Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

How do we use the National Healthcare Safety Network for Hemovigilance in Massachusetts?

BACKGROUND: Use of the National Healthcare Safety Network (NHSN) has been essential to the success of the Massachusetts Hemovigilance Program and has allowed for the timely identification of signals and trends over a defined population that correlate with national and international hemovigilance (HV) data. Here, we outline how the NHSN system is used for monitoring HV data in Massachusetts and encourage adoption of NHSN for nationwide HV surveillance. STUDY DESIGN AND METHODS: A collaboration that grew over time between local HV stakeholders and the Massachusetts Department of Public Health (MDPH) resulted in the change from a paper-based method of reporting adverse reactions and monthly transfusion activity for compliance with state requirements to replacement with statewide adoption of reporting via NHSN. RESULTS: Over 1.5 million blood products were transfused in Massachusetts between 2017 and 2021, with 3000 adverse reactions among 10 defined types reported. Using NHSN, MDPH has been able to produce numerous reports, publications, and presentations that have made previously non-obtainable HV and blood utilization data available. DISCUSSION: Although limitations to these self-reported data exist, such as lack of external validation, successful statewide implementation of NHSN for hospital blood bank reporting is possible and has benefits beyond those for regulatory oversight. It results in standardized, actionable data at both the hospital and state level, enabling inter-facility comparisons, benchmarking, and opportunities for practice improvement.

Can a Checklist Facilitate Recognition of a Transfusion-Associated Adverse Event by Prelicensure Nursing Students?

BACKGROUND: Early identification of a transfusion-associated adverse event (TAAE) is key to patient safety. Research has indicated that use of a TAAE checklist resulted in greater frequency of TAAE recognition behaviors. PURPOSE: To explore whether use of a TAAE checklist resulted in greater frequency of TAAE recognition behaviors among nursing students. METHODS: A prospective, randomized controlled study was conducted with 62 nursing students playing the role of a registered nurse in a simulation of a patient exhibiting clinical indicators of a TAAE. Subjects were randomly assigned to have or not have a TAAE checklist. Time to recognition of the TAAE was measured. RESULTS: The checklist group (CG) identified TAAEs on average 4 minutes sooner than the non-CG (P < .001). CG subjects were also significantly less likely to miss TAAEs completely. CONCLUSIONS: A checklist may improve the safety of transfusions by promoting earlier recognition and treatment of TAAEs.

Standardized reporting of pulmonary transfusion complications: Development of a model reporting form and flowchart.

BACKGROUND: Pulmonary complications of blood transfusion, including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-associated dyspnea, are generally underdiagnosed and under-reported. The international TRALI and TACO definitions have recently been updated. Currently, no standardized pulmonary transfusion reaction reporting form exists and most of the hemovigilance forms have not yet incorporated the updated definitions. We developed a harmonized reporting form, aimed at improved data collection on pulmonary transfusion reactions for hemovigilance and research purposes by developing a standardized model reporting form and flowchart. MATERIALS AND METHODS: Using a modified Delphi method among an international, multidisciplinary panel of 24 hemovigilance experts, detailed recommendations were developed for a standardized model reporting form for pulmonary complications of blood transfusion. Two Delphi rounds, including scoring systems, took place and several subsequent meetings were held to discuss issues and obtain consensus. Additionally, a flowchart was developed incorporating recently published redefinitions of pulmonary transfusion reactions. RESULTS: In total, 17 participants completed the first questionnaire (70.8% response rate) and 14 participants completed the second questionnaire (58.3% response rate). According to the results from the questionnaires, the standardized model reporting form was divided into various subcategories: general information, patient history and transfusion characteristics, reaction details, investigations, treatment and supportive care, narrative, and transfused product. CONCLUSION: In this article, we present the recommendations from a global group of experts in the hemovigilance field. The standardized model reporting form and flowchart provide an initiative that may improve data collected to address pulmonary transfusion reactions.

