STudy to ActivelY WARM trauma patients (STAY WARM): a pilot study assessing feasibility of self-warming blankets in patients requiring a massive hemorrhage protocol activation.

PURPOSE: Massively bleeding trauma patients often arrive to intensive care units hypothermic. Active warming blankets have shown promise in reducing hypothermia in the pre-hospital setting, but less is known about their in-hospital use. The aim of this pilot evaluation was to understand the feasibility of the Ready-Heat® blanket in a level 1 trauma centre to improve the management of hypothermia in massively bleeding trauma patients. METHODS: This was a prospective, observational, feasibility study of 15 patients performed at a single level 1 trauma centre. Patients were eligible for enrollment if they presented to the trauma bay and a massive hemorrhage protocol was activated. Primary outcome measures (feasibility) included: blanket applied to the patient; temperature recording in the trauma bay, and next phase or final phase of care; and blanket remaining on patient upon arrival to the subsequent phase of care.Secondary outcome measures (safety) included skin irritation and cold discomfort. Use of the Ready-Heat® blanket was considered feasible if 10 of 15 patients met all four criteria for feasibility. RESULTS: The Ready-Heat® blanket was placed on all patients with mean time to blanket application of 24 (± 13.4) minutes. Thirteen patients (86.7%) met all four criteria for feasibility. Initial challenges were identified in the first five patients including proper blanket application, keeping the blanket on the patient through subsequent phases of care, and failure to obtain temperature recordings. CONCLUSION: The Ready-Heat® blanket proves feasible for this patient population. A larger study focusing on hypothermia prevention and treatment is warranted. TRIAL REGISTRATION NUMBER: NCT04399902. DATE OF REGISTRATION: May 22, 2020.

Healthcare provider's perceptions of bleeding in patients with acute leukaemia undergoing induction chemotherapy: A qualitative study.

BACKGROUND: Bleeding is a primary outcome for many transfusion-related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi-step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients. STUDY DESIGN AND METHODS: Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used. RESULTS: HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding. DISCUSSION: Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients.

Reducing blood product wastage through the inter-hospital redistribution of near-outdate inventory.

BACKGROUND: Hospital transfusion services order blood products to satisfy orders and maintain inventory levels during unexpected periods of increased blood demand. Surplus inventory may outdate before being allocated to a recipient. Blood product outdating is the largest contributor to blood wastage. STUDY DESIGN: A province-wide redistribution program was designed and implemented to redistribute near-outdate plasma protein and related blood products from low-usage to high-usage hospitals. Program operations and details are described in this paper. Two transport container configurations were designed and validated for transport of all blood products. A cost-analysis was performed to determine the effectiveness of this redistribution program. RESULTS: A total of 130 hospital transfusion services contributed at least one near-outdate blood product for redistribution between January 2012 and March 2020. These services redistributed 15,499 products through 3412 shipments, preventing the outdating of $17,570,700 CAD worth of product. Program costs were $14,900 for shipping and $30,000 for staffing. Failed time limits or non-compliance with packing configurations resulted in $388,200 worth of blood products (97 shipments containing 816 products) being discarded. Courier transport delays was the most common reason (42/97; 43%) for transport failure. CONCLUSION: Redistributing near-outdate blood products between hospitals is a feasible solution to minimize outdating. Despite heterogeneity of Canadian blood product inventory, all products (each with unique storage and transport requirements) were successfully redistributed in one of two validated and simple containers. Total operation costs of this program were small in comparison to the $17.6 million in savings associated with preventing the discard of outdated products.

Improving appropriate use of intravenous albumin: results of a single-centre audit and multifaceted intervention.

BACKGROUND: Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence. AIM: To reduce unnecessary transfusion of albumin. INTERVENTIONS: Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage. IMPLEMENTATION AND EVALUATION: Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures. RESULTS: Appropriate albumin usage based on indication increased from 30% to 50% (p<0.0001). There was significantly less overall albumin usage in the post-intervention period compared with the pre-intervention period (negative coefficient, p<0.0001), driven by a major reduction in the utilisation of the 5% formulation (p<0.0001). Overall albumin usage was significantly lower in the post-intervention period, decreasing from 800 to 450 vials per month. The intervention resulted in significantly less wastage (negative coefficient, p=0.017). Mortality, length of stay and new starts on kidney replacement therapy remained constant throughout the study period. CONCLUSION: Improved prescribing of albumin was achieved with a multifaceted approach. Substantial and sustained reductions in usage were achieved without negatively impacting patient-important outcomes. The estimated annual savings for the purchase cost of albumin was CAN $300 000. We provide a structured process for other organisations to optimise their use of albumin.

Proceedings of the immune thrombocytopenia summit: new concepts in mechanisms, diagnosis, and management.

The inaugural McMaster Immune Thrombocytopenia (ITP) Summit was held virually in 2021. The objectives of the Summit were to recognize the difficulties in establishing the diagnosis of ITP and to understand gaps in current knowledge of ITP mechanisms that might lead to better diagnostic approaches and treatments. The half-day program consisted of virtual educational sessions targeting clinicians and basic scientists. The planning committee chose 8 topics to review that would cover current knowledge and inform future research priorities. In this report, we summarized the presentations delivered at the 2021 McMaster ITP Summit and the discussions. Based on the information presented at the Summit, the following research priorities were identified: 1) investigation of platelet production as a target for ITP treatments; 2) characterization of antigen processing and antigen presentation on platelets; 3) interaction between megakaryocytes and the immune system; 4) the role for ITP gene panels; 5) the need for better methods for platelet antibody testing; 6) the role of prediction models for diagnosis and prognosis; 7) new treatment strategies, including intensification of initial therapy; and 8) personalized treatment algorithms.

