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Although high titers of neutralizing Abs in human serum are associated with protection from reinfection by SARS-CoV-2, there is considerable heterogeneity in human serum-neutralizing Abs against SARS-CoV-2 during convalescence between individuals. Standard human serum live virus neutralization assays require inactivation of serum/plasma prior to testing. In this study, we report that the SARS-CoV-2 neutralization titers of human convalescent sera were relatively consistent across all disease states except for severe COVID-19, which yielded significantly higher neutralization titers. Furthermore, we show that heat inactivation of human serum significantly lowered neutralization activity in a live virus SARS-CoV-2 neutralization assay. Heat inactivation of human convalescent serum was shown to inactivate complement proteins, and the contribution of complement in SARS-CoV-2 neutralization was often >50% of the neutralizing activity of human sera without heat inactivation and could account for neutralizing activity when standard titers were zero after heat inactivation. This effect was also observed in COVID-19 vaccinees and could be abolished in individuals who were undergoing treatment with therapeutic anti-complement Abs. Complement activity was mainly dependent on the classical pathway with little contributions from mannose-binding lectin and alternative pathways. Our study demonstrates the importance of the complement pathway in significantly increasing viral neutralization activity against SARS-CoV-2 in spike seropositive individuals.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Via Clássica do Complemento , Testes de Neutralização , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , COVID-19/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Via Clássica do Complemento/imunologia , Vacinas contra COVID-19/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Convalescença , Idoso , Proteínas do Sistema Complemento/imunologiaRESUMO
BACKGROUND AND OBJECTIVES: By optimizing erythropoiesis, patient blood management (PBM) programmes can reduce transfusions, lower mortality and provide cost-effective care. While definitions of anaemia have historically varied by sex, for the purposes of PBM, anaemia is defined as a haemoglobin <130 g/L. Our objective was to describe whether perioperative anaemia and transfusion rates in the PBM setting vary by sex. MATERIALS AND METHODS: We conducted a retrospective study of the Ontario Nurse Transfusion Coordinators Program (ONTraC) database from 2018 to 2022. ONTraC collects data from 25 Ontario hospitals which together account for >70% of Ontario's provincial blood use (~400,000 units per year). We collected data on patients undergoing elective isolated coronary artery bypass graft surgery (CABG), open heart valve replacement, CABG plus valve replacement, single-knee arthroplasty and single-hip arthroplasty. RESULTS: From 2018 to 2022, 17,700 patients were included in the ONTraC program; 47% were females (N = 8376). Across almost all years and procedures, females were found to have a significantly lower pre-operative, nadir and discharge haemoglobin as compared with males, irrespective of PBM interventions. Transfusion rates were significantly higher for females; this was most pronounced in cardiac surgery. CONCLUSION: Females experienced more perioperative anaemia and higher transfusion rates. Historic sex-specific definitions of anaemia may contribute to a greater tolerance of anaemia in females. Prioritizing females for multimodal PBM and consistently achieving a pre-operative haemoglobin >130 g/L may reduce the amount of red blood cell (RBC) transfusions that female patients receive.
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Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere-winter (December-February); spring (March-May); summer (June-August); autumn (September-November) and Southern Hemisphere-winter (June-August); spring (September-November); summer (December-February); autumn (March-May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%-31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization.
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Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal thrombotic microangiopathy caused by autoantibody-mediated severe deficiency of ADAMTS13. Standardized definitions of response, exacerbation, remission, and relapse were initially proposed in 2003 and modified by the International Working Group for TTP in 2017. These definitions, which have been widely used in clinical practice and research, are based primarily on the platelet count and are benchmarked against the timing of discontinuation of therapeutic plasma exchange (TPE). They do not incorporate ADAMTS13 activity or the temporizing effects on the platelet count of caplacizumab, a novel anti-von Willebrand factor (VWF) nanobody. In light of these limitations, the IWG aimed to develop revised consensus outcome definitions that incorporate ADAMTS13 activity and the effects of anti-VWF therapy, by using an estimate-talk-estimate approach. The updated definitions distinguish clinical remission and clinical relapse (defined primarily by platelet count) from ADAMTS13 remission and ADAMTS13 relapse (defined by ADAMTS13 activity). The revised definitions of exacerbation and remission are benchmarked against not only the timing of discontinuation of TPE but also that of anti-VWF therapy. Retrospective validation of the revised definitions is described, although they have yet to be prospectively validated. Clinical implications of the updated outcome definitions are also discussed and an example of their application to clinical practice is provided to highlight their clinical relevance.
