Microglial FoxO3a deficiency ameliorates ferroptosis-induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase-1.

Microglial HO-1 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co-located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a/ATG-mediated autophagy and HO-1 signalling resulting in ferroptosis in vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf-A1 or HO-1 inhibitor ZnPP protected against hemin-induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a/ATG-mediated autophagy and HO-1 signalling pathway. Knock-down of FoxO3a inhibited autophagy and prevented hemin-induced ferroptosis dependent of HO-1 signalling. We first showed that hemin stimulated microglial FoxO3a/HO-1 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro-inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis-induced striatum injury in the autologous blood-induced ICH model. We demonstrate, for the first time, that FoxO3a/ATG-mediated autophagy and HO-1 play an important role in microglial activation and ferroptosis-induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH.

Machine learning and deep learning to identifying subarachnoid haemorrhage macrophage-associated biomarkers by bulk and single-cell sequencing.

We investigated subarachnoid haemorrhage (SAH) macrophage subpopulations and identified relevant key genes for improving diagnostic and therapeutic strategies. SAH rat models were established, and brain tissue samples underwent single-cell transcriptome sequencing and bulk RNA-seq. Using single-cell data, distinct macrophage subpopulations, including a unique SAH subset, were identified. The hdWGCNA method revealed 160 key macrophage-related genes. Univariate analysis and lasso regression selected 10 genes for constructing a diagnostic model. Machine learning algorithms facilitated model development. Cellular infiltration was assessed using the MCPcounter algorithm, and a heatmap integrated cell abundance and gene expression. A 3 × 3 convolutional neural network created an additional diagnostic model, while molecular docking identified potential drugs. The diagnostic model based on the 10 selected genes achieved excellent performance, with an AUC of 1 in both training and validation datasets. The heatmap, combining cell abundance and gene expression, provided insights into SAH cellular composition. The convolutional neural network model exhibited a sensitivity and specificity of 1 in both datasets. Additionally, CD14, GPNMB, SPP1 and PRDX5 were specifically expressed in SAH-associated macrophages, highlighting its potential as a therapeutic target. Network pharmacology analysis identified some targeting drugs for SAH treatment. Our study characterised SAH macrophage subpopulations and identified key associated genes. We developed a robust diagnostic model and recognised CD14, GPNMB, SPP1 and PRDX5 as potential therapeutic targets. Further experiments and clinical investigations are needed to validate these findings and explore the clinical implications of targets in SAH treatment.

Acquired haemophilia A in paediatric patients: A retrospective French cohort of eight cases.

Acquired haemophilia A (AHA) is a rare haemorrhagic disease characterised by new-onset haemorrhagic symptoms associated with a dramatic decrease in factor VIII levels and an anti-factor VIII neutralising autoantibody concentration >0.6 Bethesda units. Elderly people are often affected, whereas children are rarely affected; the paediatric incidence reported in the literature is about 0.045 case/million/year. For some time, the paediatric standard of care has been that for adults, but clinicians have often reported poor outcomes. Here, we describe the largest retrospective paediatric AHA cohort assembled to date, including eight patients diagnosed in France from 2000 to 2020.

Impact of non-driver gene mutations on thrombo-haemorrhagic events in ET patients.

Risk-adapted therapy is recommended to prevent major clinical complications, such as thrombo-haemorrhagic events, in patients with essential thrombocythaemia (ET). In this study, we analysed the association between non-driver gene mutations and thrombo-haemorrhagic events in 579 patients with ET. ASXL1 and TP53 mutations were frequently identified in patients with ET complicated by thrombosis (22.7% and 23.1%, respectively), and the DNMT3A mutation was frequently identified in patients who experienced haemorrhage (15.2%). Multivariate analyses of thrombosis-free survival (TFS) revealed that ASXL1 and TP53 mutations are associated with thrombosis (hazard ratio [HR] = 3.140 and 3.752 respectively). Patients harbouring the ASXL1 or TP53 mutation had significantly worse TFS rates than those without mutation (p = 0.002 and p < 0.001 respectively). Furthermore, JAK2V617F-mutated patients with accompanying ASXL1 mutations showed significantly shorter TFS compared with those without ASXL1 mutations (p = 0.003). Multivariate analyses of haemorrhage-free survival (HFS) revealed that the DNMT3A mutation (HR = 2.784) is associated with haemorrhage. DNMT3A-mutated patients showed significantly shorter HFS than those without the mutation (p = 0.026). Non-driver gene mutations should be considered in treatment strategies and may provide important information for personalised treatment approaches.

