Survey of newborn direct antiglobulin testing practice in United States and Canadian transfusion services.

BACKGROUND: We hypothesized that variability in practice exists for newborn immunohematology testing due to lack of consensus guidelines. We report the results of a survey assessing that variability at hospitals in the United States and Canada. STUDY DESIGN AND METHODS: An AABB Pediatric Subsection working party developed and validated a survey of newborn immunohematology testing practice. The survey was sent electronically to transfusion service leadership at teaching institutions. RESULTS: The response rate was 67% (61/91); 56 surveys meeting inclusion criteria were analyzed. Approximately 90% (50/56) were from birth hospitals and 16.1% (9/56) were from pediatric hospitals. Newborn immunohematology testing is ordered as a panel by 66.0% (33/50) of birth hospitals. ABO group and DAT is mandated before discharge in 14/56 (25.0%) and 13/56 (23.2%), respectively. About 76.8% (43/56) selectively perform a DAT according to blood blank or clinical parameters. The most common DAT practices include anti-IgG only testing by 73.2% (41/56) and use of umbilical cord specimen type by 67.9% (38/56). A positive DAT is a critical value for 26.8% (15/56) and followed with eluate testing when a maternal antibody screen is positive for 48.2% (27/56). In the setting of a non-ABO maternal red cell antibody, 55.4% (31/56), phenotype neonatal red cells when the DAT is positive. Group O RBC are transfused irrespective of the DAT result for 82.1%, (46/56). CONCLUSION: There is variability in newborn immunohematology testing and transfusion practice and potential overutilization of the DAT. Evidence-based consensus guidelines should be developed to standardize practice and to improve safety.

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.

Health literacy and knowledge of chronic transfusion therapy in adolescents with sickle cell disease and caregivers.

BACKGROUND: Patients with sickle cell disease (SCD) may require chronic transfusion therapy (CTT) for prevention of stroke or other complications. Limited health literacy (HL) is common and is associated with poor health-related knowledge and outcomes in chronic disease. We sought to assess HL and transfusion knowledge in patients with SCD on CTT and their caregivers. METHODS: A cross-sectional study of patients was conducted in outpatient hematology clinics. Forty-five pairs of adolescent patients and caregivers and 20 caregivers of pre-adolescent patients completed the Newest Vital Sign HL assessment and answered questions assessing SCD and transfusion knowledge. Community-level median income and unemployment rates were estimated from Census data. We computed the correlation of HL with knowledge and compared each to Census variables, payor status, educational attainment, and stroke. RESULTS: HL was inadequate in 22 (34%) caregivers and 31 (69%) adolescents. Adequate caregiver HL was associated with higher educational attainment but not community-level socioeconomics or payor status. Mean knowledge score was lower in adolescents than in caregivers and correlated with age in adolescents (r = 0.42, P = .004). HL correlated with knowledge (r = 0.46, P < .0001). There were no significant correlations of HL or knowledge between adolescents and their caregivers. Neither HL nor knowledge was associated with prior stroke. The greatest knowledge was demonstrated for iron overload and SCD genotype, whereas knowledge gaps existed in alloimmunization, indication for CTT, and SCD curative therapy. CONCLUSIONS: Enhanced educational resources in transfusion therapy, alloimmunization, and curative therapy are needed for patients with SCD and caregivers of all HL levels.

Epidemiology of therapeutic apheresis with a multidisciplinary approach at a high volume pediatric center.

INTRODUCTION: Therapeutic apheresis (TA) is used inconsistently in pediatric populations. We seek to define our multidisciplinary institutional practice. METHODS: We conducted a retrospective chart review of patients receiving TA from January 1, 2012 through October 31, 2015. Data collected included demographics, American Society of Apheresis (ASFA) indication, complications, and mortality. RESULTS: Over 46 months, 1198 TA procedures were conducted on 289 patients ranging in age from 5 months to 21 years with weights ranging from 4.76 to 170.3 kg (16 procedures in patients <10 kg). The procedures were 86% therapeutic plasma exchange, 10% red blood cell exchange, 4% extracorporeal photopheresis, and 5 leukocytapheresis procedures. TA was initiated in different clinical environments: 41% outpatient, 37% intensive care, 15% general inpatient, and 7% operating room. The ASFA category (6th edition) indications for the 1198 procedures included: 44% category I, 25% category II, 23% category III, a single category IV procedure, and the remainder (8%) uncategorized by ASFA. The rate of procedure failure and procedure-related mortality are 1 and 0%, respectively. Case mortality rate was 4%. CONCLUSION: At a large volume pediatric hospital, TA is commonly used and can be performed safely in a variety of settings by a multidisciplinary team. This demographic review catalogs the number and type of procedures performed as a second-line therapy or on the basis of limited evidence. Additional collaborative investigation is needed to evaluate unique implications of TA in pediatrics to maximize efficacy while preserving safety.

