Impact of antithrombotic agents on outcomes in patients requiring surgery for chronic subdural haematoma: a systematic review and meta-analysis.

A chronic subdural haematoma (CSDH) is a collection of aged blood between the dura and the brain, typically treated with surgical evacuation. Many patients with CSDH have comorbidities requiring the use of antithrombotic medications. The optimal management of these medications in the context of CSDH remains unknown, as the risk of recurrence must be carefully weighed against the risk of vaso-occlusive events. To better understand these risks and inform the development of clinical practice guidelines, we conducted a systematic review and meta-analysis. A systematic review was conducted in accordance with the PRISMA guidelines, searching Medline and Embase databases. The study was registered with PROSPERO (CRD42023397061). A total of 44 studies were included, encompassing 1 prospective cohort study and 43 retrospective cohort studies. Pooled odds ratios (ORs) were calculated for CSDH recurrence and vaso-occlusive events in patients taking anticoagulant or antiplatelet medications compared to patients not receiving antithrombotic therapy. GRADE was used to assess the quality of evidence. In patients on anticoagulant therapy at CSDH diagnosis, the pooled OR for CSDH recurrence was 1.41 (95% CI 1.11 to 1.79; I2 = 28%). For patients on antiplatelet therapy, the pooled OR was 1.31 (95% CI 1.08 to 1.58; I2 = 32%). Patients taking antithrombotic medications had a significantly higher risk of vaso-occlusive events, with a pooled OR of 3.74 (95% CI 2.12 to 6.60; I2 = 0%). There was insufficient evidence to assess the impact of time to recommence antithrombotic medication on CSDH outcomes. We found that baseline antithrombotic use is associated with the risk of CSDH recurrence and vaso-occlusive events following surgical evacuation. The evidence base is of low quality, and decisions regarding antithrombotic therapy should be individualised for each patient. Further high-quality, prospective studies or registry-based designs are needed to better inform clinical decision-making and establish evidence-based guidelines.

Association of red blood cells and plasma transfusion versus red blood cell transfusion only with survival for treatment of major traumatic hemorrhage in prehospital setting in England: a multicenter study.

BACKGROUND: In-hospital acute resuscitation in trauma has evolved toward early and balanced transfusion resuscitation with red blood cells (RBC) and plasma being transfused in equal ratios. Being able to deliver this ratio in prehospital environments is a challenge. A combined component, like leukocyte-depleted red cell and plasma (RCP), could facilitate early prehospital resuscitation with RBC and plasma, while at the same time improving logistics for the team. However, there is limited evidence on the clinical benefits of RCP. OBJECTIVE: To compare prehospital transfusion of combined RCP versus RBC alone or RBC and plasma separately (RBC + P) on mortality in trauma bleeding patients. METHODS: Data were collected prospectively on patients who received prehospital transfusion (RBC + thawed plasma/Lyoplas or RCP) for traumatic hemorrhage from six prehospital services in England (2018-2020). Retrospective data on patients who transfused RBC from 2015 to 2018 were included for comparison. The association between transfusion arms and 24-h and 30-day mortality, adjusting for age, injury mechanism, age, prehospital heart rate and blood pressure, was evaluated using generalized estimating equations. RESULTS: Out of 970 recruited patients, 909 fulfilled the study criteria (RBC + P = 391, RCP = 295, RBC = 223). RBC + P patients were older (mean age 42 vs 35 years for RCP and RBC), and 80% had a blunt injury (RCP = 52%, RBC = 56%). RCP and RBC + P were associated with lower odds of death at 24-h, compared to RBC alone (adjusted odds ratio [aOR] 0.69 [95%CI: 0.52; 0.92] and 0.60 [95%CI: 0.32; 1.13], respectively). The lower odds of death for RBC + P and RCP vs RBC were driven by penetrating injury (aOR 0.22 [95%CI: 0.10; 0.53] and 0.39 [95%CI: 0.20; 0.76], respectively). There was no association between RCP or RBC + P with 30-day survival vs RBC. CONCLUSION: Prehospital plasma transfusion for penetrating injury was associated with lower odds of death at 24-h compared to RBC alone. Large trials are needed to confirm these findings.

A single-centre review of iatrogenic anaemia in adult intensive care.

OBJECTIVES: (a) To quantify the volume of diagnostic blood loss (DBL) and evaluate its impact on intensive care unit (ICU) patients, (b) examine the correlation between severity of disease and DBL and (c) identify potentially vulnerable patient subgroups. BACKGROUND: Iatrogenic anaemia is an important problem amongst ICU patients, with significant daily DBL. METHODS: A single-centre observational cohort study was conducted at St George's Hospital, London, cardiac and general ICU. Forty patients were included in the study. Variables measured were volume of blood collected and discarded on a daily basis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, frequency of phlebotomy, haemoglobin concentration before and after admission to ICU, reason for admission and complications developed in ICU. RESULTS: Mean (SD) total volume drawn per patient per day over 4 days was 86.3 mL (19.58). Nearly 30% of the total blood taken was discarded. There was a strong positive correlation between patients admitted because of sepsis and volume of DBL (P < .01), APACHE II score and volume taken (P = .01), patients who developed respiratory failure requiring ventilation and volume taken (P < .01) and patients who had received a blood transfusion and volume taken (P < .01). Haemoglobin concentration on discharge was negatively associated with DBL volume (P < .01). CONCLUSION: High volumes of blood were taken and discarded from the study population, possibly reflecting the fact that there are no guidelines for ICU staff in terms of the amount of blood that needs to be withdrawn in order to "prime" access lines.