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Púrpura Trombocitopênica Trombótica/terapia , Proteína ADAMTS13/análise , Adulto , Consenso , Gerenciamento Clínico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Troca Plasmática , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/patologia , Recidiva , Anticorpos de Domínio Único/uso terapêutico , Resultado do Tratamento , Fator de von Willebrand/antagonistas & inibidoresRESUMO
BACKGROUND: Cold stored platelets (CSP) undergo physical changes that make them better at initiating a clot. While cold stored platelets are superior for reducing bleeding in actively bleeding patients, room temperature platelets (RTP) are better for increasing platelet count in patients requiring a prophylactic transfusion. However, whether the overhead required to maintain a dual platelet inventory of both RTP and CSP could be compensated by reduced platelet wastage resulting from the longer shelf life of CSP has not been determined. STUDY DESIGN AND METHODS: A simulation model of a regional blood supply was built, with focus on the operations of a case hospital. Two scenarios were considered: "No-CSP," in which the hospital issues only RTP, and "CSP," in which the hospital issues both RTP and CSP Within the CSP scenario, conditions were tested under which the hospital receives only RTP and converts some to cold stored platelets and a second strategy where the hospital receives CSP from the regional supplier in addition to converting RTP. RESULTS: A centralized supply of CSP is necessary since on-site conversion is limited by platelet age. Product shortages decrease with increased CSP inventory, but CSP wastage increases. It was also determined that, because relatively few RTP units can be converted on-site, RTP wastage is not significantly decreased with the introduction of CSP. CONCLUSION: Given the clinical benefits for treatment of trauma, CSP is a desirable addition to a blood formulary. However, it is unlikely that significant reductions in RTP wastage will occur because of the introduction of CSP.
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Plaquetas , Preservação de Sangue , Humanos , Preservação de Sangue/métodos , Temperatura Baixa , Contagem de Plaquetas , Hemorragia/terapiaRESUMO
BACKGROUND: Patient blood management (PBM) programs are effective at reducing transfusion-associated mortality and morbidity; however, patient engagement within the realm of PBM remains relatively unstudied. Our objectives were to develop a novel educational tool utilizing animation to educate preoperative patients about anemia and to evaluate the effectiveness of this intervention. STUDY DESIGN AND METHODS: We created a patient-facing animation for preoperative surgical patients. The animation addressed characters' health journeys from diagnosis to treatment, addressing the role of PBM. We utilized the concept of patient activation as a means to empower patients, and developed the animation to be as accessible as possible. Post-viewing, patients provided feedback utilizing an electronic survey. RESULTS: A final version of the animation can be found here: https://vimeo.com/495857315. A total of 51 participants viewed our animation, the majority of whom were planned to undergo joint replacement or cardiac surgery. Almost all (94%, N = 4) agreed that taking an active role in their health was the most important factor in determining their ability to function. The video was felt to be easy to understand (96%, N = 49), and 92% (N = 47) agreed that they had a better understanding of anemia and its treatment. After watching the animation, patients felt more certain that they could follow through with their PBM plan (98%, N = 50). DISCUSSION: To the best of our knowledge, there are no other PBM-specific patient education animations. Patients enjoyed learning about PBM though animation, and patient education may lead to better uptake of PBM interventions. We hope that other hospitals will be inspired to pursue this approach.
