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BACKGROUND: Most studies describing traumatic coagulopathy have used data from patient cohorts with an average age of between 35 and 45 years. The last 10 years has seen a steep increase in the number of patients admitted with significant injury and bleeding who are older than the age of 65 years. Many coagulation protein levels alter significantly with normal aging, and it is possible that traumatic coagulopathy has a different signature with age. OBJECTIVES: The aim of this study was to report the coagulation profiles, including standard and extended laboratory, as well as viscoelastic hemostatic assays, stratified according to age to explore age-related differences in hemostatic capability. METHODS: In total, 1576 patients were analyzed from 6 European level 1 trauma centers. RESULTS: As age increased, there was evidence of higher fibrinogen, greater thrombin generation, greater clotting factor consumption, and greater activation of fibrinolysis. Despite this, shock and severe injury led to the same pattern of changes within age groups: lower procoagulant factors (including fibrinogen), increased fibrinolysis, and higher levels of activated protein C. Thromboelastography and rotational thromboelastometry tests detected traumatic coagulopathy with prolongation of R/clotting time and reductions in clot amplitudes in each age cohort. Advancing age strongly correlated with higher fibrinogen levels and greater fibrinolysis. CONCLUSION: Age-related coagulation changes are evident in injured patients. Broadly, similar patterns of coagulation abnormalities are seen across age groups following severe injury/shock, but thresholds for single clotting factors differ. Age-related differences may need to be considered when clinical treatments (eg, transfusion therapy) are indicated.

Objectives We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hospital in our regional network of 7 hospitals. Methods Consecutive hospitalised patients with haematological malignancy and SARS-CoV-2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. Results 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS-CoV-2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test). Conclusions Mortality rates in patients with haematological malignancy and SARS-CoV-2 infection in hospital are high supporting measures to minimise the risk of infection in this population.

© 2020 The Authors. Transfusion published by Wiley Periodicals LLC. on behalf of AABB. Background: The majority of potentially preventable deaths in trauma are due to uncontrolled hemorrhage and occur early after injury. How major bleeding is defined is integral to early identification and treatment of this group of high-risk patients. However, there is no consensus on a definition of major bleeding in trauma. The aim of this Delphi study was to develop a consensus definition for research, with transfusion used as a surrogate marker of bleeding. Study Design and Methods: Trauma experts from three international groups were invited to take part in an online Delphi survey. Over the course of four rounds, the group developed a number of definitions of major bleeding and reached consensus on a new definition. Results: Forty-four trauma experts agreed to become members of the Delphi panel, and 30 of 44 (68%) completed all four rounds. The panel agreed to exclude the historical massive transfusion definition (≥10 units of red blood cells within 24 hours). Consensus was reached on a new definition for use in clinical research: 4 or more units of any blood component within 2 hours of injury. Conclusion: This Delphi process has yielded a pragmatic transfusion-based definition of major bleeding. The consensus definition differs from historical definitions: a shorter time frame to reflect the acuity of bleeding, and multiple blood components in keeping with a balanced approach to resuscitation. The definition developed may be best suited to mature trauma systems (reflecting the demographics of the expert panel), and could be used to guide registry data recording and to characterize patients at risk of major bleeding.

Henna Wong,1,2 Nicola Lovett,3 Nicola Curry,1 Ku Shah,2 Simon J Stanworth1,2,4 1Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, 2Radcliffe Department of Medicine, University of Oxford, Oxford BRC Haematology Theme, 3Department of Geratology, Oxford University Hospitals NHS Foundation Trust, 4Department of Haematology, NHS Blood and Transplant, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK Abstract: The ageing population has resulted in a change in the demographics of trauma, and older adult trauma now accounts for a growing number of trauma admissions. The management of older adult trauma can be particularly challenging, and exhibits differences to that of the younger age groups affected by trauma. Frailty syndromes are closely related with falls, which are the leading cause of major trauma in older adults. Comorbid disease and antithrombotic use are more common in the older population. Physiological changes that occur with ageing can alter the expected clinical presentation of older persons after injury and their susceptibility to injury. Following major trauma, definitive control of hemorrhage remains essential for improving outcomes. In the initial assessment of an injured patient, it is important to consider whether the patient is taking anticoagulants or antiplatelets and if measures to promote hemostasis such as reversal are indicated. After hemostasis is achieved and bleeding has stopped, longer-term decisions to recommence antithrombotic agents can be challenging, especially in older people. In this review, we discuss one aspect of management for the older trauma patients in greater detail, that is, acute and longer-term management of antithrombotic therapy. As we consider the health needs of an ageing population, rise in elderly trauma and increasing use of antithrombotic therapy, the need for research in this area becomes more pressing to establish best practice and evidence-based care. Keywords: injury, elderly, anticoagulation, antiplatelet, antithrombotic