A mixed methodology, non-interventional study to evaluate the use of direct oral anticoagulants in UK clinical practice for patients with a first stroke associated with non-valvular atrial fibrillation: study protocol.

BACKGROUND: Treatment with anticoagulants, including direct oral anticoagulants (DOACs), should be considered for patients diagnosed with atrial fibrillation (AF) deemed at risk of ischaemic stroke. There are limited real world data related to the characteristics of patients with non-valvular AF who were not taking anticoagulants at the time of first ischaemic stroke and their subsequent DOAC treatment for the secondary prevention of stroke. Furthermore, little is known about patient adherence and experiences of DOAC treatment, especially for patients with non-valvular AF receiving DOAC therapy for the secondary prevention of stroke. METHODS: This is a UK mixed methodology, non-interventional study, involving retrospective and prospective medical record reviews and a prospective patient survey, in progress in six UK National Health Service secondary/tertiary care centres. The study comprises two groups of patients. Group 1 will include 300 eligible consenting patients with a first ischaemic stroke associated with non-valvular AF untreated with anticoagulants in the 12 months prior to stroke. Group 2 will include a subgroup of 150 patients from Group 1 initiated on one of the DOACs targeting activated Factor X (n = 50 on apixaban, n = 50 on edoxaban and n = 50 on rivaroxaban). The primary endpoint of the study is the CHA2DS2-VASc Risk Score prior to initiation of anticoagulation for patients included in Group 1. Secondary endpoints to be evaluated in Group 1 include patient demographics, clinical characteristics, relevant medical history, anticoagulant therapy initiated for secondary prevention of stroke, and relevant concomitant medication. Secondary endpoints to be evaluated in Group 2 include the time between stroke and DOAC initiation; prescribing of DOACs, other anticoagulants and concomitant medication; clinical assessments and hospital resource use; patient reported outcome measures, including the Morisky Medication Adherence Scale questionnaire and the Treatment Satisfaction Questionnaire for Medication. DISCUSSION: This mixed methodology study will provide new real world insights into the characteristics and management pathways and patient-reported experiences of this important group of patients. It is anticipated that the results of this study will provide the medical community and patients with important information to inform clinical decision-making and help facilitate meaningful improvements in the care of patients with non-valvular AF.

Lower uterine segment placental thickness in women with abnormally invasive placenta.

INTRODUCTION: Ultrasound signs of abnormal placental invasion are subjective in nature. We tested the hypothesis that placental thickness in the lower uterine segment is increased when there is abnormally invasive placenta (AIP) in women with a low-lying placenta. MATERIAL AND METHODS: Retrospective analysis of data of placental thickness in women with ultrasound evidence of major placenta previa or a low-lying anterior placenta was done. The diagnosis of AIP was confirmed both intraoperatively and on histopathology for those managed by partial myometrial excision with uterine conservation or by hysterectomy. RESULTS: In all, 131 records were available for analysis after exclusion of 33 cases due to unsuitable images and eight cases without pregnancy outcomes. The diagnosis of AIP was confirmed in 28 (21.4%) of the 131 cases. The lower segment placental thickness was significantly higher in women with AIP (median = 50.3 mm, IQR: 42.7-64.3) than in those with normal placentation (median = 30.9 mm, IQR: 22.9-42.2, P < 0.001). Logistic regression analysis showed that previous cesarean section and placental thickness on ultrasound were independent predictors for AIP. CONCLUSIONS: Lower uterine segment placental thickness is increased in women with AIP compared with those with noninvasive placentation. This association constitutes a pragmatic objective sign and may be of clinical value in improving prenatal detection of AIP in women with placental implantation in the lower uterine segment. Prospective studies are necessary to ascertain lower segment placental thickness as a predictor for AIP.

Monitoring heparin anticoagulation in the acute phase response.