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Anemia , Procedimentos Cirúrgicos Cardíacos , Humanos , Anemia/diagnóstico , Anemia/terapia , Transfusão de Sangue , EscolaridadeRESUMO
BACKGROUND: Due to few teaching faculty, resource-limited settings may lack the education curricula providers need for safe practice. As safe surgery becomes an increasing priority worldwide, it is essential to improve access to critical education content including in transfusion medicine. Transfusion Camp is a longitudinal curriculum, shown to increase knowledge in postgraduate trainees. The objective was to develop a sustainable bilateral partnership between Rwanda and Canada, and to integrate Transfusion Camp into the existing curriculum of the School of Medicine and Pharmacy at University of Rwanda. METHODS: A Transfusion Camp pilot course was initiated through collaboration of experts in Rwanda and Canada. Planning occurred over 6 months via online and in-person meetings. Canadian teaching faculty adapted course content via iterative discussion with Rwandan faculty. Final content was delivered through online pre-recorded lectures by Canadian Faculty, and in-person small-group seminars by Rwandan Faculty. Project feasibility was assessed through structured evaluation and informal debriefing. RESULTS: Twenty-seven postgraduate trainees were present for the pilot course, of whom 21 (78%) submitted evaluation forms. While the structure and content of the adapted Transfusion Camp curriculum were well-received, the majority of respondents indicated a preference for in-person rather than pre-recorded lectures. Debriefing determined that future courses should focus on continuing education initiatives aimed at physicians entering or already in independent practice. CONCLUSION: A partnership between universities and blood operators in high-resource and resource-limited countries results in a transfusion medicine curriculum that is locally applicable, multidisciplinary, and supportive of learning benefitting the learners and educators alike.
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Medicina Transfusional , Humanos , Medicina Transfusional/educação , Ruanda , Região de Recursos Limitados , Canadá , CurrículoRESUMO
BACKGROUND: The optimal method of postgraduate transfusion medicine (TM) education remains understudied. One novel approach is Transfusion Camp, a longitudinal 5-day program that delivers TM education to Canadian and international trainees. The purpose of this study was to determine the self-reported impact of Transfusion Camp on trainee clinical practice. STUDY DESIGN AND METHODS: A retrospective analysis of anonymous survey evaluations from Transfusion Camp trainees over three academic years (2018-2021) was conducted. Trainees were asked, "Have you applied any of your learning from Transfusion Camp into your clinical practice?". Through an iterative process, responses were categorized into topics according to program learning objectives. The primary outcome was the rate of self-reported impact of Transfusion Camp on clinical practice. Secondary outcomes were to determine impact based on specialty and postgraduate year (PGY). RESULTS: Survey response rate was 22%-32% over three academic years. Of 757 survey responses, 68% of respondents indicated that Transfusion Camp had an impact on their practice, increasing to 83% on day 5. The most frequent areas of impact included transfusion indications (45%) and transfusion risk management (27%). Impact increased as PGY increased with 75% of PGY-4+ trainees reporting impact. In multivariable analysis, the impact of specialty and PGY varied depending on the objective. DISCUSSION: The majority of trainees report applying learnings from Transfusion Camp to their clinical practice with variations based on PGY and specialty. These findings support Transfusion Camp as an effective means of TM education and help identify high-yield areas and gaps for future curriculum planning.
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Internato e Residência , Humanos , Autorrelato , Estudos Retrospectivos , Canadá , Educação de Pós-Graduação em Medicina , Currículo , Competência ClínicaRESUMO
When combined with therapeutic plasma exchange (TPE) and immunosuppression, upfront universal administration of caplacizumab was shown to be effective in the management of immune thrombotic thrombocytopenic purpura (iTTP). However, access to this drug remains challenging in many jurisdictions. We retrospectively review results of a single-institution experience with caplacizumab over a 3-year period. During the study period, we treated 48 patients with iTTP, of which 11 (23%) received caplacizumab. Eight of these 11 patients (73%) were female; the median age was 45 years (IQR 37.0-58.5). All received TPE within 24 h of admission (median 9 exchanges, IQR 7.0-12.5), and high-dose steroids. Caplacizumab was initiated for a median of 6 days after admission (IQR 2.5-8.0) and continued for a median of 26 days (IQR 14.0-33.0). Five patients (45%) had refractory disease at caplacizumab initiation. Ten patients (91%) survived, reaching clinical remission. Platelet normalization was reached with a median of 4 days following caplacizumab initiation (IQR 1.5-4.0). Complications included minor bleeding (n = 1) and local allergic reaction (n = 1). No patients experienced TTP exacerbation; relapse occurred in two patients (18%) over 1-5 years of follow-up. Caplacizumab appeared to be effective and safe, despite delayed initiation and in the setting of refractory disease.
