A review and analysis of outcomes in randomized clinical trials of plasma transfusion in patients with bleeding or for the prevention of bleeding: The BEST collaborative study.

BACKGROUND: Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence-based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes. STUDY DESIGN AND METHODS: RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023). Inclusion of publications, data extraction, and risk of bias assessments were performed in duplicate. (PROSPERO registration number is: CRD42020158581). RESULTS: In total, 5579 citations were identified in the new systematic search and 22 were included. Six additional trials were identified from the previous review, resulting in a total of 28 trials: 23 therapeutic and five prophylactic studies. An increasing number of studies in the setting of major bleeding such as in cardiovascular surgery and trauma were identified. Eighty-seven outcomes were reported with a mean of 11 (min-max. 4-32) per study. There was substantial variation in outcomes used with a preponderance of surrogate measures for clinical effect such as laboratory parameters and blood usage. CONCLUSION: There is an expanding literature on plasma transfusion to inform guidelines. However, considerable heterogeneity of reported outcomes constrains comparisons. A core outcome set should be developed for plasma transfusion studies. Standardization of outcomes will motivate better study design, facilitate comparison, and improve clinical relevance for future trials of plasma transfusion.

Gender differences in scholarly productivity of early-career transfusion medicine physicians.

BACKGROUND AND OBJECTIVES: Promotion in academic medicine requires evidence of the creation and dissemination of scholarly output, primarily through peer-reviewed publications. Studies demonstrate that scholarly activity and impact are lower for women physicians than for men physicians, especially during the early stages of their academic careers. This report reviewed physicians' academic productivity after passing their Blood Banking/Transfusion Medicine (BBTM) subspecialty exam to determine if gender discrepancies exist. METHODS: A cross-sectional analysis was designed to determine trends in scholarly activity for women physicians versus men physicians in BBTM. Indexed publications were reviewed using iCite, the National Institutes of Health (NIH) Office of Portfolio Analysis tool, from 1 January 2017 to 1 December 2021, for BBTM examinees who passed the sub-speciality fellowship exam in the years 2016 through 2018. RESULTS: Overall, women physicians had statistically significant fewer total career publications (median 6 vs. 9 cumulative papers, p = 0.03). Women published at a lower rate after passing BBTM boards, which was not statistically significant (0.7 vs. 1.3 publications per year). Other statistically significant findings include fewer early-career BBTM women physicians were first authors compared with men physicians (p = 0.03) and impact as assessed by relative citation ratio was higher for men (p = 0.01). CONCLUSIONS: This study demonstrates that there are gender differences in scholarly productivity and impact on early-career BBTM physicians. Given that this cohort of BBTM physicians are early-career professionals, the significant difference in first authorship publications between women and men physicians is especially concerning. Publication metrics should be followed to ensure equitable research environments for early-career BBTM physicians.

Plasma Adsorption with the MTx.100 Column in Critically Ill COVID-19 Patients: A Prospective Study and Propensity Score Analysis.

BACKGROUND: Early in the COVID-19 pandemic, patients with severe disease admitted to the intensive care unit (ICU) had a high incidence of mortality. We aimed to investigate whether plasma adsorption with the MTx.100 Column could improve survival. METHODS: We performed a prospective, single-arm, multicenter, Emergency Use Authorization (EUA) trial in patients admitted to the ICU with severe COVID-19 who were worsening despite standard therapy. The primary outcome was all-cause mortality on day 28. Outcomes were analyzed using both a pre-specified performance goal (PG), and a propensity score-matched (PSM) analysis from the highest enrolling center, in which patients treated with the standard of care (SOC) plus the MTx.100 Column (n = 70) were compared to a contemporaneous cohort treated at the same center with SOC only (n = 244). FINDINGS: Between May 21, 2020, and November 2, 2021, 107 patients with severe COVID-19 (mean age 58.1) at 7 US centers were enrolled and had at least one plasma adsorption treatment initiated. All-cause mortality on day 28 was 37.4% (40/107), an improvement over the prespecified PG (88.1%, p < 0.0001). There were no serious adverse events attributable to the MTx.100 Column or plasmapheresis. Improvements in most metabolic and inflammatory markers were also noted. The PSM analysis showed that survival odds were three times higher for MTx.100 Column-treated patients (95% CI: 1.56-5.88) than for those treated with SOC only. INTERPRETATION: The MTx.100 Column treatment in severe COVID-19 resulted in a lower mortality than SOC by both pre-specified PG and PSM analysis. TRIAL REGISTRATION: clinicaltrials.gov (NCT04358003).

Transfusion medicine research in Africa: Insights from investigators in the field.

