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Each year the AABB Clinical Transfusion Medicine Committee (CTMC) procures a synopsis highlighting new, important, and clinically relevant studies in the field of transfusion medicine (TM). This has been made available as a publication in Transfusion since 2018.CTMC members reviewed and identified original manuscripts covering TM-related topics published electronically (ahead-of-print) or in print from December 2020 to December 2021. Selection of publications was discussed at committee meetings and chosen based on perceived relevance and originality. Next, committee members worked in pairs to create a synopsis of each topic, which was then reviewed by additional committee members. The first and senior authors assembled the final manuscript. Although this synopsis is extensive, it is not exhaustive, and some articles may have been excluded or missed.The following topics are included: blood products; convalescent plasma; donor collections and testing; hemoglobinopathies; immunohematology and genomics; hemostasis; patient blood management; pediatrics; therapeutic apheresis; and cell therapy.This synopsis highlights and summarizes recent key developments in TM and may be useful for educational purposes.

Background: Platelet transfusion is a potentially life-saving therapy for actively bleeding patients, ranging from those undergoing planned surgical procedures to those suffering unexpected traumatic injuries. Platelets are currently stored at room temperature (20°C–24°C) with a maximum storage duration of 7 days after donation. The CHIlled Platelet Study trial will compare the efficacy and safety of standard room temperature–stored platelets with platelets that are cold-stored (1°C–6°C), that is, chilled, with a maximum of storage up to 21 days in adult and pediatric patients undergoing complex cardiac surgical procedures. Methods/Results: CHIlled Platelet Study will use a Bayesian adaptive design to identify the range of cold storage durations for platelets that are non-inferior to standard room temperature–stored platelets. If cold-stored platelets are non-inferior at durations greater than 7 days, a gated superiority analysis will identify durations for which cold-stored platelets may be superior to standard platelets. We present example simulations of the CHIlled Platelet Study design and discuss unique challenges in trial implementation. The CHIlled Platelet Study trial has been funded and will be implemented in approximately 20 clinical centers. Early randomization to enable procurement of cold-stored platelets with different storage durations will be required, as well as a platelet tracking system to eliminate platelet wastage and maximize trial efficiency and economy. Discussion: The CHIlled Platelet Study trial will determine whether cold-stored platelets are non-inferior to platelets stored at room temperature, and if so, will determine the maximum duration (up to 21 days) of storage that maintains non-inferiority. Trial registration: ClinicalTrials.gov, NCT04834414

Since 1986, the American Society for Apheresis (ASFA) has published practice guidelines on the use of therapeutic apheresis in the Journal of Clinical Apheresis (JCA) Special Issue. Since 2007, updated guidelines have been published every 3 years to reflect current evidence based apheresis practice with the most recent edition (8th) published in 2019. With each edition, the guidelines are reviewed and updated based on any newly published literature since the last review. The PEXIVAS study, an international, randomized controlled trial comparing therapeutic plasma exchange (TPE) vs no TPE and standard vs reduced dose steroid regimen on the primary composite outcome of end stage renal disease or death in patients with ANCA-associated vasculitis (AAV), was published in February 2020. This study represents the largest study on the role of therapeutic apheresis in AAV published to date and prompted the JCA Special Issue Writing Committee to reassess the current AAV fact sheet for updates based on this newly available evidence. This interim fact sheet summarizes current ASFA recommendations for the evidence-based use of therapeutic apheresis in AAV and supersedes the recommendations published in the 2019 guidelines.