Immune thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening blood condition characterized by low platelets, anemia, and formation of blood clots in the small blood vessels. The condition results from a patient's immune system attacking a blood protein called ADAMTS13. The standard treatment for iTTP is plasma exchange (which replaces ADAMTS13) and medications, which suppress the immune system. Recently, a new medication, caplacizumab, has been shown to improve outcomes in iTTP, if combined with a standard treatment. However, this drug is expensive, and not readily available in all parts of the world, including Canada. In this article, we present the first Canadian experience with caplacizumab. Due to its limited access, the drug is frequently used in patients who are refractory to standard treatment or presented with severe organ damage. This contrasts with previously published studies, where it has been used upfront and in all patients with TTP. We find that caplacizumab may be safe and effective in this setting, demonstrating a low mortality rate and rapid recovery in most patients. While upfront and universal use of caplacizumab in the treatment of iTTP is optimal, our approach could be used in settings, where access to this medication is restricted.
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Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Trombose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Canadá , Troca Plasmática , Púrpura Trombocitopênica Idiopática/terapia , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Estudos Retrospectivos , Trombose/terapiaRESUMO
Importance: Red blood cell transfusion is a common medical intervention with benefits and harms. Objective: To provide recommendations for use of red blood cell transfusion in adults and children. Evidence Review: Standards for trustworthy guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed. Findings: For adults, 45 randomized controlled trials with 20â¯599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence). Conclusions and Relevance: It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.
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Transfusão de Eritrócitos , Hemoglobinas , Adulto , Criança , Humanos , Doenças Cardiovasculares , Tomada de Decisões , Transfusão de Eritrócitos/normas , Cardiopatias Congênitas , Hemoglobinas/análise , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.
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Eritroblastose Fetal , Imunoglobulinas Intravenosas , Incompatibilidade de Grupos Sanguíneos , Eritroblastose Fetal/tratamento farmacológico , Transfusão Total , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Recém-Nascido , FototerapiaRESUMO
BACKGROUND: In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets. METHODS: In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers. RESULTS: The median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P=0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the caplacizumab group and in three patients in the placebo group. Patients who received caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the caplacizumab group died from cerebral ischemia after the end of the treatment period. CONCLUSIONS: Among patients with TTP, treatment with caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo. (Funded by Ablynx; HERCULES ClinicalTrials.gov number, NCT02553317 .).
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Fibrinolíticos/uso terapêutico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Anticorpos de Domínio Único/uso terapêutico , Fator de von Willebrand/antagonistas & inibidores , Proteína ADAMTS13/metabolismo , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Fibrinolíticos/efeitos adversos , Doenças da Gengiva/induzido quimicamente , Hemorragia/induzido quimicamente , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/mortalidade , Púrpura Trombocitopênica Trombótica/terapia , Anticorpos de Domínio Único/efeitos adversos , Adulto JovemRESUMO
Our understanding of the risks associated with perioperative anemia and transfusion, in terms of increased morbidity and mortality, has evolved over the past 2 decades. By contrast, our understanding of the potential mechanisms of injury and optimal treatment strategies remains incomplete. As such, the important role of effective patient blood management (PBM) programs, which address both the effective treatment of anemia and minimizes the need for red blood cell (RBC) transfusion, is of central importance to optimizing patient care and improving patient outcomes. We report on important clinical outcomes of the Ontario Transfusion Coordinator (ONTraC Program), a network of 25 hospital sites, working in coordination over the past 20 years. Transfusion nurse coordinators were assigned to apply multimodal best practice in PBM (including recommended changes in surgical approach; diagnosis, assessment, and treatment of anemia; and adherence to more restrictive RBC transfusion thresholds). Data were collected on various clinical parameters. We further described lessons learned and difficulties encountered in this multisite PBM initiative. A significant reduction in RBC transfusions was observed for numerous indexed surgeries. For example, RBC transfusion rates for knee arthroplasty decreased from 25% in 2002 to 0.4% in 2020. For coronary artery bypass graft (CABG) surgery, transfusion rates decreased from 60% in 2002 to 27% in 2020. We also observed a decrease in RBC units utilized per transfused patient for knee (2.1 ± 0.5 [2002] vs 1.0 ± 0.6 [2020] units per patient) and CABG surgery (3.3 ± 0.6 [2002] vs 2.3 ± 1.9 [2020] units per patient). These reductions were associated with favorable clinical outcomes, including reduced length of hospital stay (P = .00003) and a reduced rate of perioperative infections (P < .001) for nontransfused versus transfused patients. These advances have been achieved with estimated savings in the tens of millions of dollars annually. Our experience and data support the hypothesis that instituting an integrated network of transfusion nurse coordinators can provide an effective provincewide PBM program, reduce RBC transfusions, improve some patient outcomes, and reduce health care costs, as an example of a "win-win-win" medical program.