BACKGROUND AND OBJECTIVES: Research in low-resource settings is inherently challenging. We sought to assess the factors that have impeded or facilitated transfusion medicine (TM) research in various African settings. MATERIALS AND METHODS: A qualitative case study was conducted of selected investigators in Africa; selection was based on productivity-spanning publication, leadership and research in TM. We designed a questionnaire to explore the factors impeding or facilitating TM research to understand the impact on the investigators' careers. Written responses were independently coded and double-checked for precision. Qualitative analysis was conducted, whereby responses were grouped thematically and clustered by relationship. The initial findings were discussed with respondents to validate and refine the interpretations. The recorded transcript was analysed and incorporated into the final analysis. RESULTS: Six investigators participated in the study. Their responses yielded 471 coded comments: 389 from the questionnaires and 82 from the ensuing discussion. The most frequently cited factors described included knowledge and intellectual abilities (n = 104), personal effectiveness (n = 99), research and governance structure (n = 97), and engagement, influence and impact (n = 75). Four relationship clusters emerged from the facilitators (n = 42), barriers (n = 28), and common approaches (n = 26) to research, informing summary themes of adaptation, collaboration, perseverance, and resiliency. CONCLUSION: Individual attributes were found to be central to a successful TM research career in African settings. However, given other public health priorities and constraints, interpersonal relationships, organizational structures and the broader research context were important to TM researchers. Overcoming complexities demands adaptation, collaboration, perseverance and resiliency.

Cold stored platelets - Increasing understanding and acceptance.

Platelet transfusions decreased the risk of morbidity and mortality secondary to thrombocytopenia. This therapy not only ameliorates platelet loss in bleeding patients,but also those with acquired dysfunction of platelets. The current standard of practice worldwide is to provide room temperature platelets (RTPs); however, there are many disadvantages to the use of RTPs such that alternative approaches have been explored. One potential approach is the integration and use of cold stored platelets (CSP), which are platelets stored at 1-6 °C, in clinical settings. CSP research studies show equivalent hemostasis and platelet dysfunction restoration compared to RTPs. In addition, publications have demonstrated advantages of CSP such as reduced bacterial contamination and wastage. Despite its benefits, the production of CSP by blood centers (BCs) and uptake and use of CSP by hospitals has remained relatively low. This review highlights the rationale for CSP production and strategies for overcoming the implementation challenges faced by BCs based on a literature review.Experiences of Consortium for Blood Availability members to integrate CSP in their BCs and clinical practices by providing variance applications are reviewed in this paper. Also, demonstrated in this manuscript are the current indications and opportunities for CSP utilization by healthcare providers.

COVID-19 and the impact on blood availability and transfusion practices in low- and middle-income countries.

BACKGROUND/CASE STUDIES: The coronavirus disease 2019 (COVID-19) pandemic disrupted the global blood supply. Low- and middle-income countries (LMICs) already experienced blood supply deficits that preceded the pandemic. We sought to characterize the challenges experienced during the pandemic, and adaptations, such as COVID-19 convalescent plasma (CCP). STUDY DESIGN/METHODS: A cross-sectional survey explored blood availability, challenges, and adaptations. The survey contained 31 questions, e-mailed in English, French, or Spanish, to selected LMIC blood transfusion practitioners. Data acquisition occurred between October 28 and December 28, 2020. A mixed methods analysis followed. RESULTS/FINDINGS: A total of 31 responses from 111 invitations represented 26 LMIC countries. Languages included English (22, 71%), Spanish (7, 22.6%), and French (2, 6.4%). Most respondents (29/31, 93.5%) collected blood; 58% also transfused blood (18/31). The supply of blood came from hospital-based blood donations (61%, 11/18); blood suppliers (17%, 3/18); and both sources (22%, 4/18). Collectively, 77.4% (24/31) of respondents experienced a decline in blood availability, ranging from 10% to 50%. Contributing factors included public fear of COVID-19 (21/24); stay-at-home measures (18/24); logistics (14/24); and canceled blood drives (16/24). Adaptations included increased collaboration within and between institutions (17/27), donor eligibility changes (21/31); social media or phone promotion (22/39); and replacement donation (3/27). Fifteen of 31 responses reported CCP donation (48.4%); CCP transfusion occurred in 6 (19.4%). The primary barrier was engaging recovered patients for donation (7/15). CONCLUSION: Our survey describes challenges experienced by LMIC blood systems during the COVID-19 pandemic. While the decline in blood supplies was severe, adaptive measures included collaboration, outreach, and CCP programs.

The impact of COVID-19 on academic productivity by female physicians and researchers in transfusion medicine.