Background Entrustable professional activities (EPAs) are well-defined, executable, observable, and measurable activities that are performed by a trainee and can be performed independently as training progresses. The purpose of this study is to develop EPAs specific for the practice of apheresis medicine (AM). Methods Members of the American Society for Apheresis Graduate Medical Education subcommittee developed a list of 28 apheresis medical activities linked to Accreditation Council for Graduate Medical Education milestones and competencies in five areas: (a) consultation, (b) clinical care for therapeutic apheresis, (c) clinical care for donor collections, (d) test optimization, and (e) vascular access. Ten AM experts using a validated tool to measure the quality of the EPAs (QUEPA) evaluated these activities with use of a Likert scale. Per group consensus, an activity was considered acceptable for each domain if it had received an average score greater than 3.7, and it was rated 4 or 5 (agree or strongly agree) by at least 70% of experts. Results Of the 28 activities, 11 did not have acceptable QUEPA scores: 7 activities were rated as unobservable, 4 were rated unfocused, 2 were rated unrealistic and not generalizable, and 2 were rated as not addressing multiple competencies. Four activities had unacceptable scores in more than one domain. Subcommittee members edited these 11 activities over two review cycles to produce a final list of 26 activities. Conclusion A set of practical, focused, and observable EPAs in AM were systematically developed. These EPAs can be used to assess and support trainee performance in AM.

Dabigatran etexilate is an oral direct thrombin (Factor IIa) inhibitor approved for patients with atrial fibrillation and for management of risk of deep vein thrombosis and pulmonary embolism. Dabigatran offers advantages over treatment with warfarin, including limited laboratory monitoring. It is equivalent in prevention of stroke and deep vein thrombosis with essentially equivalent complication rates. In contrast to warfarin, reversal of the anticoagulation is less well established. Idarucizumab is available for reversal, however supporting research is mixed; the agent also happens to be quite expensive making availability difficult. Hemodialysis has been proposed as a method of reversal, but this is difficult in patients with life threatening hemorrhage, and is not available at many hospitals. Intravenous fat emulsion (IFE) has been used for treatment of overdose of lipophilic drugs. Most toxicologists only recommend IFE for patients in extremis after ingestion of a lipid soluble substance. Dabigatran is lipid soluble, although the pro-drug more so than the active metabolite. The authors sought to see if dabigatran-induced coagulopathy of human in vitro blood samples could be reversed with IFE. Blood samples were spiked with dabigatran or dabigatran plus IFE. Values for Ecarin clot time (ECT-primary outcome), PT/INR, and aPTT, were compared across both study arms. A total of 18 healthy volunteers were included in our study. There were no significant differences in the ECT, PT/INR, and aPTT between the dabigatran arm and the dabigatran plus IFE arm. Based on these methods, IFE does not reverse dabigatran-induced coagulopathy.

Sinusoidal obstructive syndrome, also known as hepatic veno-occlusive disease, is a potentially life-threatening complication that occurs in children undergoing haemopoietic stem-cell transplantation (HSCT). Differences in the incidence of genetic predisposition and clinical presentation of sinusoidal obstructive syndrome between children and adults have rendered the historical Baltimore and Seattle diagnostic criteria insufficient for children. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) proposed the first paediatric diagnostic and severity grading guidelines for sinusoidal obstructive syndrome, intended for implementation across European centres. However, universally accepted paediatric criteria are needed to ensure prompt diagnosis, definitive treatment, and improved outcomes for children, adolescents, and young adults with sinusoidal obstructive syndrome, and to facilitate international clinical research collaboration. We convened an international panel of multidisciplinary experts including physicians with expertise in HSCT, paediatric intensive care, nephrology, hepatology, radiology, pathology, and transfusion medicine; HSCT advanced-practice providers and medical trainees; pharmacists; and translational and basic science researchers from the Pediatric Acute Lung Injury and Sepsis Investigators Network, the EBMT, the Pediatric Blood and Marrow Transplant Consortia, and several other institutions with extensive experience in sinusoidal obstructive syndrome. Panellists convened at The University of Texas, MD Anderson Cancer Center (Houston, TX, USA) in February, 2019, to evaluate the available evidence. In this expert position statement paper, we provide consensus recommendations for the international implementation of guidelines for the diagnosis, severity grading, and treatment of sinusoidal obstructive syndrome among children, adolescents, and young adults. We endorse universal adoption of paediatric diagnostic guidelines for sinusoidal obstruction syndrome as proposed by the EBMT, and provide implementation guidance for standardisation across centres; we have further proposed adjunctive use of age-appropriate organ-specific toxicity criteria for severity grading and provided prophylaxis and treatment considerations among children and adolescent and young adult patients. Key recommendations include: (1) liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of sinusoidal obstructive syndrome in children, adolescents, and young adults; (2) platelet refractoriness can be defined as a corrected count increment of less than 5000-7500 following at least two sequential ABO-compatible fresh platelet transfusions; (3) hepatomegaly is best defined as an absolute increase of at least 1 cm in liver length at the midclavicular line; and if a baseline measurement is not available, hepatomegaly can be defined as greater than 2 SDs above normal for age; and (4) the presence and volume of ascites can be categorised as mild (minimal fluid by liver, spleen, or pelvis), moderate (1 cm fluid), or severe (fluid in all three regions with1 cm fluid in at least two regions).