Impact of red blood cell alloimmunization on sickle cell disease mortality: a case series.

BACKGROUND: Although red blood cell (RBC) transfusion represents an integral component of sickle cell disease (SCD) care, transfusion support for some patients can result in alloimmunization to RBC antigens. Alloimmunized patients with SCD appear to experience worse survival compared to nonalloimmunized patients. While this difference in mortality may in part be due to underlying immunologic differences related to disease severity, it may also reflect direct clinical consequences of RBC alloimmunization. Alloimmunized patients have an increased risk of serious hemolytic transfusion reactions (HTRs) and may not receive adequate RBC transfusion support due to lack of compatible RBC units. CASE REPORT: This study reports on five RBC alloimmunized patients with SCD who died, to illustrate the concept that RBC alloimmunization itself contributes to premature death. RESULTS: The clinical course for each of the reported patients provides insight into the direct and indirect consequences of RBC alloimmunization, where patients experienced delayed HTRs or did not receive needed RBC transfusions. CONCLUSION: Future work examining the clinical impact of RBC alloimmunization should not only consider HTRs but should also address the potential consequences associated with difficulties in obtaining compatible blood.

The top clinical trial opportunities in therapeutic apheresis and neurology.

OBJECTIVE: The National Heart, Lung, and Blood Institute, of The National Institutes of Health, convened the 2012 State-of-the-Science Symposium in therapeutic apheresis (TA) with the goals of identifying and prioritizing future research concept proposals to optimize the use of TA over the next decade. METHODS: Six subcommittees, including neurology, were formed based on organ system, pathophysiology, and technology/special considerations. The subcommittees consisted of physicians, clinical subject matter experts, and basic scientists. Each subcommittee developed concept proposals that were presented, evaluated, and prioritized based on scientific importance, clinical significance, and feasibility. RESULTS: The neurology subcommittee developed eight concept proposals. The proposals include therapeutic plasma exchange (TPE) in neuromyelitis optica; TPE versus intravenous immunoglobulin (IVIG) in anti-muscle specific kinase associated myasthenia gravis, severe acute disseminated encephalomyelitis, and anti-NMDA encephalitis; extracorporeal photopheresis in relapsing remitting multiple sclerosis and polymyositis; fibrinogen/low-density lipoprotein apheresis in idiopathic sudden sensorineural hearing loss; and creation of a rare neurologic disease registry and biorepository. CONCLUSIONS: Key clinical research priorities to evaluate and optimize the use of TA on selected neurologic disorders exist. The research opportunities if addressed would provide evidence-based data to inform the care of patients with these selected neurologic diseases.

Rejuvenation capacity of red blood cells in additive solutions over long-term storage.

BACKGROUND: Red blood cells (RBCs) are Food and Drug Administration (FDA)-approved for 42-day storage with the use of additive solutions (ASs). However, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) levels in the RBCs decline over this time. These constituents may be restored by treatment with rejuvenation (REJ) solutions. This study was done to assess the response capability of RBCs from 30 to 120 days of storage in three FDA-licensed RBC storage solutions after incubation with a rejuvenating solution of pyruvate, inosine, phosphate, and adenine. STUDY DESIGN AND METHODS: Three units each of RBCs in approved AS (AS-1 [Adsol, Fenwal, Inc.], AS-3 [Nutricel, Medsep Corp.], and AS-5 [Optisol, Terumo Corp.]) were stored under standard conditions at 1 to 6°C for up to 120 days. Aliquots (4 mL) on Days 30, 42, 60, 80, 100, and 120 (± 2 days) were REJ by incubating with Rejuvesol (Encyte Corp.). Control untreated and REJ aliquots were extracted using perchloric acid and stored at -80°C until assayed for 2,3-DPG and ATP. RESULTS: RBCs responded to REJ by increasing DPG and ATP contents. The response declined linearly at 0.070 ± 0.008 µmol DPG/g hemoglobin (Hb)/day and 0.035 ± 0.004 µmol ATP/g Hb/day with no differences between ASs. CONCLUSION: We conclude that Rejuvesol is able to restore ATP and 2,3-DPG levels in RBCs stored up to 120 days in AS. The response diminishes as storage time increases. This rejuvenation (REJ) capability does not seem useful for routine assessment of RBC anabolic capacity in research programs, but may be useful to the investigator when studying unique and novel treatment methods.

Development, Implementation, and Evaluation of a Fourth-Year Medical School Elective Course in Blood Banking and Transfusion Medicine.