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Anemia , Objetivos , Anemia/tratamento farmacológico , Anemia/terapia , Bancos de Sangue , Transfusão de Sangue , Transfusão de Eritrócitos , HumanosRESUMO
BACKGROUND: Intravenous Immune Globulin (IVIG) is used to treat numerous immune-mediated and inflammatory conditions. There is growing awareness of hemolysis, occasionally severe, as a side-effect of this therapy. While most cases are associated with anti-A and/or anti-B isoagglutinins, the frequency and mechanism of hemolysis remain poorly characterized. STUDY DESIGN AND METHODS: A prospective observational study was conducted to determine incidence, natural history and risk factors for IVIG-mediated hemolysis. A total of 99 infusions of high-dose IVIG (2 g/kg or higher) administered to 78 non-group O patients were monitored and graded according to Canadian IVIG Hemolysis Pharmacovigilance Group. Serum ferritin and C3/C4 levels were monitored as indicators of macrophage activation and complement consumption, respectively. Supplementary investigations included assessment for ABO zygosity, Secretor status, FcR polymorphisms, eluate IgG subclass, monocyte monolayer assay, and a panel of cytokines. RESULTS: Hemolysis was observed in 32 of 99 (32%) of infusions, with 19 of 99 (19%) grade 2 or higher. Hemolysis was only apparent 5-10 days after a completed IVIG infusion in 84% of cases and was associated with increases in serum ferritin without complement-consumption. In univariate analysis, increased risk was observed in group AB patients, first-time IVIG recipients, those not taking immuosuppressive medications, or patients treated with a specific IVIG brand; however, in multivariate analysis, product association was no longer observed. No other patient- or practice-related risk factors were identified. CONCLUSION: IVIG-mediated hemolysis is common and frequently severe. Monitoring for 5-10 days following an infusion should be considered in non-O patients receiving high-dose IVIG with known risk factors.
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Ferritinas/sangue , Hemólise/imunologia , Imunoglobulina G/imunologia , Imunoglobulinas Intravenosas/efeitos adversos , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Idoso , Canadá/epidemiologia , Complemento C3/imunologia , Complemento C4/imunologia , Citocinas/sangue , Feminino , Hemaglutininas/sangue , Humanos , Imunoglobulina G/classificação , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Incidência , Infusões Intravenosas , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Farmacovigilância , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion-related morbidity and mortality. A recently completed pilot trial randomized patients to pre-transfusion furosemide versus placebo but had a slower than expected enrollment rate. We sought to determine whether the lack of recruitment was due to a paucity of eligible patients or excessively restrictive eligibility criteria. MATERIALS AND METHODS: At 10 sites, eligible patients were retrospectively identified by first screening blood bank databases over one month for all transfusion episodes meeting trial inclusion criteria, defined as non-surgical patients receiving single RBC unit transfusions. The age threshold was decreased from 65 to 50 years. The first 10 patients meeting inclusion criteria then underwent detailed chart review for the exclusion criteria. The incidence of TACO and furosemide use was also recorded. RESULTS: At the 10 sites, 11 969 red cell units were transfused over 1 month and 1356 met the inclusion criteria. Of the 100 charts reviewed, 60 (60%) had no exclusion criteria. Active bleeding was the most common reason for ineligibility. There were 813 eligible transfusion episodes. Of the eligible patients, 17 (28·3%) had evidence of congestive heart failure, and furosemide was prescribed in 24 (40%). Despite the use of a lower age threshold, three cases of TACO were detected with an incidence of 3%. CONCLUSION: A large number of transfusion episodes met eligibility criteria. With a 3% incidence of TACO, 50% decrease through the use pre-transfusion furosemide and a target consent rate of 30%, a definitive trial of approximately 3000 patients could be completed within 1 year.