INTRODUCTION Indications for apheresis procedures are expanding; however, the evidence for many is low quality. A better understanding of apheresis patterns in the United States is needed to better plan prospective research studies. METHODS Data from January 1, 2013, to September 30, 2015, were analyzed from the IBM MarketScan Research Databases of de-identified health insurance claims data of several million enrollees at all levels of care from large employers and health plans across the United States. Apheresis procedures were identified by International Classification of Diseases, Ninth version (ICD-9) and Current Procedure Terminology (CPT) codes. RESULTS Combining inpatients and outpatients, 18 706 patients underwent 70 247 procedures. The patients were 52.7% female, 5.1%

INTRODUCTION Obtaining vascular access (VA) is a critical part of the therapeutic apheresis (TA) treatment plan. Currently, there are no guidelines for VA decision-making and maintenance related to TA procedures. MATERIALS AND METHODS A 28-question survey to gather qualitative information regarding VA practices was distributed to the American Society for Apheresis (ASFA) 2018 Annual Meeting attendees and all ASFA members for voluntary participation. The descriptive analyses were reported as the number and frequency of responses for each question. RESULTS Total participation was 206 with 147 (71.4%) answering some or all 16 VA focused questions. The majority of respondents were nurses or physicians (89.0%) at sites providing ≥100 procedures. The most common TA procedures were plasma exchange, red cell exchange, and leukocytapheresis. The VA evaluation was predominantly performed by the TA service (80.3%, 118/147). The majority of TA physicians and/or providers do not insert (91.7%, 132/144) or remove (81.2%, 117/143) VA catheters. When an emergent TA procedure is needed, the majority of respondents felt

OBJECTIVES To summarize current bleeding scales and their validation to assess applicability to bleeding in critically ill children. DATA SOURCES We conducted electronic searches of Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and Web of Science Core Collection databases from database inception to 2017. STUDY SELECTION Included studies contained a bleeding score, bleeding measurement tool, or clinical measurement of hemorrhage. DATA EXTRACTION We identified 2,097 unique citations; 20 full-text articles were included in the final review. DATA SYNTHESIS Of the 18 studies that included subjects (two others were expert consensus definitions), seven (39%) were pediatric-only, seven (39%) were adult-only, and four (22%) included both adults and children. Nine (50%) occurred with inpatients (two studies in critical care units), seven (39%) involved outpatients and two (11%) included both inpatients and outpatients. Thirty-nine percent of the scales were developed for those with idiopathic thrombocytopenic purpura and only two (12%) described critically ill patients. The majority (80%) included need for treatment (either RBC transfusion or surgical intervention). The majority (65%) did not report measures of reliability or validation to clinical outcomes. CONCLUSIONS There is a lack of validated bleeding scales to adequately assess bleeding and outcomes in critically ill children. Validated scales of bleeding are necessary and urgently needed.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