Objectives: Knowledge of transfusion medicine by medical students is limited. Transfusion medicine physicians developed, implemented, and evaluated a half-day elective on transfusion medicine for fourth-year medical students. Methods: The course included a didactic lecture with integrated audience response questions and role-playing, as well as a "Jeopardy"-style game to review the material. The same 10-question knowledge quiz was administered before and after the elective. Results: Both knowledge quizzes were taken by 102 students. An average score of 3.3 was obtained on the initial quiz, with only three (3%) students having a passing score (≥6 correct questions). The average score after the elective was 6.6, with 83 (81%) students having a passing score. Students found the elective was informative (62 students, 60.8%), very useful (56, 54.9%), and practical (51, 50%), although some thought it was challenging (22, 21.6%). Conclusions: A short course for medical students that allowed repetition of concepts using several teaching modalities improved their knowledge in transfusion medicine.

Impact of Red Blood Cell Antigen Matching on Alloimmunization and Transfusion Complications in Patients with Sickle Cell Disease: A Systematic Review.

Red blood cells (RBC) transfusion is critical in managing acute and chronic complications in sickle cell disease (SCD); however, it is complicated by RBC alloimmunization, iron overload, transfusion reactions and infection. Several reports documented an increased incidence of alloantibodies in transfused individuals with SCD, especially for Rh and Kell antigens. As a result, the National Institutes of Health Expert Panel and British Society for Haematology guidelines recommend primary matching for C/c, E/e and K antigens in addition to ABO/RhD for RBC transfusions. However, the evidence supporting these recommendations was cited as limited and understanding of alloimmunization in SCD is evolving. To examine the limitations of the evidence, we undertook a systematic review of evidence behind recommendations for limited and extended serologic and genotypic RBC antigen matching to reduce alloimmunization, autoimmunization and transfusion reactions. Searches of PubMed, Embase, Cochrane, and Web of Science databases using MeSH index and free text terms between 1976 through October 2015 and papers and captured through July 2016 through review references in papers, word of mouth, and ongoing Google Scholar and Medline Alerts identified 303 unique articles. Nineteen articles met inclusion criteria and were classified by the Oxford Centre Evidence Based levels of evidence. Strengthening the Reporting of Observational Studies in Epidemiology checklists were completed for 18 of the 19 studies. There were no prospective randomized controlled trials. Sixteen of the articles were cohort studies, two were cross-sectional studies, and one decision tree model examining costs. Low-quality evidence from observational cohort studies supports that alloimmunization prevalence can be decreased by extending serological RBC antigen matching. Transfusion reactions are generally poorly and inconsistently reported. There was no evidence reporting the effect prophylactic genotypic matching has on alloimmunization, autoimmunization or transfusion reactions. There were no studies comparing prophylactic genotypic matching to serologic matching. High-quality evidence was lacking to support clinical decision making regarding best transfusion practices. Multicenter prospective randomized clinical trials are needed to determine best strategies for reducing the rate of alloimmunization using serologic and genotypic matching.

Pediatric Tandem Therapeutic Apheresis: A Multidisciplinary Approach.

The epidemiology, safety, and efficacy of pediatric multiple tandem extracorporeal therapies are not well understood. We conducted a retrospective chart review of therapeutic apheresis (TA) from January 1, 2012 to October 31, 2015. We collected procedural/clinical demographics, American Society for Apheresis (ASFA) indication, complications, and mortality. One hundred eighty tandem TA procedures were performed in 53 patients. Median age was 9 years (range: 2 months to 21 years) with a median weight of 28 kg (range: 6-170.3 kg) with nine patients weighing < 10 kg. Forty-five percent of patients were in tandem with continuous veno-venous hemofiltration (CVVH), 21% cardiopulmonary bypass (CPB), 4% extracorporeal membrane oxygenation (ECMO), and 11% had multiple extracorporeal therapies (CVVH and ECMO). Common indications were solid organ transplant (50% cardiac, 13% renal) and sepsis-induced thrombocytopenia-associated multiple organ failure (26%). Equipment (4%) and patient (4%) complications occurred, with rare failure (1%) and no procedure-related mortality. Tandem procedures are used in critically ill pediatric patients with higher morbidity and mortality (21%) than typical TA patients. The high percentage of patients outside of category I or II (83%) underscores the emerging nature of tandem extracorporeal therapies and need for further investigation.