Unique features of vaccine-induced immune thrombotic thrombocytopenia; a new anti-platelet factor 4 antibody-mediated disorder.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a highly prothrombotic disorder caused by anti-PF4 antibodies that activate platelets and neutrophils, leading to thrombosis. Heparin-induced thrombocytopenia (HIT) is a related anti-PF4 mediated disorder, with similar pathophysiology and clinical manifestations but different triggers (i.e., heparin vs adenoviral vector vaccine). Clinically, both HIT and VITT typically present with thrombocytopenia and thrombosis, although the risk of thrombosis is significantly higher in VITT, and the thromboses occur in unusual anatomical sites (e.g., cerebral venous sinus thrombosis and hepatic vein thrombosis). The diagnostic accuracy of available laboratory testing differs between HIT and VITT; for VITT, ELISAs have better specificity compared to HIT and platelet activation assays require the addition of PF4. Treatment of VITT and HIT is anticoagulation non-heparin anticoagulants; however, heparin may be considered for VITT if no other option is available.

Vaccine-induced immune thrombotic thrombocytopenia: Updates in pathobiology and diagnosis.

Coronavirus disease 2019 (COVID-19) is a viral respiratory infection caused by the severe acute respiratory syndrome virus (SARS-CoV-2). Vaccines that protect against SARS-CoV-2 infection have been widely employed to reduce the incidence of symptomatic and severe disease. However, adenovirus-based SARS-CoV-2 vaccines can cause a rare, thrombotic disorder termed vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT often develops in the first 5 to 30 days following vaccination and is characterized by thrombocytopenia and thrombosis in unusual locations (e.g., cerebral venous sinus thrombosis). The diagnosis is confirmed by testing for anti-PF4 antibodies, as these antibodies are capable of platelet activation without any cofactor. It can be clinically challenging to differentiate VITT from a similar disorder called heparin-induced thrombocytopenia (HIT), since heparin is commonly used in hospitalized patients. VITT and HIT have similar pathobiology and clinical manifestations but important differences in testing including the need for PF4-enhanced functional assays and the poor reliability of rapid immunoassays for the detection of anti-platelet factor 4 (PF4) antibodies. In this review we summarize the epidemiology of VITT; highlight similarities and differences between HIT and VITT; and provide an update on the clinical diagnosis of VITT.

Digital Microfluidic Hemagglutination Assays for Blood Typing, Donor Compatibility Testing, and Hematocrit Analysis.

BACKGROUND: Blood typing, donor compatibility testing, and hematocrit analysis are common tests that are important in many clinical applications, including those found in high-stakes settings such as the trauma center. These tests are typically performed in centralized laboratories with sample batching; the minutes that are lost in this mode can lead to adverse outcomes, especially for critical-care patients. As a step toward providing rapid results at the bedside, we developed a point-of-care hemagglutination system relying on digital microfluidics (DMF) and a unique, automated readout tool, droplet agglutination assessment using digital microfluidics (DAAD). METHODS: ABO and Rhesus blood grouping, donor crossmatching, and hematocrit assays were developed on a portable DMF platform that allowed for automated sample processing. The result of each assay could be determined by eye or automatically with the DAAD imaging tool. RESULTS: DMF-DAAD was applied to 109 samples collected from different sources (including commercial samples, pinpricks from volunteers, and a hospital blood bank), with perfect fidelity to gold-standard results. Some of these tests were carried out by a nonexpert in a hospital trauma center. Proof-of-concept results were also collected from smaller sample sets for donor compatibility testing and hematocrit analysis. CONCLUSION: DMF-DAAD shows promise for delivering rapid, reliable results in a format well suited for a trauma center and other settings where every minute counts.

Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial.

BACKGROUND: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection. METHODS: CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600). DISCUSSION: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification. TRIAL REGISTRATION: Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.

Multicenter observational study evaluating the impact of platelet transport bags on product wastage.

BACKGROUND: Platelets are the most commonly discarded blood product in Canada, with the most common cause of in-date product loss being improper storage. Transport containers to maintain temperature and extend acceptable return time may represent a method to reduce wastage. The objective of this study was to evaluate the impact of a validated Platelet Transport Bag (PTB) on platelet wastage. STUDY DESIGN AND METHODS: Thirty-six hospitals with the highest platelet discards were invited to participate in a before-after observational study. Hospitals were instructed to utilize a validated 4-h PTB for clinical situations where immediate transfusion was not planned. Five hospitals audited in-date platelet discards from July 2018 to November 2019 to characterize wastage causes. In-date platelet discard data 12 months before and after the start date for each site were analyzed to determine changes in wastage. RESULTS: Of 36 hospital sites, 16 agreed to participate. Pre- and postdiscards were 277 and 301, respectively, for all sites combined. There were no significant before-after change in wastage rate (+0.05%, p = .51). Fifty discards were included in the detailed audit; the most common reasons were return to the blood bank after more than 60 min outside a PTB (n = 17, 34%) and return in a red cell cooler (n = 10, 20%). CONCLUSION: Implementation of PTB did not improve wastage. Common causes of in-date discards were return after 1 h outside of a PTB and placement in a red cell cooler in error. Further research is required to investigate potential strategies to mitigate in-date platelet wastage.