Incorporating the entity of under-transfusion into hemovigilance monitoring: Documenting cases due to lack of inventory.

BACKGROUND: Under-transfusion is an underreported entity within most hospitals and hemovigilance systems. While critical blood shortages are being reported more frequently, without incident codes to document instances of under-transfusion due to lack of inventory, estimating its impact on patient care as it relates to hemotherapy (HT) has hampered our ability to assess and inform strategic initiatives to combat inventory issues as well as prepare for future blood supply threats. STUDY DESIGN AND METHOD: An 11-member working group of the AABB (Association for the Advancement of Blood and Biotherapies) Hemovigilance Committee was formed in October 2020 to study the topic of under-transfusion including its potential causes and clinical expressions. The group was also charged with proposing simple definition/incident codes to be used by hemovigilance systems to document such instances. RESULTS: The working group proposed four simple incident codes under the new process code-No Blood (NB)-that can be used by hemovigilance systems to appropriately document instances of under-transfusion due to lack of inventory. The codes were described as: (1) NB 01-Inventory less than usual level due to supplier shortage; (2) NB 02-Demand for blood product exceeding usual inventory levels; (3) NB 03-Substitution with incompatible/inappropriate units; and (4) NB 04-Suboptimal dose/no transfusion given. CONCLUSION: The adoption of these codes within hemovigilance systems globally would assist in recognition and reporting instances of under-transfusion due to inventory, thus supporting development of better collection strategies, inventory management techniques as well as effective policies to improve blood safety and availability.

A Comparison of Transfusion-Related Adverse Reactions Among Apheresis Platelets, Whole Blood-Derived Platelets, and Platelets Subjected to Pathogen Reduction Technology as Reported to the National Healthcare Safety Network Hemovigilance Module.

Despite advances in transfusion safety, concerns with safety of platelet transfusions remain including platelet-related sepsis and higher reaction rates observed among patients receiving apheresis platelets (APLTs). National Healthcare Safety Network (NHSN) Hemovigilance Module (HM) data were analyzed to quantify the burden and severity of adverse reactions occurring from APLTs and whole blood-derived platelets (WBD-PLTs). Facilities participating in NHSN HM during 2010-2018 were included. Adverse reaction rates (number per 100,000 components transfused) were calculated for APLTs and WBD-PLTs stratified by severity, use of platelet additive solution (PAS), and pathogen reduction technology (PRT). Chi-square tests were used to compare rates. During the study interval, 2,000,589 platelets were transfused: 1,435,154 APLTs; 525,902 WBD-PLTs; and among APLTs, 39,533 PRT-APLTs. APLT adverse reaction rates were higher (478 vs 70/ 100,000, P< .01) and more often serious (34 vs 6/100,000; P< .01) compared with WBD-PLTs. Adverse reactions were higher among PRT-APLTs (572/100,000) and were less often serious (18/100,000) compared with non-PRT-APLTs (35/100,000) although this association was not statistically significant. Among components implicated in adverse reactions, 92% of APLTs were suspended in plasma. Compared with PRT-APLTs stored in PAS, rates were higher among units stored in plasma (760 vs 525/100,000). Most serious reactions (75%) were allergic. No transfusion-transmitted infections were reported among PRT-APLTs. APLTs were associated with a 6-fold and 2-fold higher serious adverse reaction risks compared with WBD-PLTs and PRT-APLTs, respectively. These findings demonstrate the importance of monitoring transfusion-related adverse reactions to track the safety of platelet transfusions and quantify the impact of mitigation strategies through national hemovigilance systems.

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.

Use of a Transfusion Checklist by Student Nurses to Improve Patient Safety.

Better education around the recognition of transfusion-associated adverse events is warranted. It is unknown if checklist use improves recognition by student nurses. This study examined whether using a checklist could improve transfusion-associated adverse event recognition behaviors. There was an increased frequency of transfusion-associated adverse event management behaviors in the checklist group, but overall recognition was no greater than other groups. A transfusion-associated adverse event checklist may increase patient safety by promoting identification behaviors.

