Late-onset aspirin-related hemolysis and subsequent subdural hemorrhage in patient with glucose-6-phosphate dehydrogenase deficiency.

Key Clinical Message: Aspirin-related hemolysis in G6PD deficiency could be late-onset during long-term administration. Hemolytic anemia could continue for a relatively long time in elder patient with G6PD deficiency, which might be related to other adverse events. Abstract: Aspirin-related hemolysis in G6PD-deficient individuals was generally reported among patients who received high-dose supplements within several days after ingestion. The safety of long-term and low-dose (50-325 mg/day) aspirin in patients coexist G6PD deficiency and cardiovascular disease is neglected in clinical practice. In this case, we observed a late-onset hemolysis and subsequent fatal subdural hemorrhage in one G6PD-deficient individual who had received long-term and low-dose aspirin. An 83-year-old male was diagnosed with acute ischemic stroke and treated with 100 mg/day aspirin at the emergency room. After admission, the patient was diagnosed with severe G6PD deficiency based on enzyme activity, but no hemolysis occurred within 10-day aspirin therapy in the hospital. Hence, 100 mg/day aspirin was continued on discharge. Two months later, the patient presented acute hemolysis manifested as fatigue, dark urine, and moderate jaundice. Although hemolysis was self-limit in a few days, hemoglobin decline continued for 20 days until a fatal subdural hemorrhage occurred. Our study indicated aspirin-related hemolysis could be late-onset in G6PD-deficient individual even receiving low-dose treatment and is probably linked to subsequent major bleeding events.

High-throughput sequencing-based Detection of Japanese encephalitis virus and its effect on micro ribonucleic acid.

it was to explore the mechanism of Japanese encephalitis virus (JEV) and micro ribonucleic acid (miRNA) under high-throughput sequencing. 20 experimental mice, with good growth status and no disease infection, were selected. The cells used in the experiment included mouse microglial cell line (BV2), mouse neuroblastoma cell line (NA), and mouse brain endothelial cell line (bEnd.3). JEV titration was performed with JEV-infected cells, ribonucleic acid (RNA) in the cells was extracted, and finally the miRNA high-throughput sequencing data was analyzed. Agarose gel electrophoresis showed that the 28S and 18S electrophoresis bands were bright. Among the miRNAs detected in mouse brain tissues, 2986 were down-regulated and 1251 were up-regulated. Among miRNAs detected in NA cells, 4238 the decreasing expression and 2356 were expressed increasingly. In reducing miRNA expression, 1 multiplicity of infection (MOI) of P3 strain infection was more significant than 0.1 MOI. 10 miRNAs with significantly decreasing expression were miR-466d-3p, miR-381-3p, miR-540-3p, miR-466a-3p, miR-467a-3p, miR-574-5p, miR-199a-5p, miR-467a-5p, miR-674-5p, and miR-376b-3p. These were all obviously down-regulated in JEV-infected BV2, NA, and bEnd.3 neurons. High-throughput sequencing of JEV-infected mouse brain tissues and mouse neuronal cells found that JEV infection led to down-regulation of overall miRNA expression in host cells.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03539445.

Glucose-6-phosphate dehydrogenase deficiency and intracranial atherosclerotic stenosis in stroke patients.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is a major cause of stroke in Asian countries. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a hereditary enzyme defect prevalent in Asian countries, has been associated with atherosclerotic cardiovascular disease and worse poststroke outcomes. However, the impact of G6PD deficiency on ICAS remains unclear. We aimed to compare the risk of ICAS in stroke patients with and without G6PD deficiency in a Chinese cohort. METHODS: We prospectively and consecutively recruited stroke patients from four centers in China. All patients received intracranial artery assessment by magnetic resonance/computed tomography angiography or digital subtraction angiography, as well as G6PD enzyme evaluation. The prevalence, burden, and characteristics of ICAS were compared between patients with and without G6PD deficiency using multivariate regression analysis. RESULTS: Among 1593 patients, 116 (63.7%) of 182 patients with G6PD deficiency and 714 (50.6%) of 1411 patients with normal G6PD levels were identified as ICAS. Age, hypertension, diabetes, and G6PD deficiency were independent predictors of ICAS. Among patients with ICAS, G6PD-deficient individuals were more likely to have multiple (≥2 segments) intracranial stenosis (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.25-2.81, p = 0.002). G6PD deficiency increased the risk of ICAS in patients who were male (OR = 1.82, 95% CI = 1.24-2.66, p = 0.002), aged ≥70 years (OR = 2.40, 95% CI = 1.33-4.31, p = 0.004), or hypertensive (OR = 1.88, 95% CI = 1.28-2.77, p = 0.001). CONCLUSIONS: Stroke patients with G6PD deficiency have a higher prevalence and ICAS burden than those with normal G6PD, particularly those who are male, older, and hypertensive.

Association between aspirin-induced hemoglobin decline and outcome after acute ischemic stroke in G6PD-deficient patients.