Background The COVID‐19 pandemic has placed additional stressors on physician lives. In this study, we report findings from a survey conducted among attending physician (AP) members of the American Society for Apheresis (ASFA) to elucidate the status of their well‐being during the COVID‐19 pandemic as well as resources provided or actions taken by their institutions and themselves personally to maintain or improve their well‐being. Study Design and Methods A 17‐question, voluntary, IRB‐approved survey regarding well‐being was distributed to the ASFA AP members between August 26, 2020 and September 16, 2020. The descriptive analyses were reported as number and frequency of respondents for each question. Non‐parametric chi‐square tests, ANOVA, and paired t‐tests were performed to determine differences in categorical variables, changes in well‐being scores, and compare time points, respectively. Results Based on the responses of 70 attending level physicians representing the United States (U.S., 53, 75.7%) and outside the U.S. (17, 24.3%), the following were observed: (1) COVID‐19 negatively affects the well‐being of a sub‐population of APs, (2) neither institutional nor individual measures to improve well‐being completely resolved the problem of decreased AP well‐being during the pandemic, and (3) personal actions may be superior to institutional resources. Conclusion There is a widespread decline in AP well‐being during the COVID‐19 pandemic that was not adequately improved by institutional or personal resources/actions taken. Institutions and physicians must work together to implement strategies including resources and actions that could further improve AP physician well‐being during a public health crisis.

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.

INTRODUCTION Performing therapeutic plasma exchange (TPE) with albumin replacement decreases coagulation factor and platelet levels. No defined guidelines exist regarding laboratory testing to assess hemostasis in patients undergoing TPE. MATERIALS AND METHODS A survey to evaluate hemostasis testing with TPE was distributed using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 120 respondents per question. Descriptive analysis was performed with results reported as the number and/or frequency (%) of respondents to each question. RESULTS The practices represented vary by institution type, number of apheresis procedures per year, and performance of TPE on children. Prior to TPE planned with albumin replacement, many respondents obtain laboratory studies for almost all patients (54.9% outpatients and 68.7% inpatients); however, some do not routinely obtain laboratory studies (9.7% outpatients and 4.4% inpatients). Hemoglobin/hematocrit, platelet count, fibrinogen, partial thromboplastin time (aPTT), and international normalized ratio (INR) are obtained prior to all TPE by 62.5%, 53.4%, 31.0%, 18.1%, and 17.7% of respondents, respectively; however, 1.0%, 8.7%, 29.0%, 38.3%, and 35.4%, respectively, do not routinely obtain these studies. Variation was observed in laboratory threshold values for action; the most common reported were hemoglobin/hematocrit reference range and >1.5 times reference range (tied, 28.1%), and INR >1.5 (20.7%). CONCLUSIONS Practice variation exists in hemostasis laboratory testing and threshold values for action with TPE. Further studies are needed to determine optimal hemostasis testing strategies with TPE.

OBJECTIVES: To present the recommendations and supporting evidence for RBC transfusions in critically ill children with hematologic and oncologic disease from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.DESIGN: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children.METHODS: The panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based clinical recommendations and research priorities for RBC transfusions in critically ill children. The hematologic/oncologic subgroup included seven experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method.RESULTS: The hematologic/oncologic subgroup developed 14 recommendations (seven clinical, seven research); all achieved greater than 80% agreement. In patients with sickle cell disease, Transfusion and Anemia Expertise Initiative recommends: 1) RBC transfusion to achieve a target hemoglobin concentration of 10 g/dL rather than hemoglobin of less than 30% prior to surgical procedures requiring general anesthesia and 2) exchange transfusion over simple (nonexchange) transfusion if the child's condition is deteriorating (based on clinical judgment), otherwise a simple, nonexchange RBC transfusion is recommended. There is insufficient evidence to make recommendations on transfusion thresholds for patients with sickle cell disease prior to minor procedures, with acute stroke or with pulmonary hypertension. For patients with oncologic disease or undergoing hematopoietic stem cell transplant, a hemoglobin concentration of 7-8 g/dL is recommended. Due to lack of evidence, research is needed to clarify the appropriate transfusion thresholds in these patients.CONCLUSIONS: Transfusion and Anemia Expertise Initiative developed specific pediatric recommendations regarding RBC transfusion management in critically ill children with sickle cell disease, oncologic disease, and hematopoietic stem cell transplant and recommendations to help guide future research priorities.