Past meets present: Reviving 80-year-old Canadian dried serum from World War II and its significance in advancing modern freeze-dried plasma for prehospital management of haemorrhage.

During World War II, Charles H. Best utilized Charles R. Drew's plasma isolation and drying technique to lead Canada's initiative to provide dried serum as a means of primary resuscitation for British casualties on the frontlines. Serum was likely utilized over plasma for its volume expansion properties without the risk of clotting during prolonged storage. We reconstituted dried serum from 1943 and discovered intact albumin, as well as anti-thrombin, plasminogen, protein C and protein S activity. Proteomic analysis identified 71 proteins, most prominent being albumin, and positive for hepatitis B by serological testing. Transmission of blood-borne diseases ended the programme, until modern advances in testing and pathogen reduction revived this technology. We tested the latest iteration of Canadian freeze-dried plasma (FDP), which was stored for 4 years, and demonstrated that its clotting capacity remained equivalent to fresh frozen plasma. We recommend that FDP is a strong alternative to contemporary prehospital resuscitation fluids (e.g. normal saline/lactated Ringer's) in managing prehospital haemorrhage where whole blood is unavailable.

FGF21 attenuates neuroinflammation following subarachnoid hemorrhage through promoting mitophagy and inhibiting the cGAS-STING pathway.

BACKGROUND: Subarachnoid hemorrhage (SAH) represents a form of cerebrovascular event characterized by a notable mortality and morbidity rate. Fibroblast growth factor 21 (FGF21), a versatile hormone predominantly synthesized by the hepatic tissue, has emerged as a promising neuroprotective agent. Nevertheless, the precise impacts and underlying mechanisms of FGF21 in the context of SAH remain enigmatic. METHODS: To elucidate the role of FGF21 in inhibiting the microglial cGAS-STING pathway and providing protection against SAH-induced cerebral injury, a series of cellular and molecular techniques, including western blot analysis, real-time polymerase chain reaction, immunohistochemistry, RNA sequencing, and behavioral assays, were employed. RESULTS: Administration of recombinant fibroblast growth factor 21 (rFGF21) effectively mitigated neural apoptosis, improved cerebral edema, and attenuated neurological impairments post-SAH. Transcriptomic analysis revealed that SAH triggered the upregulation of numerous genes linked to innate immunity, particularly those involved in the type I interferon (IFN-I) pathway and microglial function, which were notably suppressed upon adjunctive rFGF21 treatment. Mechanistically, rFGF21 intervention facilitated mitophagy in an AMP-activated protein kinase (AMPK)-dependent manner, thereby preventing mitochondrial DNA (mtDNA) release into the cytoplasm and dampening the activation of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Conditional knockout of STING in microglia markedly ameliorated the inflammatory response and mitigated secondary brain injuries post-SAH. CONCLUSION: Our results present the initial evidence that FGF21 confers a protective effect against neuroinflammation-associated brain damage subsequent to SAH. Mechanistically, we have elucidated a novel pathway by which FGF21 exerts this neuroprotection through inhibition of the cGAS-STING signaling cascade.

Histological chorioamnionitis and pathological stages on very preterm infant outcomes.

AIMS: Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age. METHODS: Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes. RESULTS: The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05). CONCLUSIONS: Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.

