom onset after index stroke including T2*-weighted gradient echo to identify HT. For bleeding risk assessment, CTP and diffusion-weighted imaging ASPECTS were categorized into 0–7 or 8–10. Baseline characteristics, ASPCETS scores and HT were compared. Eighteen (34.6%) patients had HT and four (7.7%) developed symptomatic HT. On univariate analysis, the proportion of patients with CBV-ASPECTS 0–7 was significantly higher in HT patients as compared to patients without HT (44 versus 9%, P = 0.005). CBV ASPECTS 0–7 remained independent prognostic factors for HT after adjustment for clinical baseline variables. CBV ASPECTS could be of value to predict HT risk after acute cardioembolic stroke and may be a quick risk assessment approach before reperfusion therapy.

Abstract TP318: High White Blood Cell (WBC) Counts Are Predictive of tPA-related Hemorrhage

Background: Infection is a major complication of ischemic stroke and contributes to the morbidity and mortality of stroke patients. Although growing evidence highlights the close relationship between inflammation and coagulation/fibrinolysis cascades, little has been reported regarding the influence of tPA on human immune system. Here, we explore changes in white blood cell (WBC) counts pre/post IV tPA and their association with tPA-related hemorrhagic transformation (HT). Method: 308 tPA-treated ischemic stroke patients were recruited with IRB approval, of which 16 developed HT within 24 hr post tPA. Routine WBC was analyzed at 1 month pre stroke, during stroke onset and during the first 48 hr post tPA. Result: We found that WBC was significantly increased within 12 hr post IV tPA and gradually reduced after 24 hr (Figure 1A). However, compared with patients without HT, HT patients had much higher levels of WBC throughout tPA treatment, and their WBC remained above normal even after 48 hr (Figure 1B). More importantly, we also found that HT patients had already developed elevated WBC as early as 1 month before their stroke onset (Figure 1B), which was predictive of tPA-related HT (Figure 1C, ROC AUC = 0.889, p = 0.001). Furthermore, the early elevation in WBC post-tPA was not associated with clinical evidence of infection. Conclusion: Our results provide early clinical evidence that in addition to activating fibrinolytic pathway, tPA may also modulate immune system during stroke treatment. In addition, elevated WBC pre-stroke maybe a predictive marker of tPA-related hemorrhage. While elevated WBC early in ischemic stroke was reported to correlate with poorer clinical outcome, the transient peak in WBC post tPA in this patient cohort ultimately had better clinical outcome, and is of interest. Further studies are needed and ongoing to evaluate differential WBC, stroke severity and long term clinical outcome, and to understand the molecular basis of tPA in immune cell modulation.

Abstract TMP43: Routine Labs may Help Predict tPA-related Hemorrhagic Transformation: A Role for Serial Monitoring of Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) Post tPA

Background: Intravenous tissue plasminogen activator (tPA) is not routinely followed by blood work due to its reputed short half-life. While there has been a great deal of research on tPA’s extra-vascular effects on the neurovascular unit in the context of hemorrhagic complications, there is little clinical data on the intravascular efficacy of IV tPA - how and where it has its intended effect. Emerging data suggest that tPA may be most effective in the microvasculature and IV therapy may be a good adjunct to intra-arterial (IA) therapy. We previously found through proteomic profiling that the effects of IV tPA can last more than 72 hours. Now, we report that even routine blood labs can potentially help predict hemorrhagic transformation (HT). Method: 72 stroke patients treated with IV tPA were recruited post IRB approval. Clinical coagulation profiles (PT, PTT, fibrinogen and D-dimer) were performed at 12, 24, 72 hrs post IV tPA. Patients on medications (e.g. anticoagulants) or having other conditions (e.g. liver dysfunction, infection) that may affect these labs were excluded. Result: Compared to patients without HT, HT patients had significantly higher PT and PTT (Fig. 1 A,B) as early as 12 hrs post tPA administration and throughout the first 3 days of treatment. ROC analysis suggested PT and PTT at 12 and 24 hrs have potential to predict tPA-induced HT (Figure 1C,D. PT: AUC = 0.848, p = 0.001; PTT: AUC = 0.877; p = 0.003). Conclusion: Higher PT and PTT levels within 72 hours of IV tPA are early markers of HT post IV tPA in acute ischemic stroke. Whether these routine labs have value in symptomatic hemorrhage will require further study in a larger cohort. But this proof-of-concept study suggests that tPA efficacy can potentially be followed in real time, even with routine labs. The development of a reliable blood test would be of clinical utility to gauge thrombolytic efficacy in real time to guide and/or triage adjunct treatments.