BACKGROUND Four similar transfusion reactions involving infants were reported in less than 1 year. After transfusion of red blood cells (RBCs) via syringe in the operating room, each patient experienced discolored urine, laboratory evidence of hemolysis, and acute kidney injury. Clerical and serologic investigations were unremarkable. Mechanical hemolysis was considered. STUDY DESIGN AND METHODS Simulated syringe transfusions were performed. Measurements included hematocrit (Hct), free hemoglobin, and visual hemolysis index. Washed and unwashed RBCs were tested with or without a recently introduced one-way valve, using a 24- or 16-gauge intravenous catheter. Constant manual pressure (1.43 ± 0.49 mL/sec) or syringe pump (2 mL/min) was used and a subset was timed. RESULTS The valve increased hemolysis during manual transfusion using both catheters with washed and unwashed RBCs. With the 24-gauge catheter, the change in Hct was -3.53 ± 0.69% with the valve and 0.22 ± 0.13% without (p

BACKGROUND Drug-induced immune hemolytic anemia (DIIHA) is rare, but potentially life-threatening. A high index of clinical suspicion is required for diagnosis, since the number of medications known to induce DIIHA continues to expand. Additionally, in vitro antibody reactivity against reagent additives has been reported, which may complicate test interpretation. CASE REPORT A 61-year-old group A, D+ woman with a history of negative antibody detection tests developed hemolytic anemia on Postoperative Day 7 after repeat incision and drainage of a chronically infected right knee prosthesis. She was treated with multiple antibiotics in the postoperative period, including three cephalosporins and vancomycin intravenously as well as vancomycin and gentamicin-containing intraarticular cement spacers. STUDY DESIGN AND METHODS A workup for possible DIIHA was performed. Testing was performed using vancomycin and cephalosporin antibiotics. Initially, gentamicin injection solution was used for testing, followed by testing with its component ingredients. RESULTS A vancomycin antibody was detected and anemia resolved after vancomycin was discontinued. Reactivity was seen when gentamicin injection solution was used for testing, raising the possibility of a gentamicin antibody as well. However, testing with purified gentamicin as well as methylparaben and propylparaben demonstrated a paraben antibody that reacted with the paraben-containing gentamicin solution. The patient also demonstrated an anti-N. Neither the paraben antibody nor the anti-N appeared to cause in vivo hemolysis. CONCLUSION This is the second reported case of DIIHA associated with anti-vancomycin. It is the fourth report describing a paraben antibody.

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.

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 cardiovascular surgery. Prospective studies are needed to more clearly define the role of TPE in HIT.

Acquired von Willebrand syndrome (AVWS) is a rare, potentially fatal bleeding disorder caused by low activity of von Willebrand factor (VWF) in patients without congenital deficiency. The majority of adult cases are associated with hematological malignancy, including lymphoproliferative (48%) or myeloproliferative (15%) disorders (Federici et al., 2000). Both qualitative and quantitative defects occur, due to antibody-mediated clearance or functional interference, increased proteolysis, absorption to malignant cells or platelets, or increased shear stress due to valvular defects or mechanical vascular devices (Tiede et al., 2011). The predominant mechanism for decreased or absent VWF in malignancy is autoantibodies that are inhibitory to VWF function or shorten VWF survival (Kumar et al., 2002 [3]). Antibody-mediated clearance occurs through inactivating antibody directed towards VWF, antibody binding the non-active sites of VWF, and nonspecific antibodies that form circulating immune complexes with VWF, enhancing clearance by the reticuloendothelial system (Mannucci et al., 1984). Bleeding may be very difficult to treat due to reduced half-life of VWF-concentrates.

Bleeding, a feared complication of critical illness, is frequent in critically ill children. However, the concept of clinically relevant bleeding is ill-defined in this population. There are many established diagnostic criteria for bleeding, but only one estimates bleeding in critically ill adults, and none exist for critically ill children. Our objective was to identify the factors that influence pediatric intensivists' perception of clinically relevant bleeding.Self-administered, web-based survey with 9-point Likert scales, to qualify the clinical significance of 103 bleeding characteristics in critically ill children.Online survey.Pediatric critical care physicians and nurse practitioners.None.The response rate was 40%, with 225 respondents from 16 countries. Characteristics most frequently identified as clinically relevant were bleeding in critical locations (e.g., pericardium, pleural space, CNS, and lungs); requiring interventions; leading to physiologic repercussions, including organ failure; and of prolonged duration. Quantifiable bleeding greater than 5 mL/kg/hr for more than 1 hour was frequently considered clinically relevant. Respondents identified the following characteristics as clinically irrelevant: dressings required to be changed no less frequently than every 6 hours, streaks of blood in gastric tubes, streaks of blood in endotracheal tubes or blood in endotracheal tubes only during suctioning, lightly blood-tinged urine, quantifiable bleeding less than 1 mL/kg/hr, and noncoalescing petechiae. Perception of the clinical relevance of bleeding was not associated with the respondent's geographical location of clinical practice or years of experience.This international survey provides a better understanding of the factors that influence the pediatric intensivists' assessment of the clinical relevance of bleeding in critically ill children. It provides the foundation for the development of a validated, diagnostic definition of clinically relevant bleeding in this population.