AIMS: The risk of hemoglobin decline induced by low-dose aspirin in glucose-6-phosphate dehydrogenase (G6PD) deficiency remains unknown, and its influence on stroke outcome remains to be investigated. This study aimed to evaluate the effect of G6PD deficiency on hemoglobin level during aspirin treatment and its association with outcome after acute ischemic stroke. METHODS: In total, 279 patients (40 G6PD-deficient and 239 G6PD-normal) with acute ischemic stroke treated with aspirin 100 mg/day from a cohort study were examined. The primary safety endpoint was a hemoglobin decline ≥25 g/L or 25% from baseline within 14 days after aspirin treatment. Poor outcomes were defined as a modified Rankin Scale score ≥2 at 3 months. The χ2 test was used to compare stroke outcomes, and multivariate logistic regression analyses were performed to analyze the association between hemoglobin level and outcomes. RESULTS: The G6PD-deficient group had lower baseline hemoglobin and tended to develop comorbid pulmonary infection more frequently (p < 0.05). The proportion of patients with hemoglobin decline ≥25 g/L or 25% from baseline (15.0% vs. 3.3%; p = 0.006) and anemia (30.0% vs. 14.6%; p = 0.016) after aspirin treatment was higher in the G6PD-deficient group, which was accompanied by a more significant bilirubin increase. The rate of poor functional outcomes at 3 months after acute ischemic stroke was higher in the G6PD-deficient group (Risk ratio = 1.31 [95% confidence interval (CI) = 1.10-1.56]; p = 0.017). Confounder-adjusted analysis showed that lower hemoglobin levels (odds ratio = 0.98 [95% CI = 0.96-0.99]; adjusted p = 0.009) increased the risk of poor functional outcomes. CONCLUSION: Hemoglobin decrease with bilirubin increase after aspirin treatment in patients with G6PD deficiency suggests hemolysis, which may influence stroke prognosis. The risk of hemoglobin decline should be carefully monitored in G6PD-deficient patients with ischemic stroke taking aspirin.

Safety and efficacy of low-dose aspirin in ischemic stroke patients with different G6PD conditions.

BACKGROUND AND PURPOSE: Aspirin is the first recommended antiplatelet agent to prevention secondary stroke, but its safety and efficacy in stroke patients with glucose-6-phosphate dehydrogenase deficiency remain unclear. We sought to evaluate its safety and efficacy in ischemic stroke patients with and without glucose-6-phosphate dehydrogenase deficiency. METHODS: Patients with ischemic stroke receiving aspirin (100 mg/day) for three months were recruited for a multicenter, prospective, cohort study. Blood glucose-6-phosphate dehydrogenase activity was examined after stroke. Safety outcomes including acute hemolysis, moderate-to-severe bleeding, and death (vascular, all-cause), and efficacy outcome indicated as stroke recurrence were evaluated at three months. Risk factors associated with moderate-to-severe bleeding and all-cause death were determined using multivariate or Cox regression analysis. RESULTS: Among the included 1121 patients, 81 of 130 glucose-6-phosphate dehydrogenase deficient and 576 of 991 glucose-6-phosphate dehydrogenase normal patients received aspirin for three months. Acute hemolysis was observed in one of the glucose-6-phosphate dehydrogenase deficient and in none of the glucose-6-phosphate dehydrogenase normal patients (p = 0.876). The rates of moderate-to-severe bleeding were 2.5% and 0.3% (p = 0.045), and the percentages of all-cause death were 6.2% and 1.4% (p = 0.008) in the glucose-6-phosphate dehydrogenase deficient and glucose-6-phosphate dehydrogenase normal patients. Stroke recurrence rate was similar in the two groups (2.5% vs. 1.7%; p = 0.608). Glucose-6-phosphate dehydrogenase deficiency was significantly associated with increased risk of moderate-to-severe bleeding (adjust p = 0.048) and all-cause death during aspirin use (adjust p = 0.008). CONCLUSIONS: Long-term low-dose aspirin therapy might relate to worse safety outcomes in patients with glucose-6-phosphate dehydrogenase deficiency and large clinical trials are needed to further confirm these findings.

Glucose-6-phosphate dehydrogenase deficiency and stroke outcomes.

OBJECTIVE: To assess the risk of glucose-6-phosphate dehydrogenase (G6PD) on stroke prognosis, we compared outcomes between patients with stroke with and without G6PD deficiency. METHODS: The study recruited 1,251 patients with acute ischemic stroke. Patients were individually categorized into G6PD-deficiency and non-G6PD-deficiency groups according to G6PD activity upon admission. The primary endpoint was poor outcome at 3 months defined by a modified Rankin Scale (mRS) score ≥2 (including disability and death). Secondary outcomes included the overall mRS score at 3 months and in-hospital death and all death within 3 months. Logistic regression and Cox models, adjusted for potential confounders, were fitted to estimate the association of G6PD deficiency with the outcomes. RESULTS: Among 1,251 patients, 150 (12.0%) were G6PD-deficient. Patients with G6PD deficiency had higher proportions of large-artery atherosclerosis (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.09-2.17) and stroke history (OR 1.93, 95% CI 1.26-2.90) compared to the non-G6PD-deficient group. The 2 groups differed significantly in the overall mRS score distribution (adjusted common OR 1.57, 95% CI 1.14-2.17). Patients with G6PD deficiency had higher rates of poor outcome at 3 months (adjusted OR 1.73, 95% CI 1.08-2.76; adjusted absolute risk increase 13.0%, 95% CI 2.4%-23.6%). The hazard ratio of in-hospital death for patients with G6PD-deficiency was 1.46 (95% CI 1.37-1.84). CONCLUSIONS: G6PD deficiency is associated with the risk of poor outcome at 3 months after ischemic stroke and may increase the risk of in-hospital death. These findings suggest the rationality of G6PD screening in patients with stroke.