The anticoagulant effect of unfractionated heparin (UFH) is monitored using the activated partial thromboplastin time (APTT). An APTT of 1.5-2.5 times the control is usually taken as the therapeutic range and assumed to reflect an anti-activated factor X (anti-Xa) level of 0.35-0.7 u/ml. However, in some cases, despite administration of sufficient heparin to achieve a therapeutic anti-Xa assay level, the APTT remains sub-therapeutic. This 'apparent heparin resistance' is commonly due to high levels of factor VIII (FVIII). In these situations, the anti-Xa is usually preferred for monitoring in order to avoid, what might be, dangerously high levels of heparin. We hypothesized that at high FVIII levels, the heparin resistance encountered may be genuine rather than apparent and that higher doses of heparin may indeed be needed for an equivalent anticoagulant effect. The relationship between heparin level, APTT and anticoagulant effect at different FVIII concentrations was determined using thrombelastography and the thrombin generation assay. Thromboelastographic and thrombin generation parameters concurred with APTT, demonstrating a genuine heparin resistance in the presence of high FVIII levels. This suggests that APTT may be a more accurate measure of anticoagulant effect in vivo than anti-Xa.

The practicalities and barriers of using TEG6s in code red traumas: an observational study in one London major trauma centre.

OBJECTIVE: Trauma induced coagulopathy is a disorder of the coagulation pathway that occurs following major trauma. "Code red trauma" require massive hemorrhage protocol activation. The aim was to qualitatively establish the reasons TEG is not currently utilized and the ongoing practicalities in performing a TEG sample for trauma-related massive hemorrhage. METHODS: A pilot study was performed using a TEG6s machine within one central London Major Trauma Centre's resuscitation department. Staff were asked to run a TEG sample on any "code red" patient who attended during the trial. Staff were given questionnaires both before and after the trial to assess the knowledge around TEG. RESULTS: A TEG sample was performed in 75% of the sixteen "code red traumas," with one sample being unsuccessful. Only one patient had their blood component management altered due to the TEG result with only 50% of consultants and registrars surveyed feeling confident in interpreting TEG results. CONCLUSION: TEG6s samples can be run within the resuscitation department in a "code red trauma." However, there is a significant lack of knowledge relating to TEG within the emergency department which is likely to hinder its impact on personalized blood component management. More research is required in how to provide appropriate education in a busy setting to enable TEG to be utilized appropriately.

Ferritin and iron studies in anaemia and chronic disease.

Anaemia is a condition in which the number of red cells necessary to meet the body's physiological requirements is insufficient. Iron deficiency anaemia and the anaemia of chronic disease are the two most common causes of anaemia worldwide;1 iron homeostasis plays a pivotal role in the pathogenesis of both diseases. An understanding of how iron studies can be used to distinguish between these diseases is therefore essential not only for diagnosis but also in guiding management. This review will primarily focus on iron deficiency anaemia and anaemia of chronic disease; however, iron overload in anaemia will also be briefly discussed.

Management of rivaroxaban in relation to bodyweight and body mass index.

Being overweight or obese is associated with a higher individual risk of venous thromboembolism and poorer postprocedural outcomes after hip or knee replacement surgery. In addition, there is evidence that obesity represents a significant driving factor for the current and projected prevalence of atrial fibrillation. Rivaroxaban and other direct oral anticoagulants offer fixed-dose regimens for these indications. They do not require therapeutic drug monitoring or dose adjustment according to the weight of the patient. However, primary care physicians seem to be hesitant to accept the concept of a fixed-dose regimen for patients at extremes of weight, perhaps because of familiarity with weight-based dosing of other drugs including low molecular weight heparins. The main concerns related to unadjusted dosing are increased exposure in underweight patients leading to a risk of excessive bleeding and conversely to underanticoagulation of overweight patients. Rivaroxaban has shown similar efficacy and a similar or better safety profile compared with standard treatment for several venous and arterial indications, including venous thromboembolism, nonvalvular atrial fibrillation, and acute coronary syndrome. Prespecified subgroup analyses of patients stratified by weight or body mass index demonstrated outcomes that were consistent with the overall analysis and within each weight and body mass index group. The results suggest that standard-dose rivaroxaban can be safely prescribed in adult patients of all weights.

Factor X deficiency.

Factor X is one of the vitamin K-dependent serine proteases. It plays a crucial role in the coagulation cascade, as the first enzyme in the common pathway of thrombus formation. The gene for factor X maps to the long arm of chromosome 13, approximately 2.8 kb downstream of the factor VII gene. The gene consists of eight exons, each of which encodes a specific functional domain within the protein. Both the gene structure and the amino acid sequence show homology to other vitamin K-dependent clotting factors, suggesting their origin in a common ancestral protein. Factor X deficiency is one of the rarest of the inherited coagulation disorders. Inheritance is in an autosomal recessive manner. The clinical phenotype is of a variable bleeding tendency. Homozygous factor X deficiency has an incidence of 1:1,000,000 in the general population. Heterozygotes are often clinically asymptomatic. Acquired factor X deficiency is rare, but when it occurs it is usually in association with amyloidosis. Treatment of factor X deficiency involves replacement of the protein with either fresh frozen plasma or prothrombin complex concentrates, although the latter should be used with caution as infusion may be associated with an increased risk of thrombosis.

Case 39: an elderly man with red cell aplasia.

An elderly man presented with a macrocytic anemia with severe reticulocytopenia. The observation of trilineage dysplasia in addition to red cell aplasia led to a diagnosis.