Existing literature shows mixed conclusions regarding the impact of ABO incompatibility on outcomes after hematopoietic stem cell transplantation. Because the future for umbilical cord blood (UCB) expansion technologies is bright, we assessed whether this typically overlooked graft characteristic impacted various outcomes after UCB transplantation (UCBT) for nonmalignant disorders (NMDs). A prospectively maintained institutional blood and marrow transplant program database was queried for all patients undergoing first UCBT for NMDs. UCB and recipient ABO compatibility was considered as matched, major mismatched, minor mismatched, or bidirectional mismatched. The impact of ABO incompatibility was assessed on overall survival, graft failure, acute and chronic graft-versus-host disease (GVHD), time to neutrophil and platelet recovery, day 0 to day 100 RBC transfusion burden, and donor hematopoietic chimerism. Through December 2014, 270 patients have undergone first UCBT for various NMDs. In both univariable and multivariable analyses, ABO compatibility status did not appear to impact any outcomes assessed, although a trend toward increased grades III to IV acute GVHD was seen in recipients of major mismatched units. When considering UCBT for treatment of NMDs, ABO compatibility between the donor unit and intended recipient does not appear to be an important consideration in the UCB unit choice.

Background High levels of discordance between activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-FXa) have been reported in patients with continuous-flow left ventricular assist devices (CF-LVADs). We sought to determine the biochemical basis for discordance by simultaneous measurement of coagulation factors with aPTT and anti-FXa. Methods Consecutive CF-LVAD patients admitted for intravenous unfractionated heparin (IV-UFH) therapy were studied. IV-UFH was monitored based on an anti-FXa. International normalized ratio (INR), aPTT, lactate dehydrogenase, and coagulation factors II, V, VII, VIII, IX, X, XI, and XII were measured simultaneously with anti-FXa. Results The discordance rate between anti-FXa and aPTT was 74.7% overall (568 of 760 samples from 62 patients). In samples in which coagulation factors were simultaneously measured, the discordance rate was 66% (49 of 74 samples from 52 patients). In patients with INR ≤ 1.0 the discordance level was 31.8% vs 82.7% with INR > 1.8. No difference was observed in the rate of discordance between samples with low vs normal vitamin K–dependent factors (65.9% vs 64.7%, p = 0.99). Low factor XII was found in 15%; of these, 90.9% exhibited anti-FXa/aPTT discordance. Low factor V was found in 8.2%, and all were discordant. Factor VIII was elevated in 97% of samples, and 65.7% were discordant. Conclusions In addition to the effects of warfarin administration on aPTT, the influence of other factors, such as low factor XII or V, may contribute to the discordance between aPTT values and anti-FXa. Coagulation factor levels may assist in individualization of anti-coagulation targets while patients implanted with CF-LVADs are on IV-UFH.