Revised international surveillance case definition of transfusion-associated circulatory overload: a classification agreement validation study.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is a major cause of transfusion-related morbidity and mortality in countries with well developed transfusion services. The International Society of Blood Transfusion, the International Haemovigilance Network, and AABB (formerly American Association of Blood Banks), have developed and validated a revised definition of TACO. METHODS: International Haemovigilance Network-member haemovigilance systems (Australia, Austria, Denmark, Finland, Greece, India, Ireland, Italy, Japan, Malta, Netherlands, New Zealand, Norway, Slovenia, United Kingdom and United States) provided cases of respiratory complications categorised by their systems, including clinical parameters listed in the 2017 draft definition (part 1). Individual transfusion professionals were then invited to assess 24 case descriptions according to the draft definition (part 2). Positive and negative agreement and inter-rater agreement (κ) were calculated. Based on validation results, cases were reanalysed and slight adjustments made to yield the final 2018 TACO definition. FINDINGS: In part 1, 16 (44%) of 36 haemovigilance systems provided 178 cases, including 126 TACO cases. By use of the 2018 definition, 96 (76%) of 126 cases of TACO were in positive agreement. 19 (37%) of 52 cases were recognised as non-TACO respiratory complications. In part 2 (47 experts from 20 countries), moderate all-case agreement (κ=0·43) and TACO-specific agreement (κ=0·54) were observed. Excluding cases missing some clinical information (eg, N terminal pro-brain natriuretic peptide, distinctive chest x-ray findings, and relationship with existing respiratory co-morbidities like pneumonia and chronic obstructive pulmonary disease) improved all-case agreement to κ=0·50 (moderate) and κ=0·65 (good) for TACO cases. INTERPRETATION: The two-part validation exercise showed that the revised 2018 TACO surveillance case definition captures 76% of cases endorsed as TACO by participating haemovigilance systems. This definition can become the basis for internationally consistent surveillance reporting and contribute towards increased awareness and mitigation of TACO. Further research will require reporting more complete clinical information to haemovigilance systems and should focus on improved distinction between TACO and other transfusion respiratory complications. FUNDING: International Society of Blood Transfusion, International Haemovigilance Network, and AABB.

Evaluation of the National Healthcare Safety Network Hemovigilance Module for transfusion-related adverse reactions in the United States.

INTRODUCTION: The National Healthcare Safety Network (NHSN) Hemovigilance Module (HM) collects data on the frequency, severity, and imputability of transfusion-associated adverse events. These events contribute to significant morbidity and mortality among transfusion patients. We report results from the first systematic assessment of eight attributes of the HM. MATERIALS AND METHODS: Standard methods were used to assess the HM. Evaluation data included training materials, system modification history, and facility survey information. A concordance analysis was performed using data from the Baystate Medical Center's (Springfield, MA) electronic transfusion reporting system. RESULTS: In 2016, system representativeness remained low, with 6% (277 of 4690) of acute care facilities across 43 jurisdictions enrolled in the HM. In 2016, 48% (2147 of 4453) and 89% (3969 of 4,453) of adverse reactions were reported within 30 and 90 days of the reaction date, respectively, compared to 21% (109 of 511) and 56% (284 of 511) in 2010, demonstrating improved reporting timeliness. Data quality from most reactions was adequate, with 10% (45 of 442) misclassified transfusion-associated circulatory overload reactions, and no incomplete transfusion-transmitted infection data reported from 2010 to 2013. When compared to the Baystate system to assess concordance, 43% (24 of 56) of NHSN-reported febrile reactions were captured in both systems (unweighted kappa value, 0.47; confidence interval, 0.33-0.61). CONCLUSION: Since the 2010 HM pilot, improvements have led to enhanced simplicity, timeliness, and strengthened data quality. The HM serves an important and unique role despite incomplete adoption nationwide. Facility efforts to track and prevent transfusion-associated adverse events through systems like the NHSN HM are a key step toward improving transfusion safety in the United States.