Upper gastrointestinal haemorrhage patients' survival: A causal inference and prediction study.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a common medical emergency. This study aimed to develop models to predict critically ill patients with upper GI bleeding in-hospital and 30-day survival, identify the correlation factor and infer the causality. METHODS: A total of 2898 patients with upper GI bleeding were included from the Medical Information Mart for Intensive Care-IV and eICU-Collaborative Research Database, respectively. To identify the most critical factors contributing to the prognostic model, we used SHAP (SHapley Additive exPlanations) for machine learning interpretability. We performed causal inference using inverse probability weighting for survival-associated prognostic factors. RESULTS: The optimal model using the light GBM (gradient boosting algorithm) algorithm achieved an AUC of .93 for in-hospital survival, .81 for 30-day survival in internal testing and .87 for in-hospital survival in external testing. Important factors for in-hospital survival, according to SHAP, were SOFA (Sequential organ failure assessment score), GCS (Glasgow coma scale) motor score and length of stay in ICU (Intensive critical care). In contrast, essential factors for 30-day survival were SOFA, length of stay in ICU, total bilirubin and GCS verbal score. Our model showed improved performance compared to SOFA alone. CONCLUSIONS: Our interpretable machine learning model for predicting in-hospital and 30-day mortality in critically ill patients with upper gastrointestinal bleeding showed excellent accuracy and high generalizability. This model can assist clinicians in managing these patients to improve the discrimination of high-risk patients.

The influence of epigenetic biological age on key complications and outcomes in aneurysmal subarachnoid haemorrhage.

BACKGROUND: We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality. METHODS: We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum's, Horvath's, Levine's and both versions of Zhang's clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3-5) and mortality using linear regression models adjusted for confounders. RESULTS: Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath's and Levine's clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum's clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks. CONCLUSIONS: Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes.

Test-retest reliability of transfer function analysis metrics for assessing dynamic cerebral autoregulation to spontaneous blood pressure oscillations.

Transfer function analysis (TFA) is a widely used method for assessing dynamic cerebral autoregulation in humans. In the present study, we assessed the test-retest reliability of established TFA metrics derived from spontaneous blood pressure oscillations and based on 5 min recordings. The TFA-based gain, phase and coherence in the low-frequency range (0.07-0.20 Hz) from 19 healthy volunteers, 37 patients with subarachnoid haemorrhage and 19 patients with sepsis were included. Reliability assessments included the smallest real difference (SRD) and the coefficient of variance for comparing consecutive 5 min recordings, temporally separated 5 min recordings and consecutive recordings with a minimal length of 10 min. In healthy volunteers, temporally separating the 5 min recordings led to a 0.38 (0.01-0.79) cm s-1 mmHg-1 higher SRD for gain (P = 0.032), and extending the duration of recordings did not affect the reliability. In subarachnoid haemorrhage, temporal separation led to a 0.85 (-0.13 to 1.93) cm s-1 mmHg-1 higher SRD (P = 0.047) and a 20 (-2 to 41)% higher coefficient of variance (P = 0.038) for gain, but neither metric was affected by extending the recording duration. In sepsis, temporal separation increased the SRD for phase by 94 (23-160)° (P = 0.006) but was unaffected by extending the recording. A recording duration of 8 min was required to achieve stable gain and normalized gain measures in healthy individuals, and even longer recordings were required in patients. In conclusion, a recording duration of 5 min appears insufficient for obtaining stable and reliable TFA metrics when based on spontaneous blood pressure oscillations, particularly in critically ill patients with subarachnoid haemorrhage and sepsis.

Bleeding control improves after switching to emicizumab: Real-world experience of 177 children in the PedNet registry.