Background: The balance of hemostasis and anticoagulation is a concern for patients dependent upon ventricular assist devices (VADs). Bleeding is a common complication with both short- and long-term use of these devices. A better understanding of the risk factors and etiologies of bleeding associated with these devices is needed and could improve the overall results. We sought to determine the relationship of mechanical circulatory assist device use with acquired von Willebrand disease (avWD) in children. Methods: Data were analyzed retrospectively via review of the medical record of 19 consecutive patients who were supported with the Berlin EXCOR VAD for greater than 24 hours. Laboratory testing for avWD was performed at the discretion of the clinical team, often in association with clinical bleeding. Results: Of 19 pediatric patients, 10 (52.6%) had laboratory testing consistent with avWD. Median time to detection of avWD was 35 days postimplantation of device (range 0-310 days). Both minor mucosal bleeding and bleeding requiring intervention were highly prevalent in patients in whom avWD was identified (10/10 [100%] and 7/10 [70%]). The mean age of all patients was 3.3 years, but patients found to have avWD tended to be older (mean 5.3 years) and supported with larger volume VADs. Conclusions: This experience demonstrates a high prevalence of avWD following EXCOR implantation. Bleeding, older age, and larger VAD size may be associated with avWD. These results should stimulate critical evaluation of individualized anticoagulation regimens in pediatric VAD patients.

Rivaroxaban and dabigatran are among the newest anticoagulants, and measuring their concentration in patients is a new challenge for clinical laboratories. We analyzed data from the ECAT proficiency program to determine how well the assays are performing in clinical laboratories internationally. Most laboratories received a passing grade (Z score

Background Therapeutic plasma exchange (TPE) may remove medications from the patient's plasma. Data is limited on the effect of TPE on unfractionated heparin (UFH). Study design and methods A retrospective review was performed of patients receiving TPE and continuous IV infusion UFH from 1/1/2008 to 6/30/2010. TPE with plasma or 5% albumin for replacement fluid and pre and post anti-Xa levels within approximately six hours were analyzed. Results Three patients had 15 TPE with plasma replacement. Anti-Xa levels decreased 47% (mean, -0.25 IU/mL) for two TPE when UFH was not changed, 78% (-0.35 IU/mL) for one TPE when the UFH rate was decreased 25%; and 61% (mean -0.72 IU/mL) for two single volume TPE and 87% (-0.65 IU/mL) for one 1.5 plasma volume TPE when UFH was stopped. During nine TPE, the UFH rate was increased by 65% resulting in a mean increase in the anti-Xa level (mean 0.06 IU/mL, 30%). One patient had five single plasma volume TPE with 5% albumin. Anti-Xa levels decreased when the UFH was not changed (-0.06 IU/mL, 38%) and increased when UFH was increased by 30% (0.19 IU/mL, 61%) and 69% (mean 0.04 IU/mL, 15% in three TPE). The PTT increased with all albumin procedures, with more marked increases observed when the UFH rate was increased, while the antithrombin level decreased (mean 65%). Conclusion Heparin was removed from the patient's plasma during TPE. Adjustment of the dose during TPE may be necessary to maintain therapeutic drug levels. Methods for monitoring UFH therapy may not agree. J. Clin. Apheresis 31:507-515, 2016. © 2016 Wiley Periodicals, Inc.

SummaryIn 2010–2012, the North American Specialized Coagulation Laboratory Association (NASCOLA) distributed 12 proficiency testing challenges to evaluate laboratory testing for protein S (PS). Results were analysed to assess the performance of PS activity, PS free antigen, and PS total antigen testing. Statistical analysis was performed on the numeric results and qualitative classification submitted for each method. There were 2,106 total results: 716 results from PS activity assays, 833 results from PS free antigen assays, and 557 results from PS total antigen assays. The three assay types performed well in the classification of five normal samples and nine abnormal samples, although certain PS activity methods were more likely to classify normal samples as abnormal and one PS total antigen assay was more likely to classify abnormal samples as normal. PS activity methods were affected by interfering substances such as heterozygous or homozygous factor V Leiden mutation (underestimation) and the anticoagulant drug rivaroxaban (overestimation). In conclusion, NASCOLA laboratories using a variety of PS assays performed well in the classification of clearly normal and abnormal samples. Laboratories performing PS activity assays should be aware of potential interferences in samples positive for FV Leiden or containing certain anticoagulant medications.