BACKGROUND: Several studies have highlighted the disparities in gender equity that exist in different medical specialties. The COVID-19 pandemic has further heightened the inequity faced by female physicians as they are challenged by increasing household and childcare duties in addition to their professional responsibilities. Given these hurdles, fewer women than men have published in various medical disciplines. In this brief report, we wanted to determine the impact of the COVID-19 pandemic on the academic output of female physicians and researchers in transfusion medicine. STUDY DESIGN AND METHODS: We compared all articles in four transfusion medicine journals published from January 1 to July 31, 2019 with the same time period in 2020. Overall, 1024 articles were reviewed for whether they included women as first or senior authors. RESULTS: Overall, women were first authors in 45.9% (n = 458) of all publications and senior authors in 35% (n = 356) of all publications. There was a statistically significant decrease in the percentage of women as first authors between 2019 (49.1%) and 2020 (42.7%) (p = .04). There was no significant change in the percentage of women as senior authors between 2019 (35.4%) and 2020 (35.5%) (p = 0.99). CONCLUSIONS: Similar to other medical specialties, the COVID-19 pandemic has further increased the disparities faced by female researchers in transfusion medicine as evidenced by a decrease in publications with women as first authors.

Use of therapeutic plasma exchange for pediatric neurological diseases.

Therapeutic plasma exchange is used to treat neurological diseases in the pediatric population. Since its first use in pediatric patients with hepatic coma in the form of manual whole blood exchange, therapeutic plasma exchange has been increasingly used to treat these disorders of the nervous system. This expansion is a result of improved techniques and apheresis instruments suitable for small children, as well as the recognition of its applicability to many diseases in the pediatric population. This review provides a historical overview of the use of therapeutic apheresis in children and highlights the most common applications for therapeutic plasma exchange to treat neurological disorders in children.

Ultrasound-based criteria for adequate peripheral venous access in therapeutic apheresis procedures.

BACKGROUND: Apheresis procedures require adequate vascular access to achieve adequate inlet flow rates. Central dialysis-type catheters are often used in apheresis, despite their multiple risks. Peripheral venous access is a safe and effective option for many patients. AIM: We previously demonstrated that ultrasound guidance reduces central venous catheter use in apheresis patients; however, no validated criteria for preprocedural evaluation of peripheral veins exist. Here, we hypothesized that ultrasound-based criteria could predict the adequacy of a peripheral vein for apheresis procedures. PATIENTS/METHODS: In this pilot cohort study, we reviewed the procedural outcomes for 50 cases of peripheral venous procedures that used our ultrasound-based criteria. RESULTS: Of the procedures that met our criteria, 96% (46/48) were successfully completed. Overall, our criteria had 100% sensitivity, 50% specificity, 96% positive predictive value, and 100% negative predictive value. CONCLUSION: Our criteria justify an evidence-based ultrasound-guided standard for evaluation of peripheral venous access for apheresis procedures.

Provision of COVID-19 Convalescent Plasma in a Resource-Constrained State.

BACKGROUND: Arkansas is a rural state of 3 million people. It is ranked fifth for poverty nationally. The first case of coronavirus disease 2019 (COVID-19) in Arkansas occurred on 11 March 2020. Since then, approximately 8% of all Arkansans have tested positive. Given the resource limitations of Arkansas, COVID-19 convalescent plasma (CCP) was explored as a potentially lifesaving, therapeutic option. Therefore, the Arkansas Initiative for Convalescent Plasma was developed to ensure that every Arkansan has access to this therapy. STUDY DESIGN AND METHOD: This brief report describes the statewide collaborative response from hospitals, blood collectors, and the Arkansas Department of Health (ADH) to ensure that CCP was available in a resource-limited state. RESULTS: Early contact tracing by ADH identified individuals who had come into contact with "patient zero" in early March. Within the first week, 32 patients tested positive for COVID-19. The first set of CCP collections occurred on 9 April 2020. Donors had to be triaged carefully in the initial period, as many had recently resolved their symptoms. From our first collections, with appropriate resource and inventory management, we collected sufficient CCP to provide the requested number of units for every patient treated with CCP in Arkansas. CONCLUSIONS: The Arkansas Initiative, a statewide effort to ensure CCP for every patient in a resource-limited state, required careful coordination among key players. Collaboration and resource management was crucial to meet the demand of CCP products and potentially save lives.

Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin-induced thrombocytopenia: A systematic review.

BACKGROUND: Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. STUDY DESIGN AND METHODS: We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. RESULTS: After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were equally used as initial therapy. Heparin re-exposure occurred without thrombotic event in 29 TPE-treated patients and three IVIG-treated patients. CONCLUSION: In patients with HIT, both TPE and IVIG are used for initial therapy or treatment of refractory HIT. However, TPE is more commonly used in patients undergoing CPB. Prospective studies may help clarify which treatment is indicated in HIT population subsets.