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Transfusão de Sangue , Furosemida/administração & dosagem , Reação Transfusional/epidemiologia , Adulto , Canadá , Bases de Dados Factuais , Diuréticos/administração & dosagem , Estudos de Viabilidade , Feminino , Hospitais , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Rh sensitization occurs when Rh(D)-negative women develop anti-Rh(D) antibodies following exposure through pregnancy or transfusion. Rh disease may cause jaundice, anemia, neurological impairment, and death. It is rare in countries where Rh Immune Globulin (RhIg) is used. Canadian Rh sensitization and disease rates are unknown. METHODS: This survey-based study was conducted using a Canadian Paediatric Surveillance Program questionnaire sent to Canadian paediatricians and paediatric subspecialists to solicit Rh disease cases from May 2016 to June 2018. Paediatricians reported Rh-positive infants ≤ 60 days of age, born to Rh-negative mothers with RhD sensitization. RESULTS: Sixty-two confirmed cases of infants affected by Rh(D) sensitization were reported across Canada. The median gestational age of neonates was term, age at presentation was 2 hours, and hemoglobin at presentation was 137.5 g/L (33 to 203 g/L). The median peak bilirubin and phototherapy duration were 280 µmol/L (92 to 771 µmol/L), and 124 hours, respectively. Thirty (48%) infants received Intravenous immune globulin (IVIG) (median two doses). Seventeen (27%) received one to three simple transfusions; 10 (16%) required exchange transfusions. Six (10%) infants presented with acute bilirubin encephalopathy, and less than five presented with seizures. Fourteen mothers with affected infants were born outside of Canada. DISCUSSION: Rh disease continues to exist in Canada. Additional efforts are needed to raise awareness of Rh disease, prevent disease, and minimize sequelae when it does occur. The ongoing global burden of Rh Disease, as well as the possibility of emerging Rh immunoglobulin refusal are among factors that could be taken into consideration in future prevention efforts.
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BACKGROUND: Hemolysis following the administration of intravenous immunoglobulin (IVIG) is an important adverse event (AE). While the monocyte monolayer assay (MMA) has been used to predict in vivo hemolysis when serologically incompatible blood may be transfused, it has also been shown to correlate with IVIG-associated hemolysis. In this study, the MMA was examined for its utility in assessing the risk of hemolysis after IVIG. STUDY DESIGN AND METHODS: Forty-two non-blood group O patients receiving high-dose IVIG (≥2 g/kg) were examined using an autologous and allogeneic MMA. Hemolysis was defined by a drop in hemoglobin of ≥1 g/L, a positive direct antiglobulin test (DAT) and eluate, and a decrease in haptoglobin or increase in lactate dehydrogenase and/or reticulocytes. RESULTS: Forty-two patients provided 50 assessable postinfusion samples, with hemolysis observed in 20 (40%) of cases. Autologous MMA using post-IVIG red blood cells significantly correlated with clinical outcomes when compared to allogeneic MMA (P = .0320 vs .5806, t test). No significant difference in receiver operating characteristics was observed when comparing autologous MMA testing against DAT for the diagnosis of IVIG-associated hemolysis. However, when using samples collected 5 to 10 days after receipt of high-dose IVIG, the autologous MMA had higher sensitivity than the DAT. CONCLUSION: MMA testing with autologous monocytes collected 5 to 10 days after receipt of high-dose IVIG can be used for the diagnosis of IVIG-associated hemolysis and may be of particular value in cases in which the Day 5 to 10 DAT is negative.
Assuntos
Testes Hematológicos , Hemólise/efeitos dos fármacos , Imunoglobulinas Intravenosas/efeitos adversos , Monócitos/metabolismo , Adulto , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , MasculinoRESUMO
Indications for therapeutic and donor apheresis continue to increase and expand into new domains of therapy. The level and amount of apheresis education in residency programs remains heterogeneous, which may translate into varying degrees of clinical confidence in providing care. The purpose of this study was to assess Canadian clinicians' perceptions of their apheresis training in order to help demonstrate a need for a concrete apheresis education in residency curricula. A 22-question survey was distributed to Canadian graduates who recently completed training (2013-2017) in the following specialties: hematology, nephrology, transfusion medicine, and hematologic pathology. Questions regarding clinician perception of their training were asked using a Likert scale. Fifty-seven survey responses (32% response rate) were obtained from recent graduates from hematology (29/57, 51%), nephrology (21/57, 37%), hematologic pathology (4/57, 7%) and transfusion medicine (3/57, 5%). Although most respondents (68%) received some form of apheresis exposure during residency, only 23% reported a formal apheresis rotation. Only 40% felt that the amount of time devoted to apheresis education was sufficient, and only four respondents (7%) felt confident providing independent apheresis care at the end of training. Overall, these findings suggest that a common, dedicated apheresis curriculum in these training programs could possibly increase knowledge and competence of trainees, and provide a more solid foundation in apheresis for future practice.