Initial research on the relationship between let-7 family members in the serum and massive cerebral infarction

Eighty-eight ischemic stroke patients with massive cerebral infarction (MCI) who met our selection criteria were included in this study. MCI was assessed using the Glasgow Coma Scale (GCS) at hospital admission and at 2weeks. The sera of all patients and controls were sampled at 48h after the patients' attacks, and the sera of patients with MCI who had no severe cardiopulmonary complications, including those with hemorrhagic transformation (HT), were sampled again at 2weeks. The relative expression of let-7 miRNA in the serum was determined by real-time qRT-PCR, and the blood levels of lipids, glucose, high-sensitivity C-reactive protein (hs-CRP), homocysteine and blood pressure were measured at admission. Interleukin-6 (IL-6) levels were detected by ELISA, and a luciferase assay was performed to confirm that IL-6 was a gene target of let-7. The relative expression of let-7f was significantly down-regulated in MCI without HT patients compared with controls (P<0.001), and it was positively correlated with GCS (P<0.01) and negatively correlated with hs-CRP (P<0.01). The relative expression of let-7f was significantly up-regulated in MCI patients with HT (P<0.01). IL-6 is a direct target gene for let-7f, and IL-6 expression was increased in MCI without HT patients compared to controls (P<0.01). The expression of let-7f in serum is associated with MCI without HT, which specifically inhibits IL-6. This suggests that let-7f may control inflammation in patients with MCI without HT.

Risk Factors for Hemorrhagic Transformation in Patients with Acute Middle Cerebral Artery Infarction.

Hemorrhagic transformation (HT) after acute ischemic stroke (AIS) can be seen at any time following ischemic stroke. Although HT usually occurs as a complication of antithrombotic, anticoagulant, or thrombolytic treatments, it can also occur spontaneously. We aimed to investigate the occurrence of early HT and its relevant risk factors in patients diagnosed with acute middle cerebral artery (MCA) infarction who were not treated with thrombolytic agents. We recruited 171 patients with acute MCA infarction between January 2011 and July 2012 who were not treated with thrombolytic agents and were suitable to our inclusion criteria. Controlled neuroimaging was performed immediately in patients with deterioration, otherwise on day 7 following stroke. All patients were investigated for AIS risk factors and biochemical analyses were performed. Patients with HT in controlled neuroimaging were grouped both clinically (i.e., symptomatic or asymptomatic) and radiologically, according to "European Cooperative Acute Stroke Radiological Study" (ECASS), and risk factors were examined. We enrolled 171 patients [94 men (55%) and 77 women (45%)] in the study. HT developed in 37 patients (21.63%). In terms of risk factor analysis, the most frequent etiological factor was atherosclerosis in AIS patients (50.3%). National Institutes of Health Stroke Scale scores were significantly higher both in sHT patients according to asHT patients and in HT patients on day 7 compared with their initial scores. Serum low-density lipoprotein (LDL-C), triglycerides (TG), and total cholesterol (TC) levels were significantly lower in patients with HT (p<.001). HT is a major complication in AIS that considerably increases the morbidity and mortality. To reduce the occurrence of HT, risk factors for each patient population should be determined. Acute thrombolytic therapy should be used cautiously in high-risk patients, and appropriate alternative therapies should be revised in them.