INTRODUCTION: Despite the rapid uptake of emicizumab in the paediatric haemophilia A (HA) population, real-world data on the safety and efficacy is limited. AIM: To report on bleeding and safety in paediatric patients receiving emicizumab prophylaxis. METHODS: Data were extracted from the multicentre prospective observational PedNet Registry (NCT02979119). Children with haemophilia A, and ≥50 FVIII exposures or inhibitors present receiving emicizumab maintenance therapy were analysed. Data were summarized as medians with interquartile range (IQR, P25-P75). Mean (95% confidence interval (CI)), annualized (joint) bleeding rate (A(J)BR) during emicizumab and ≤2 years before emicizumab prophylaxis were modelled and compared using negative binomial regression. RESULTS: Total of 177 patients started emicizumab at median 8.6 years (IQR 4.8-13.1), most had no FVIII inhibitors (64%). Follow up before emicizumab was median: 1.68 years (IQR: 1.24-1.90) and during emicizumab: 1.32 years (IQR: .94-2.11). In patients without inhibitors, mean ABR reduced after starting emicizumab from 2.41 (CI 1.98-2.95) to 1.11 (CI .90-1.36, p < .001), while AJBR reduced from.74 (CI .56-.98) to.31 (CI .21-.46, p < .001). Concordantly, in patients with inhibitors, mean ABR reduced from 5.08 (CI 4.08-6.38) to .75 (CI .56-1.01, p < .001), while AJBR reduced from 1.90 (CI 1.42-2.58) to .34 (CI .21-.56, p < .001). Five emicizumab-related adverse events were reported (3% of the cohort), including one patient with antidrug antibodies. CONCLUSION: This study showed improved bleeding control compared to previous treatment and a favourable safety profile during emicizumab therapy in paediatric haemophilia A patients.

Severe haemorrhages leading to a diagnosis of rare bleeding disorder occur at a very young age: A study from the FranceCoag network.

INTRODUCTION: In the context of severe unexplained haemorrhage (SH), it is usual to seek haematological evaluation and investigate for an inherited rare bleeding disorder (IRBD). In such circumstances, appropriate screen can discriminate between IRBD and suspected child abuse. Yet, little information is available about the frequency of SH in the population of patients with IRBD. AIM: To collect epidemiologic data about SH and IRBD. METHOD: The database of the FranceCoag network has collected information about IRBD since January 2004. Based on data gathered up to 16 March 2022, a retrospective search was conducted for of SH events having occurred before or at the time of IRBD diagnosis. Demographics and diagnosis circumstances were retrieved, as well as information about SH, defined as any life-threatening bleeding or intracranial haemorrhage. RESULTS: Among the 13,433 patients of the database, 109 (0.8%) fulfilled inclusion criteria including a known date of IRBD diagnosis, haemophilia A or B (HA/HB) being the most frequent (82.5%). IRBD was discovered as a consequence of an SH event in 82.6% of the cases while CNS was involved in 55%. Severe and moderate HA/HB and other severe IRBD presented significantly more intracranial haemorrhage (p < .02) and a lower age at diagnosis (p = .03). CONCLUSIONS: These data support that any unusual SH should raise a suspicion of IRBD. Particularly before 1-year of age, it is suggested to first confirm moderate or severe haemophilia and severe IRBD by standard coagulation tests (APTT, PT and fibrinogen), combined with a clotting FXIII assay as first-line investigation. Subsequent assays of coagulation factors should be performed in the case of abnormal values, in second-line investigation.

Impact of inherited bleeding disorders on maternal bleeding and other pregnancy outcomes: A population-based cohort study.