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Remoção de Componentes Sanguíneos/métodos , Internato e Residência/métodos , Avaliação das Necessidades/estatística & dados numéricos , Canadá , Humanos , Inquéritos e QuestionáriosRESUMO
We present a case of hereditary thrombotic thrombocytopenic purpura (hTTP) caused by a previously undescribed mutation in a 36-year-old woman who presented with seizures in the context of a possible infection. Her hematologic manifestations were mild, despite undetectable ADAMTS13 (A Distintegrin and Metalloproteinase with Thrombospondin Motifs 13) activity. Genetic analysis showed a homozygous variant in ADAMTS13 gene which was not previously reported but predicted to be associated with disease. She responded to plasma therapy. Her diagnosis subsequently led to the diagnosis of hTTP in her younger sibling who presented with unexplained strokes a few years earlier.
Assuntos
Púrpura Trombocitopênica Trombótica/complicações , Convulsões/etiologia , Adulto , Feminino , Humanos , Mutação , Púrpura Trombocitopênica Trombótica/genética , Convulsões/fisiopatologiaRESUMO
This narrative review critically evaluates the evidence for risk of anemia and red blood cell (RBC) transfusion. For this purpose, it assesses large prospective randomized-controlled trials (RCTs) in medical, surgical, and critical care patient populations in which the impact of specific hemoglobin transfusion thresholds are compared. In these trials, the risks of anemia relative to those of RBC transfusion are assessed. The results of published systematic reviews and meta-analyses are also discussed. Lastly, recommendations for patient blood management and treatment of anemia are explored. The main conclusion of this review emphasizes that the decision to transfuse RBCs is complex and depends on the interaction between multiple factors including the balance between the risk of anemia and the risk of RBC transfusion, existing patient comorbidities, and medical and surgical exposures. The transfusion thresholds recommended by current guidelines vary for medical and surgical patient populations. Guidelines suggesting specific transfusion thresholds for different patient populations should be viewed as a starting point for making an informed decision about RBC transfusion. Alternatives to transfusion (i.e., patient blood management), biomarkers of anemia-induced tissue hypoxia, and transfusion alternatives should continue to be evaluated in large RCTs, with the goal of improving event-free survival in critically ill and perioperative patients.
RéSUMé: Ce compte rendu narratif évalue de façon critique les données probantes concernant le risque de l'anémie et de la transfusion d'érythrocytes. Pour ce faire, nous avons évalué des études randomisées contrôlées (ERC) prospectives de grande envergure réalisées auprès de populations de patients médicaux, chirurgicaux et de soins intensifs dans lesquelles l'impact de seuils spécifiques de transfusion d'hémoglobine est comparé. Dans ces études, les risques de l'anémie sont comparés aux risques de la transfusion d'érythrocytes. Les résultats des comptes rendus systématiques et méta-analyses publiés sont également présentés. Enfin, les recommandations concernant la gestion du sang des patients et le traitement de l'anémie sont explorées. La conclusion principale de ce compte rendu souligne que la décision de transfuser des érythrocytes est complexe et dépend de l'interaction de plusieurs facteurs, notamment de l'équilibre entre le risque de l'anémie et le risque de la transfusion d'érythrocytes, les comorbidités existantes du patient, et les risques médicaux et chirurgicaux. Les seuils de transfusion recommandés par les directives actuelles sont différents pour les populations de patients médicaux et chirurgicaux. Les directives proposant des seuils de transfusion spécifiques en fonction des différentes populations de patients devraient être considérées comme point de départ pour prendre une décision informée concernant la transfusion d'érythrocytes. Les alternatives à la transfusion (c.-à-d. la gestion du sang des patients), les biomarqueurs d'une hypoxie tissulaire induite par l'anémie et les alternatives à la transfusion devraient continuer à être évalués dans des ERC d'envergure, avec pour but l'amélioration de la survie sans complication des patients en état critique et périopératoires.