Synchronous Central Nervous System Atypical Teratoid/Rhabdoid Tumor and Malignant Rhabdoid Tumor of the Kidney: Case Report of a Long-Term Survivor and Review of the Literature.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) with synchronous or metachronous extra-CNS disease is a rare childhood malignancy with a dismal prognosis. CASE DESCRIPTION: We report a 7-week-old female with metastatic AT/RT and synchronous malignant rhabdoid tumor of the kidney who received an intensive multimodal approach combining surgical resection, intrathecal chemotherapy, and high-dose chemotherapy with autologous peripheral blood stem cell transplant (PBSCT). She is currently 24 months old without any evidence of disease. In addition, we completed an extensive literature review of cases with CNS AT/RT and synchronous or metachronous extra-CNS primary tumors. To date, 31 pediatric cases have been reported, and the median overall-survival was 6 months after diagnosis. The only 3 survivors received autologous PBSCT, and 2 of these patients had complete resection of their CNS tumor. CONCLUSIONS: The rarity of CNS AT/RT with extra-CNS primary disease and the lack of standard treatment contribute to its reported dismal prognosis. We report a case of a long-term survivor with metastatic AT/RT and synchronous extra-CNS primary tumor. Maximal surgical resection, intrathecal chemotherapy, and consolidative autologous PBSCT may improve prognosis and avoid radiation.

Genotyping Applications for Transplantation and Transfusion Management: The Emory Experience.

Current genotyping methodologies for transplantation and transfusion management employ multiplex systems that allow for simultaneous detection of multiple HLA antigens, human platelet antigens, and red blood cell (RBC) antigens. The development of high-resolution, molecular HLA typing has led to improved outcomes in unrelated hematopoietic stem cell transplants by better identifying compatible alleles of the HLA-A, B, C, DRB1, and DQB1 antigens. In solid organ transplantation, the combination of high-resolution HLA typing with solid-phase antibody identification has proven of value for highly sensitized patients and has significantly reduced incompatible crossmatches at the time of organ allocation. This database-driven, combined HLA antigen/antibody testing has enabled routine implementation of "virtual crossmatching" and may even obviate the need for physical crossmatching. In addition, DNA-based testing for RBC antigens provides an alternative typing method that mitigates many of the limitations of hemagglutination-based phenotyping. Although RBC genotyping has utility in various transfusion settings, it has arguably been most useful for minimizing alloimmunization in the management of transfusion-dependent patients with sickle cell disease or thalassemia. The availability of high-throughput RBC genotyping for both individuals and large populations of donors, along with coordinated informatics systems to compare patients' antigen profiles with available antigen-negative and/or rare blood-typed donors, holds promise for improving the efficiency, reliability, and extent of RBC matching for this population.

Research Opportunities to Improve Neonatal Red Blood Cell Transfusion.

Red blood cell (RBC) transfusion is a common and lifesaving therapy for anemic neonates and infants, particularly among those born prematurely or undergoing surgery. However, evidence-based indications for when to administer RBCs and adverse effects of RBC transfusion on important outcomes including necrotizing enterocolitis, survival, and long-term neurodevelopmental impairment remain uncertain. In addition, blood-banking practices for preterm and term neonates and infants have been largely developed using studies from older children and adults. Use of and refinements in emerging technologies and advances in biomarker discovery and neonatal-specific RBC transfusion databases may allow clinicians to better define and tailor RBC transfusion needs and practices to individual neonates. Decreasing the need for RBC transfusion and developing neonatal-specific approaches in the preparation of donor RBCs have potential for reducing resource utilization and cost, improving outcomes, and assuring blood safety. Finally, large donor-recipient-linked cohort studies can provide data to better understand the balance of the risks and benefits of RBC transfusion in neonates. These studies may also guide the translation of new research into best practices that can rapidly be integrated into routine care. This review highlights key opportunities in transfusion medicine and neonatology for improving the preparation and transfusion of RBCs into neonates and infants. We focus on timely, currently addressable knowledge gaps that can increase the safety and efficacy of preterm and term neonatal and infant RBC transfusion practices.

Pediatric Therapeutic Apheresis: A Critical Appraisal of Evidence.

Apheresis technology has progressed significantly over the last 50-60 years from a predominately blood donation-based procedure to one that now includes a variety of therapeutic modalities. The last 25 years also has seen an increase in the number of diseases treated by therapeutic apheresis (TA) modalities. Because of ethical considerations, therapeutic modalities are often vetted first in adult populations before establishing utility in pediatric patients. TA is no different. The majority of published studies involve adult patients. Pediatric apheresis studies are traditionally retrospective, single-center experiences, single case reports, or case series. To confirm this, we evaluated the peer-reviewed published literature to assess the level of evidence of clinical pediatric apheresis studies published in the last 21 years. Adverse events experienced by pediatric patients undergoing TA procedures and procedural modifications necessary to accommodate pediatric patients receiving TA were also explored. Consideration was given to differences in disease outcomes in pediatric vs adult patients and evolution of TA treatment indications. A systematic search of the literature yielded >1000 pediatric apheresis publications. Only 370 articles specifically assessed TA in the treatment of a pediatric disease. Of those, the majority (98%) were single-center experiences, single case reports, or case series. The remaining 2% were prospective cohort studies or randomized controlled trials. This first formal assessment of the pediatric apheresis literature confirms the findings of previous anecdotal reports and expert opinion.