INTRODUCTION: Increasing rate of postpartum haemorrhage (PPH) has been observed between 2003 and 2010 in Canada. Inherited bleeding disorders contribute to the risk of PPH. AIM: To identify the trend in PPH in the last decade, assess the impact of bleeding disorders on pregnancy outcomes and evaluate their coagulation workup during pregnancy. METHODS: We conducted a population-based retrospective cohort study using the Alberta Pregnancy Birth Cohort from 2010 to 2018. We included women with von Willebrand disease (VWD) and haemophilia, identified by previously validated algorithm and matched with controls. Logistic regression was used to compute odds of PPH and other pregnancy outcomes. RESULTS: We identified 311,330 women with a total of 454,400 pregnancies with live births. The rate of PPH did not change significantly from 10.13 per 100 deliveries (95% CI 10.10-10.16) in 2010-10.72 (95% CI 10.69-10.75) in 2018 (p for trend = .35). Women with bleeding disorders were significantly more likely to experience PPH (odds ratio [OR] 2.3; 95% CI 1.5-3.6), antepartum haemorrhage (OR 2.9; 95% CI 1.5-5.9) and red cell transfusion (OR 2.8; 95% CI 1.1-7.0). We observed a nonsignificant rise in the rate of PPH in women with VWD and haemophilia. Only 49.5% pregnancies with bleeding disorders had third trimester coagulation factor levels checked. Higher odds of PPH and antepartum haemorrhage were observed even with factor levels ≥0.50 IU/mL in third trimester. CONCLUSION: Despite comprehensive care in women with bleeding disorders, they are still at higher risk of adverse pregnancy outcomes compared to population controls.

Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review.

OBJECTIVE: Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment. DATA SOURCES: We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles. STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible. METHODS: Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies, we used effect direction tables and summarized results narratively. RESULTS: Twenty-two studies were included for analysis. For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization, and intensive care unit stay, and maternal well-being. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (risk ratio, 0.40; 95% confidence interval, 0.32-0.50) and blood transfusion for bleeding, postpartum hemorrhage, severe postpartum hemorrhage, and mean blood loss. One nonrandomized trial and 7 uncontrolled studies suggest that other postpartum hemorrhage treatment bundles might reduce blood loss and severe postpartum hemorrhage, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative care bundle may reduce severe maternal morbidity (risk ratio, 0.64; 95% confidence interval, 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution. CONCLUSION: The E-MOTIVE intervention improves postpartum hemorrhage-related outcomes among women delivering vaginally, and the California Maternal Quality Care Collaborative bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.

Avacopan for ANCA-associated vasculitis with hypoxic pulmonary haemorrhage.

BACKGROUND AND HYPOTHESIS: Pulmonary haemorrhage with hypoxia caused by ANCA-associated vasculitis (AAV) has a high early mortality. Avacopan, an oral C5a receptor antagonist, is an approved treatment for AAV, but patients with pulmonary haemorrhage requiring invasive pulmonary ventilation support were excluded from the ADVOCATE trial. METHODS: A retrospective, observational, multicentre case series of AAV patients with hypoxic pulmonary haemorrhage, requiring oxygen support or mechanical ventilation, who received avacopan. RESULTS: Eight patients (62.5% female), median age 64 years (range 17-80), seven with kidney involvement, median glomerular filtration rate (GFR) 11 (range 5-99) ml/min per 1.73m2, were followed for a median of 6 months from presentation. Seven were newly diagnosed (87.5%), five were MPO-ANCA and three PR3-ANCA positive. All had hypoxia, four requiring mechanical ventilation (three invasive and one non-invasive). Intensive care unit (ICU) stay for the four patients lasted a median of 9 days (range 6-60). Four received rituximab and cyclophosphamide combination, three rituximab and one cyclophosphamide. Four underwent plasma exchange and one received two months of daily extracorporeal membrane oxygenation (ECMO) therapy. Following the initiation of avacopan after a median of 10 days (range 2-40), pulmonary haemorrhage resolved in all patients, even two who had one month of refractory pulmonary haemorrhage prior to avacopan. Additionally, after one month, the median prednisolone dose was 5 mg/day (range 0-50), with three patients successfully discontinuing steroid use. Two patients suffered serious infections, two discontinued avacopan, one permanently due to a rash and one temporarily after three months due to neutropenia. All patients survived and no re-hospitalization occurred. CONCLUSION: We report the use of avacopan as a component of the treatment for pulmonary haemorrhage with hypoxia in AAV. Despite the life-threatening presentations all patients recovered, but attribution of the positive outcomes to avacopan is limited by the concomitant therapies and retrospective observational design.