Apheresis medicine in the era of advanced telehealth technologies: An American Society for Apheresis position paper Part I: Understanding the basic technologies and apheresis medicine practice models.

The wide spread availability and use of sophisticated high-speed telecommunication networks coupled with inexpensive and easily accessible computing capacity have catalyzed the creation of new tools and strategies for healthcare delivery. Such tools and strategies are of value to apheresis medicine (AM) practitioners if they improve delivery of patient care, enhance safety during a therapeutic apheresis (TA) intervention, facilitate care access, advance technical capabilities of apheresis devices, and/or elevate quality performance within TA programs. In the past several years, healthcare delivery systems' adoption of telecommunication technologies has been fostered by organizational financial and quality improvement objectives. More recently, adoption of telehealth technologies has been catalyzed by the COVID-19 pandemic as these technologies enhance both patient and provider safety in an era of social distancing. These changes will also influence the delivery of TA services which now can be generally viewed in a tripartite model format comprised of traditional hospital-based fixed site locales, mobile TA operations and lately an evolving telemedicine remote management model now reffered to as telapheresis (TLA). This communication developed by the Public Affairs and Advocacy Committee of the American Society for Apheresis (ASFA) and endorsed by its Board of Directors, reviews and describes various aspects of established and evolving electronic technologies related to TLA and the practice of AM. In subsequent companion publications, additional aspects to TLA will be explored and ASFA's vision of reasonable, regulatory compliant and high-quality TLA practices will be expounded.

Therapeutic plasma exchange for neuromyelitis optica spectrum disorder: A multicenter retrospective study by the ASFA neurologic diseases subcommittee.

IMPORTANCE: Neuromyelitis optica/neuromyelitis optica spectrum disorder patients' response to therapeutic plasma exchange (TPE) is currently incompletely characterized. OBJECTIVE: Our study aims to understand the clinical status improvement of neuromyelitis optica/neuromyelitis optica spectrum disorder patients treated with TPE. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter retrospective study conducted between 1 January 2003 and 31 July 2017 at 13 US hospitals performing apheresis procedures. Subjects studied were diagnosed with neuromyelitis optica/neuromyelitis optica spectrum disorder who received TPE during presentation with acute disease. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical status improvement in patients treated with TPE. Secondary measures were procedural and patient characteristics associated with response to treatment. RESULTS: We evaluated 114 patients from 13 institutions. There was a female predilection. The largest ethnic group affected was non-Hispanic Caucasian. The average age of diagnosis was 43.1 years. The average time to diagnosis was 3.1 years. On average, five procedures were performed during each treatment series. The most commonly performed plasma volume exchange was 1.0 to 1.25 using 5% albumin as replacement fluid. Most patients (52%) did not require an additional course of TPE and noted "mild" to "moderate" clinical status improvement. Maximal symptom improvement appeared by the fourth or fifth TPE treatment. CONCLUSION AND RELEVANCE: TPE improved the clinical status of patients. Adults responded more favorably than children. Procedural characteristics, including number of TPEs, plasma volume exchanged, and replacement fluid used, were similar between institutions. TPE was well-tolerated and had a low severe adverse event profile.

Electronic patient identification for sample labeling reduces wrong blood in tube errors.

BACKGROUND: Wrong blood in tube (WBIT) errors are a preventable cause of ABO-mismatched RBC transfusions. Electronic patient identification systems (e.g., scanning a patient's wristband barcode before pretransfusion sample collection) are thought to reduce WBIT errors, but the effectiveness of these systems is unclear. STUDY DESIGN AND METHODS: Part 1: Using retrospective data, we compared pretransfusion sample WBIT rates at hospitals using manual patient identification (n = 16 sites; >1.6 million samples) with WBIT rates at hospitals using electronic patient identification for some or all sample collections (n = 4 sites; >0.5 million samples). Also, we compared WBIT rates after implementation of electronic patient identification with preimplementation WBIT rates. Causes and frequencies of WBIT errors were evaluated at each site. Part 2: Transfusion service laboratories (n = 18) prospectively typed mislabeled (rejected) samples (n = 2844) to determine WBIT rates among samples with minor labeling errors. RESULTS: Part 1: The overall unadjusted WBIT rate at sites using manual patient identification was 1:10,110 versus 1:35,806 for sites using electronic identification (p < 0.0001). Correcting for repeat samples and silent WBIT errors yielded overall adjusted WBIT rates of 1:3046 for sites using manual identification and 1:14,606 for sites using electronic identification (p < 0.0001), with wide variation among individual sites. Part 2: The unadjusted WBIT rate among mislabeled (rejected) samples was 1:71 (adjusted WBIT rate, 1:28). CONCLUSION: In this study, using electronic patient identification at the time of pretransfusion sample collection was associated with approximately fivefold fewer WBIT errors compared with using manual patient identification. WBIT rates were high among mislabeled (rejected) samples, confirming that rejecting samples with even minor labeling errors helps mitigate the risk of ABO-incompatible transfusions.

