Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage – A multicentre subanalysis of the German PBM Network Registry

Purpose Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. Methods This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 until 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. Results A total of n = 9,081 patients were analysed (aSAH n = 5,008; ICH n = 4,073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR= 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR= 1.48 in aSAH, OR= 1.53 in ICH, p < 0.001) and for several postoperative complications. Conclusions Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH. Trial registration: ClinicalTrials.gov, NCT02147795, https://clinicaltrials.gov/ct2/show/NCT02147795

High haemoglobin levels and mortality in males with intracerebral haemorrhage: a retrospective cohort study

ObjectivesTo examine the association between high haemoglobin levels and outcomes in intracerebral haemorrhage (ICH) in a multicentre cohort study.DesignProspective multicentre cohort study.Settings21 tertiary hospitals across mainland China.ParticipantsA total of 5318 consecutive in-hospital spontaneous ICH patients were recruited between January 2012 and June 2016.Primary and secondary outcome measuresHaemoglobin levels were measured on admission. Binary or ordinary logistic regression was used to evaluate the independent relationship of haemoglobin level with clinical outcomes at 3 months, measured as death or disability. Restricted cubic spline regression was fitted to examine the potential non-linear shape of the dose–response curve between the whole haemoglobin levels and 3-month poor outcomes.ResultsA total of 5031 patients with ICH were analysed (64.3% male; mean age (SD), 57.8 (15.2) years). We found that the highest haemoglobin quintile was associated with poor outcomes 3 months in males (adjusted OR (aOR) 1.65, 95% CI 1.21 to 2.25) but not in females, which was also observed in the pooled analysis of three subcohorts in male patients (average aOR 1.70, 95% CI 1.23 to 2.33). The spline regression suggested a non-linear association between haemoglobin levels and outcomes and a linear relationship was observed between an elevated haemoglobin level and 3-month disability/death in males (haemoglobin level per 10 g/L: aOR 1.24, 95% CI 1.10 to 1.40, p<0.001), which was mediated by larger haematoma volume (effect size: 0.115, 95% CI 0.012 to 0.231).ConclusionsThis study found a sex-specific association between an elevated haemoglobin level and poor 3-month outcomes, which might be mediated by larger haematoma volume.

Adjusted Morbidity Groups and Intracerebral Haemorrhage: A Retrospective Primary Care Cohort Study

Background: Intracerebral haemorrhage rates are increasing among highly complex, elderly patients. The main objective of this study was to identify modifiable risk factors of intracerebral haemorrhage. Methods: Multicentre, retrospective, community-based cohort study was conducted, including patients in the Adjusted Morbidity Group 4 with no history of intracerebral haemorrhage. Cases were obtained from electronic clinical records of the Catalan Institute of Health and were followed up for five years. The primary outcome was the occurrence of intracerebral haemorrhage during the study period. Demographic, clinical and pharmacological variables were included. Logistic regression analyses were carried out to detect prognostic variables for intracerebral haemorrhage. Results: 4686 subjects were included; 170 (3.6%) suffered an intracerebral haemorrhage (85.8/10,000 person–year [95% CI 85.4 to 86.2]). The HAS-BLED score for intracerebral haemorrhage risk detection obtained the best AUC (0.7) when used in the highest complexity level (cut-off point ≥3). Associated independent risk factors were age ≥80 years, high complexity and use of antiplatelet agents. Conclusions: The Adjusted Morbidity Group 4 is associated with a high risk of intracerebral haemorrhage, particularly for highly complex patients and the use of antiplatelet agents. The risk of bleeding in these patients must be closely monitored.

Impact of COVID-19 pandemic on haemorrhagic stroke admissions: a systematic review and meta-analysis

Background and purposeCOVID-19 pandemic, a global health crisis, is disrupting the present medical environment. This systematic review and meta-analysis aimed to evaluate the impact of the COVID-19 pandemic on stroke hospitalisations, especially haemorrhagic stroke.MethodsThe EMBASE, PubMed, Web of Science, Elsevier, Medline, Cochrane Library and Google Scholar electronic databases were searched for all relevant studies. Two researchers independently screened the studies, extracted data and assessed the quality of the included studies. Odds ratio (OR), total events, OR and 95% CI were considered as the effect size. A fixed-effects model was used to pool the study-specific estimate. The present study was performed by using Review Manager (V.5.3.0) software. We assessed the risk of bias using the Newcastle–Ottawa Scale.ResultsA total of 17 studies with 14 445 cases were included. Overall, the number of stroke admissions is lower in the pandemic period versus the control period (6252 vs 8193). The difference of haemorrhagic stroke is significant, with 1233 of 6252 cases in the pandemic group and 1621 of 8193 cases in the control group. Intracerebral haemorrhage is present in 461 of 1948 cases in the pandemic group and 618 of 2734 cases in the control group. As for subarachnoid haemorrhage, the difference between the two groups is significant, with 70 of 985 cases in the pandemic group and 202 of 1493 cases in the control group.ConclusionsThe number of stroke admissions is lower in the pandemic period compared with the control period. There is a higher rate of haemorrhagic stroke in the pandemic period. Subgroup analysis identifies a significant increase in the occurrence of intracerebral haemorrhage in the pandemic period. Due to limited data and the impact of a single article, the impact of COVID-19 pandemic on subarachnoid haemorrhage is unclear.