A retrospective analysis of postpartum red blood cell transfusions at a tertiary care obstetric centre.

BACKGROUND AND OBJECTIVES: Postpartum anaemia is a prevalent health problem. We aimed to determine the compliance rate for red blood cell (RBC) transfusion indication among postpartum women in a single tertiary care centre in Quebec, Canada. MATERIALS AND METHODS: Retrospective cohort study including all women ≥6 h postpartum who received ≥1 RBC transfusion during their delivery hospitalization between January 2005 and February 2022. We determined our centre's compliance rate by indication as compared to current society guidelines, all published after 2015 (Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis [NATA], Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG]). We then explored predictors of guideline non-compliance and described transfusion practices in our centre. RESULTS: A total of 171 women were included. Our centre's compliance rate was 79.5% (95% confidence interval [CI] 72.7-84.8). Predictors of guideline non-compliance were maternal medical comorbidity or abnormal placentation, both limited by large CIs (odds ratio [OR] 2.26, CI 1.02-4.94, p = 0.04; OR 4.00, CI 1.31-12.06, p = 0.01, respectively). Postpartum haemorrhage was diagnosed among 68% of the cohort, mostly due to uterine atony (73.3%). Mean baseline and nadir haemoglobin were 111 g/L (±18) and 62 g/L (±7.7), respectively. Multiple unit initial transfusion was found in a majority of patients (63.7%). Iron therapy was administered to 51.5% of women in-hospital and 81.9% received an oral iron prescription at discharge. There were no differences in primary or secondary outcomes subsequent to relevant guideline publication. CONCLUSION: Our centre's compliance rate for RBC transfusion indication meets current practice guidelines. Areas for improvement include single-unit initial transfusion protocols and adjuvant iron treatment. Antenatal optimization of haemoglobin and ferritin stores may limit postpartum transfusions.

Routine maternal ABO/Rhesus D blood typing can alert of massive foetomaternal haemorrhage.

BACKGROUND AND OBJECTIVES: Spontaneous massive foetomaternal haemorrhage (SM-FMH) is a rare yet critical condition that poses substantial risk to foetal health and survival. Existing data indicate that many cases may be undiagnosed. The current study aimed to investigate and validate the utility of identifying mixed field red blood cell (RBC) agglutination during maternal blood typing as a diagnostic aid for SM-FMH. MATERIALS AND METHODS: Retrospective analysis of medical records from neonates born at our tertiary, university-affiliated medical centre between 2016 and 2023 was performed. Diagnosis of SM-FMH was based on neonates born with severe anaemia (haematocrit [HCT] <15%) within the first 24 h post-delivery with positive maternal Kleihauer-Betke (KB) test. Maternal ABO/Rhesus D (RhD) blood typing results were scrutinized with the primary objective of assessing the ability to identify dual RBC populations in cases clinically diagnosed with SM-FMH. RESULTS: Among 29,192 neonates studied, a mere 0.02% (5 cases) exhibited severe SM-FMH. Notably, a mixed field RBC agglutination was discerned in 80% (4/5) of these cases. CONCLUSION: This study underscores the significance of detecting mixed field RBC agglutination during antepartum maternal ABO/RhD blood typing as a potential indicator for SM-FMH. Increased awareness among blood bank technology specialists and obstetricians regarding these laboratory findings could prove instrumental in saving foetal lives.

Comparison of scales for the evaluation of aneurysmal subarachnoid haemorrhage: a retrospective cohort study.