Enhancing hemotherapy safety through pertinent diagnostic testing and electronic "provisional diagnosis" reporting: expanding roles for blood bank technologists in biovigilance and patient safety.

BACKGROUND: Suspected transfusion reaction (STR) investigations are foundational for biovigilance. Diagnostic evaluations performed by blood banks may prolong turnaround times (TATs) for final STR results reporting. We identified a quality improvement opportunity using diagnostic testing reflex algorithms and our hospital's patient electronic health record to enhance TATs regarding one aspect of STR results reporting. STUDY DESIGN AND METHODS: We conducted a descriptive quality improvement study of reported STR cases investigated by our hospital's blood bank from March 1, 2014, to December 31, 2016, using data obtained from consult reports/quality improvement databases examining the number and types of diagnostic algorithm reflex activations performed and the TATs for an electronic provisional diagnosis reporting (PDXR) related to them. RESULTS: A total of 461 STR events occurred during the study interval, of which 150 involved no reflex testing. In the remainder of cases (n = 311), a total of 448 reflex activations occurred. In those cases in which PDXR occurred (n = 446), the median PDXR TAT during the first month of implementation was 325 minutes, which progressively decreased to 70 minutes or less approximately 1 year after implementation. By the last quarter of 2015, median TATs were 60 minutes or less in length, where they remained for the duration of the study. CONCLUSION: Technologists using targeted diagnostic reflex arcs to expedite laboratory testing along with STR electronic PDXR improve communication and timely results/information dissemination, potentially aiding bedside hemotherapy-related clinical decision making.

Transfusion-Associated Circulatory Overload: Evidence-Based Strategies to Prevent, Identify, and Manage a Serious Adverse Event.

Transfusion-associated circulatory overload (TACO) is a potentially life-threatening complication of blood transfusion and is associated with increased morbidity, length of stay (hospital and intensive care unit), and hospital costs. Bedside nurses play a key role in the prevention, identification, and reporting of this complication. A common misperception is that the most frequently encountered serious adverse event during transfusion is a hemolytic reaction in a patient who receives ABO-incompatible blood. In fact, the incidence of TACO-related fatalities is higher than fatalities caused by ABO-related hemolytic reactions. Surveillance and evidence-based strategies such as clinical decision support systems have the potential to reduce the incidence of TACO and mitigate its effects. Practical suggestions for conducting bedside transfusion surveillance and future directions for improving transfusion care are presented.

Apheresis Medicine education in the United States of America: State of the discipline.

Apheresis Medicine is a medical discipline that involves a variety of procedures (based on the targeted component to be removed or collected), indications (therapeutic vs. donation), and personnel (operators, management, and medical oversight). Apheresis services are accredited and/or regulated by a number of agencies and organizations. Given the complexity and the heterogeneity of apheresis services, it has been particularly challenging to formulate educational goals and define curriculums that easily cover all aspects of Apheresis Medicine. This review summarizes the current state of the discipline in the United States of America, and some of the challenges, strategies, and resources that Apheresis Medicine educators have used to ensure that Apheresis Medicine educational programs meet the health care needs of the relevant population within regulatory and accrediting entity frameworks.

Blood Management Strategies to Reduce Transfusions After Elective Lower-Extremity Joint Arthroplasty Surgeries: One Tertiary Care Hospital's Early Experience With an Alternative Payment Model-a Total Joint "Bundle".

Blood loss associated with lower-extremity total joint arthroplasty (TJA) often results in anemia and the need for red blood cell transfusions (RBCTs). This article reports on a quality improvement initiative aimed at improving blood management strategies in patients undergoing TJA. A multifaceted intervention (preoperative anemia assessment, use of tranexamic acid, discouragement of autologous preoperative blood collection, restrictive RBCT protocols) was implemented. The results were stratified into 3 intervention periods: 1, pre; 2, peri; and 3, post. Fractional logistic regression was used to describe differences between various intervention periods. During the study period, 2511 patients underwent TJA. Compared with the preintervention period, there was 81.8% decrease in total units of RBCT during the postintervention period. Using activity-based costing (~$1000/unit), the annualized saving in RBC expenditure was $480 000. A multidisciplinary approach can be successful and sustainable in reducing RBCT and its associated costs for patients undergoing TJA.