Objectives: To determine whether it was feasible to use a haemorrhage assessment tool (HAT) within a trauma trial and whether the data obtained could differentiate patients who had achieved haemostasis. Background: Major haemorrhage is one of the leading causes of death worldwide, affecting 40% of trauma patients. Clinical trials evaluating haemostatic interventions often use transfusion outcomes as a primary endpoint. Transfusion is highly dependent on local practice, limiting its reliability as a robust, transferable endpoint. Methods: A five‐point HAT questionnaire was applied to participants enrolled into the EFIT‐1 trial. This RCT evaluated the feasibility of administering a 6 g fibrinogen concentrate to patients with severe trauma haemorrhage. Results: Of participants, 98% completed a HAT; 75% participants had ‘achieved haemostasis’ at the time of tool completion, as determined by clinical acumen alone. HAT scores were able to differentiate which participants required transfusion after 3 h. Of participants, 56% were transfused red blood cells when they scored 0–2, compared to 17% with HAT scores between 3 and 5. Conclusion: This study has confirmed the feasibility of using a HAT during the emergency care of patients suffering trauma haemorrhage, and future studies should be conducted to determine its value as an endpoint in haemostasis studies.

Summary Background The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments. Methods The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed. Findings Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p

To promote trainee-led clinical research and audit in non-malignant haematology. Haematology Specialty Trainee Audit and Research (HaemSTAR) is a national network of haematology trainees. HaemSTAR is a new initiative, conceived in 2016 and supported by the National Institution for Health Research (

Purpose To evaluate the safety (risk of infection) and efficacy (transfusion requirements, changes in haemoglobin (Hb)) of iron therapy in adult intensive care unit (ICU) patients. Materials and methods We systematically searched seven databases for all relevant studies until January 2018 and included randomized (RCT) studies comparing iron, by any route, with placebo/no iron. Results 805 participants from 6 RCTs were included. Iron therapy, by any route, did not decrease the risk of requirement for a red blood cell (RBC) transfusion (Risk ratio (RR) 0.91, 95% CI 0.80 to 1.04, p = 0.15) or mean number of RBCs transfused per participant (mean difference (MD) -0.30, 95% CI -0.68 to 0.07, p = 0.15). Iron therapy did increase mean Hb concentration (MD 0.31 g/dL, 95% CI 0.04 to 0.59, p = 0.03). There was no difference in infection (RR 0.95, 95% CI 0.79 to 1.19, p = 0.44). Trial Sequential Analysis suggests that the required participant numbers to detect or reject a clinically important effect of iron therapy on transfusion requirements or infection in ICU patients has not yet been reached. Conclusion Iron therapy results in a modest increase in Hb. The current evidence is inadequate to exclude an important effect on transfusion requirements or infection.

Summary Background Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The objective of this review is to assess the effects and safety of blood product transfusion strategies started in the first 24 hours after injury for trauma patients of all ages with major bleeding.

Purpose of review Death from uncontrolled haemorrhage is one of the leading causes of trauma-related mortality and is potentially preventable. Advances in understanding the mechanisms of trauma-induced coagulopathy (TIC) have focused attention on the role of blood products and procoagulants in mitigating the sequelae of TIC and how these therapies can be improved. Recent findings A host of preclinical and clinical studies have evaluated blood product availability and efficacy in trauma. Recently published randomized controlled trials have investigated the ratio of platelet:plasma:red cell transfusion and the role of early cryoprecipitate in trauma. Demand for readily available plasma has led to changes particularly in the use of thawed group A plasma. Furthermore, ex-vivo and early clinical work has demonstrated variations in the haemostatic activity of different plasma, platelet and whole blood products. A number of multicentre trials are in progress aiming to answer key questions regarding tranexamic acid, procoagulant factor and fibrinogen concentrates and their effect on trauma outcomes. Summary There are promising results from ex-vivo studies in manufacturing and storage of blood products to optimize haemostatic activity and availability, particularly with alternative plasma and platelet products and whole blood. There is an urgent need for these products needs to be tested prospectively.

Recurrence following initial treatment for venous thromboembolism is a significant cause of morbidity and mortality. Balancing the risks of recurrence against the risks of long-term anticoagulation is essential for optimizing patient outcomes.

Leukemia-associated chimeric oncoproteins often act as transcriptional repressors, targeting promoters of master genes involved in hematopoiesis. We show that CRABPI (encoding cellular retinoic acid binding protein I) is a target of PLZF, which is fused to RARα by the t(11;17)(q23;q21) translocation associated with retinoic acid (RA)-resistant acute promyelocytic leukemia (APL). PLZF represses the CRABPI locus through propagation of chromatin condensation from a remote intronic binding element culminating in silencing of the promoter. Although the canonical, PLZF-RARα oncoprotein has no impact on PLZF-mediated repression, the reciprocal translocation product RARα-PLZF binds to this remote binding site, recruiting p300, inducing promoter hypomethylation and CRABPI gene up-regulation. In line with these observations, RA-resistant murine PLZF/RARα+RARα/PLZF APL blasts express much higher levels of CRABPI than standard RA-sensitive PML/RARα APL. RARα-PLZF confers RA resistance to a retinoid-sensitive acute myeloid leukemia (AML) cell line in a CRABPI-dependent fashion. This study supports an active role for PLZF and RARα-PLZF in leukemogenesis, identifies up-regulation of CRABPI as a mechanism contributing to retinoid resistance, and reveals the ability of the reciprocal fusion gene products to mediate distinct epigenetic effects contributing to the leukemic phenotype.