BACKGROUND/OBJECTIVES: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening event with major complications. Delayed cerebral infarct (DCI) occurs most frequently 7 days after aSAH and can last for a prolonged period. To determine the most predictive radiological scales in grading subarachnoid or ventricular haemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single-centre retrospective study. METHODS: A 3-year single-centre retrospective cohort study of 230 patients hospitalised for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalised for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Haemorrhage (IVH) score, Graeb score and LeRoux score. RESULTS: Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% of cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval (CI), 0.74-0.85). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79-0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10-1.25). CONCLUSIONS: Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice. CLINICAL RELEVANCE STATEMENT: Better assessment of subarachnoid haemorrhage patients would allow for better prognostication and management of expectations, as well as referral for appropriate services and helping to appropriate use limited critical care resources. KEY POINTS: Aneurysmal subarachnoid haemorrhage is a life-threatening event that causes severe disability and leads to major complications such as delayed cerebral infarction. Accurate assessment of the amount of blood in the subarachnoid spaces on computed tomography with the Hijdra scale can better predict the risk of delayed cerebral infarct. The Hijdra scale could be a good triage tool for subarachnoid haemorrhage patients.

Long-term headache after spontaneous intracerebral haemorrhage.

BACKGROUND: Though headache is commonly observed after stroke and may affect survivors' quality of life, it has rarely been studied after spontaneous intracerebral haemorrhage (ICH). In a cohort of ICH survivors, we assessed the long-term prevalence and determinants of headache. METHODS: We screened consecutive ICH survivors enrolled in the prospective, single-centre Prognosis of Intracerebral Haemorrhage study for headache 1, 3, and 6 years after ICH, according to the International Headache Society's criteria. Depressive and anxiety symptoms severity was measured at 1-year follow-up. Variables associated with the presence of headache 1 year after ICH were analyzed using univariate and multivariable models. RESULTS: Among the 146 patients included in this study, 31 (21%), 25 (19%), and 14 (20%) patients reported headache at 1-, 3-, and 6-year follow-up, respectively. In an age-adjusted model, patients with headache at ICH onset (adjusted odds ratio [aOR] 2.75; 95% CI 1.02-7.42) and previous history of headache (aOR 4.60; 95% CI 1.74-12.1) were associated with headache at 1-year follow-up. Patients with headache were more likely to report depressive and anxiety symptoms at 1-year follow-up (both p < 0.02). CONCLUSIONS: One in five ICH survivors suffered from headache and patients who reported headache at ICH onset were especially at risk.

Risk of subarachnoid haemorrhage reduces with blood pressure values below hypertensive thresholds.

BACKGROUND: Hypertension is a known risk factor for subarachnoid haemorrhage (SAH). The aim of this study was to describe the relationship between blood pressure and SAH using a large cohort study and perform a meta-analysis of the published literature. METHODS: Participants in the UK Biobank were followed up via electronic records until 31 March 2017. Cox proportional hazards models were used to analyse the association between baseline blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP] and MABP [mean arterial blood pressure]) and subsequent aneurysmal SAH. Linearity was assessed by comparing models including and excluding cubic splines. Electronic databases were searched from inception until 11 February 2022 for studies reporting on blood pressure and SAH. RESULTS: A total of 500,598 individuals were included with 539 (0.001%) suffering from aneurysmal SAH. Nonlinear models including cubic splines visually appeared linear between SBP of 110 and 180 mmHg and there was minimal difference in fit between linear and nonlinear models. When values were stratified, those with SBP 120-130 mmHg were at higher risk compared to those with SBP <120 mmHg (hazard ratio [HR] 1.41 [1.02, 1.95]). The meta-analysis demonstrated a similar increased risk of SAH in individuals with SBP 120-130 mmHg relative to those with <120 mmHg (HR 1.41 [1.17, 1.72]). A stepwise increase in risk was also seen at each subsequent threshold (130-140 mmHg: HR 1.85 [1.53, 2.24], 140-160 mmHg: HR 2.16 [1.57, 2.98], 160-180 mmHg: HR 2.81 [1.85, 4.29], >180 mmHg: HR 5.84 [1.94, 17.54]). CONCLUSIONS: The rate of SAH increases linearly with higher SBP in the general population and specifically appears lower in those with SBP <120 mmHg.