Hemovigilance in Massachusetts and the adoption of statewide hospital blood bank reporting using the National Healthcare Safety Network.

A collaboration that grew over time between local hemovigilance stakeholders and the Massachusetts Department of Public Health (MDPH) resulted in the change from a paper-based method of reporting adverse reactions and monthly transfusion activity for regulatory compliance purposes to statewide adoption of electronic reporting via the National Healthcare Safety Network (NHSN). The NHSN is a web-based surveillance system that offers the capacity to capture transfusion-related adverse events, incidents, and monthly transfusion statistics from participating facilities. Massachusetts' hospital blood banks share the data they enter into NHSN with the MDPH to satisfy reporting requirements. Users of the NHSN Hemovigilance Module adhere to specified data entry guidelines, resulting in data that are comparable and standardized. Keys to successful statewide adoption of this reporting method include the fostering of strong partnerships with local hemovigilance champions and experts, engagement of regulatory and epidemiology divisions at the state health department, the leveraging of existing relationships with hospital NHSN administrators, and the existence of a regulatory deadline for implementation. Although limitations exist, successful implementation of statewide use of the NHSN Hemovigilance Module for hospital blood bank reporting is possible. The result is standardized, actionable data at both the hospital and state level that can facilitate interfacility comparisons, benchmarking, and opportunities for practice improvement.

Role of therapeutic apheresis in infectious and inflammatory diseases: Current knowledge and unanswered questions.

Apheresis can remove pathogens and mediators that contribute to pathogenic inflammatory responses in diseases not generally considered to be "Hematologic." Erythrocytapheresis can remove intracellular pathogens such as Babesiosis. Plasmapheresis can remove mediators of the inflammatory response in conditions such as sepsis, chronic autoimmune urticaria and malignant pertussis. Leukapheresis can remove potentially harmful leukocytes in Crohn's Disease and malignant pertussis. While apheresis can remove all of these substances, the clinical efficacy and pathophysiologic changes that occur during apheresis in these conditions are largely unknown. Hence, the clinical utility of apheresis in these conditions is largely unknown and research in these areas has the potential to benefit many patients with a variety of diseases.

Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia.

Severe aplastic anemia (AA) is a bone marrow (BM) failure (BMF) disease frequently caused by aberrant immune destruction of blood progenitors. Although a Th1-mediated pathology is well described for AA, molecular mechanisms driving disease progression remain ill defined. The NOTCH signaling pathway mediates Th1 cell differentiation in the presence of polarizing cytokines, an action requiring enzymatic processing of NOTCH receptors by γ-secretase. Using a mouse model of AA, we demonstrate that expression of both intracellular NOTCH1(IC) and T-BET, a key transcription factor regulating Th1 cell differentiation, was increased in spleen and BM-infiltrating T cells during active disease. Conditionally deleting Notch1 or administering γ-secretase inhibitors (GSIs) in vivo attenuated disease and rescued mice from lethal BMF. In peripheral T cells from patients with untreated AA, NOTCH1(IC) was significantly elevated and bound to the TBX21 promoter, showing NOTCH1 directly regulates the gene encoding T-BET. Treating patient cells with GSIs in vitro lowered NOTCH1(IC) levels, decreased NOTCH1 detectable at the TBX21 promoter, and decreased T-BET expression, indicating that NOTCH1 signaling is responsive to GSIs during active disease. Collectively, these results identify NOTCH signaling as a primary driver of Th1-mediated pathogenesis in AA and may represent a novel target for therapeutic intervention.