Therapeutic plasma exchange for management of heparin-induced thrombocytopenia: Results of an international practice survey.

INTRODUCTION: Anti-heparin/platelet factor 4 antibody immune complexes resulting from heparin-induced thrombocytopenia (HIT) are removed by therapeutic plasma exchange (TPE). We sought to define TPE in HIT practice patterns using an international survey. METHODS: A 31-item online survey was disseminated through the American Society for Apheresis. After institutional duplicate responses were eliminated, a descriptive analysis was performed. RESULTS: The survey was completed by 94 respondents from 78 institutions in 18 countries. Twenty-nine institutions (37%) used TPE for HIT (YES cohort) and 49 (63%) did not (NO cohort). Most NO respondents (65%) cited "no requests received" as the most common reason for not using TPE. Of the 29 YES respondents, 10 (34%) gave incomplete information and were excluded from the final analysis, leaving 19 responses. Of these, 18 (95%) treated ≤10 HIT patients over a 2-year period. The most common indications were cardiovascular surgery (CS; 63%) and HIT-associated thrombosis (HT; 26%). The typical plasma volume processed was 1.0 (63% CS and 58% HT). For CS, the typical replacement fluid was plasma (42%) and for HT, it was determined on an individual basis (32%). For CS, patients were treated with a set number of TPE procedures (37%) or laboratory/clinical response (37%). For HT, the number of TPE procedures typically depended on laboratory/clinical response (42%). CONCLUSION: In a minority of responding institutions, TPE is most commonly used in HIT to prophylactically treat patients who will undergo heparin re-exposure during CS. Prospective studies are needed to more clearly define the role of TPE in HIT.

Donath-Landsteiner test.

CONCLUSIONS: The Donath-Landsteiner (DL) test is a serologic test used to detect the presence of a biphasic hemolysin. This autoantibody is seen in patients with paroxysmal cold hemoglobinuria. The test relies on the characteristic cold binding of an IgG autoantibody with specificity to the P blood group antigen. This autoantibody causes complement-mediated red blood cell (RBC) lysis when warmed to body temperature. In this review, we describe the various methods for performing the DL test-namely a direct test, an indirect test, an indirect test with modifications such as the use of enzyme-treated RBCs and two stages, and an indirect antiglobulin DL test-and highlight the advantages and disadvantages of each. Our focus is on the indirect testing method as it is most commonly used in blood bank laboratories.

Vascular access for therapeutic plasma exchange.

Therapeutic plasma exchange is an apheresis modality in which plasma is separated from the blood cellular components ex vivo, discarded, and replaced with an isosmotic fluid (most commonly 5% albumin) to maintain appropriate oncotic pressure in the patient. Therapeutic plasma exchange is used in the treatment of many diseases and indications. The recent seventh edition of the American Society for Apheresis guidelines indicates approximately 72 diseases and 116 indications for which therapeutic plasma exchange may be effective. One of the critical aspects for the successful performance of therapeutic plasma exchange is appropriate vascular access to provide high blood flow for the collection and return phases of the procedure, especially because most patients who need therapeutic plasma exchange will require more than one treatment over days to weeks. This article provides an overview of the characteristics of therapeutic plasma exchange, the clinical diseases and indications that may be treated with therapeutic plasma exchange, and the different types of vascular access employed, with their advantages and disadvantages. The latter may include peripheral venous access and intravascular or implantable access devices, such as arteriovenous grafts and fistulas, central venous catheters, and central venous catheters tunneled with ports.

The utility of therapeutic plasma exchange for amphotericin B overdose.

Medication error is a preventable cause of morbidity and death in the inpatient population. We describe a patient with an antifungal overdose treated with therapeutic plasma exchange (TPE). The patient was diagnosed with cryptococcal meningitis and received an acute overdose of amphotericin B deoxycholate instead of the prescribed liposomal amphotericin B. Consequently, the patient developed clinical symptoms including tremors, hypertension, visual hallucinations, vertigo, fever, and acute renal failure. A series of four TPEs was emergently initiated, resulting in complete resolution of most symptoms.