Background incidence rates of hospitalisations and emergency department visits for thromboembolic and coagulation disorders in Ontario, Canada for COVID-19 vaccine safety assessment: a population-based retrospective observational study

ObjectiveThe objective of this study was to estimate background rates of selected thromboembolic and coagulation disorders in Ontario, Canada.DesignPopulation-based retrospective observational study using linked health administrative databases. Records of hospitalisations and emergency department visits were searched to identify cases using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada diagnostic codes.ParticipantsAll Ontario residents.Primary outcome measuresIncidence rates of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, deep vein thrombosis, pulmonary embolism, idiopathic thrombocytopaenia, disseminated intravascular coagulation and cerebral venous thrombosis during five prepandemic years (2015–2019) and 2020.ResultsThe average annual population was 14 million with 51% female. The mean annual rates per 100 000 population during 2015–2019 were 127.1 (95% CI 126.2 to 127.9) for ischaemic stroke, 22.0 (95% CI 21.6 to 22.3) for intracerebral haemorrhage, 9.4 (95% CI 9.2 to 9.7) for subarachnoid haemorrhage, 86.8 (95% CI 86.1 to 87.5) for deep vein thrombosis, 63.7 (95% CI 63.1 to 64.3) for pulmonary embolism, 6.1 (95% CI 5.9 to 6.3) for idiopathic thrombocytopaenia, 1.6 (95% CI 1.5 to 1.7) for disseminated intravascular coagulation, and 1.5 (95% CI 1.4 to 1.6) for cerebral venous thrombosis. Rates were lower in 2020 than during the prepandemic years for ischaemic stroke, deep vein thrombosis and idiopathic thrombocytopaenia. Rates were generally consistent over time, except for pulmonary embolism, which increased from 57.1 to 68.5 per 100 000 between 2015 and 2019. Rates were higher for females than males for subarachnoid haemorrhage, pulmonary embolism and cerebral venous thrombosis, and vice versa for ischaemic stroke and intracerebral haemorrhage. Rates increased with age for most of these conditions, but idiopathic thrombocytopaenia demonstrated a bimodal distribution with incidence peaks at 0–19 years and ≥60 years.ConclusionsOur estimated background rates help contextualise observed events of these potential adverse events of special interest and to detect potential safety signals related to COVID-19 vaccines.

Tranexamic acid for intracerebral haemorrhage within 2 hours of onset: protocol of a phase II randomised placebo-controlled double-blind multicentre trial

RationaleHaematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth.Methods and designStopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework.HypothesisIn patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimatesA sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.InterventionParticipants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo.Primary efficacy measureThe primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.DiscussionWe describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.

Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis

Background: The causal relationship between childhood obesity and stroke remains unclear. Our objective was to elucidate the causal relationship between childhood obesity and the risk of stroke and its subtypes by performing Mendelian randomisation (MR) analyses.Methods: Genetic instruments for childhood obesity were obtained from a genome-wide association study (GWAS) of 13,848 European participants. Summary level data for stroke, intracerebral haemorrhage, ischaemic stroke (IS), and its subtypes were evaluated using the MEGASTROKE GWAS dataset, which included 446,696 European adults. Inverse-variance weighting, weighted-median analysis, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and MR-Robust Adjusted Profile Score were applied in this MR analysis. The leave-one-out sensitivity test, MR-PRESSO Global test, and Cochran’s Q test were conducted to confirm the accuracy and robustness of our results.Results: Genetic evaluations revealed that childhood obesity was associated with a higher risk of stroke (OR = 1.04, 95%CI: 1.01–1.07, p = 0.005) and IS (OR = 1.05, 95%CI: 1.02–1.08, p = 0.003), but not with intracerebral haemorrhage (ICH, OR = 0.93, 95%CI: 0.80–1.09, p = 0.39). In the subtype analysis, childhood obesity was also associated with large artery stroke (LAS, OR = 1.12, 95%CI: 1.02–1.22, p = 0.016) but not with cardioembolic stroke (OR = 1.06, 95%CI: 0.96–1.18, p = 0.21) and small vessel stroke (OR = 1.06, 95%CI: 0.98–1.15, p = 0.17). These results were stable in the sensitivity analysis and remained significant after Bonferroni correction.Conclusion: Our study provides evidence that childhood obesity is associated with a higher risk of stroke, IS, and LAS. The prevention of stroke, especially IS and LAS, should be promoted in populations with childhood obesity.