OBJECTIVES: To present the recommendations and supporting literature for selection and processing of RBC products in critically ill children developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.DESIGN: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children METHODS:: The panel of 38 experts developed evidence-based, and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The RBC processing subgroup included five experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method.RESULTS: Five recommendations reached agreement (> 80%). Irradiated cellular products are recommended for children at risk of transfusion-associated graft versus host disease due to severe congenital or acquired causes of immune deficiency or when the blood donor is a blood relative. Washed cellular blood components and avoidance of other plasma-containing products are recommended for critically ill children with history of severe allergic reactions or anaphylaxis to blood transfusions, although patient factors appear to be important in the pathogenesis of reactions. For children with history of severe allergic transfusion reactions, evaluation for allergic stigmata prior to transfusion is recommended. In children with severe immunoglobulin A deficiency with evidence of antiimmunoglobulin A antibodies and/or a history of a severe transfusion reaction, immunoglobulin A-deficient blood components obtained either from an immunoglobulin A-deficient donor and/or washed cellular components is recommended.CONCLUSIONS: The Transfusion and Anemia Expertise Initiative consensus conference developed recommendations for selection and processing of RBC units for critically ill children. Recommendations in this area are largely based on pediatric and adult case report data.

Storage of platelets at 4°C compared with 22°C may increase both hemostatic activity and storage duration; however, the maximum duration of cold storage is unknown. We report the design of an innovative, prospective, randomized, Bayesian adaptive, "duration finding" clinical trial to evaluate the efficacy and maximum duration of storage of platelets at 4°C.Patients undergoing cardiac surgery and requiring platelet transfusions will be enrolled. Patients will be randomized to receive platelets stored at 22°C up to 5 days or platelets stored at 4°C up to 5 days, 10 days, or 15 days. Longer durations of cold storage will only be used if shorter durations at 4°C appear noninferior to standard storage, based on a four-level clinical hemostatic efficacy score with a NIM of a half level. A Bayesian linear model is used to estimate the hemostatic efficacy of platelet transfusions based on the actual duration of storage at 4°C.The type I error rate, if platelets stored at 4°C are inferior, is 0.0247 with an 82% probability of early stopping for futility. With a maximum sample size of 1,500, the adaptive trial design has a power of over 90% to detect noninferiority and a high probability of correctly identifying the maximum duration of storage at 4°C that is noninferior to 22°C.An adaptive, duration-finding trial design will generate Level I evidence and allow the determination of the maximum duration platelet storage at 4°C that is noninferior to standard storage at 22°C, with respect to hemostatic efficacy. The adaptive trial design helps to ensure that longer cold storage durations are only explored once substantial supportive data are available for the shorter duration(s) and that the trial stops early if continuation is likely to be futile.

BACKGROUND Patients undergoing therapeutic plasma exchange (TPE) may present with risks for hemorrhage or thrombosis. Use of replacement fluids devoid of coagulation factors will decrease factor levels and platelet levels. There are no established guidelines for hemostasis management in these situations. MATERIALS AND METHODS A survey to evaluate current hemostasis management practice during TPE was conducted using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 107 respondents. Descriptive analysis was performed with results reported as the number and frequency (%) of respondents to each question. RESULTS Apheresis Medicine physicians, alone (59.4%) or jointly with the requesting provider (29.2%), choose the replacement fluid. Based on a theoretical patient case receiving five TPEs approximately every other day, the percent of respondents who would use albumin with or without normal saline was 94.7% with no history of a bleeding or clotting disorder, 1.1% with active bleeding, and 8.8% with hypofibrinogenemia (

Four similar transfusion reactions involving infants were reported in less than 1 year. After transfusion of red blood cells (RBCs) via syringe in the operating room, each patient experienced discolored urine, laboratory evidence of hemolysis, and acute kidney injury. Clerical and serologic investigations were unremarkable. Mechanical hemolysis was considered.Simulated syringe transfusions were performed. Measurements included hematocrit (Hct), free hemoglobin, and visual hemolysis index. Washed and unwashed RBCs were tested with or without a recently introduced one-way valve, using a 24- or 16-gauge intravenous catheter. Constant manual pressure (1.43 ± 0.49 mL/sec) or syringe pump (2 mL/min) was used and a subset was timed.The valve increased hemolysis during manual transfusion using both catheters with washed and unwashed RBCs. With the 24-gauge catheter, the change in Hct was -3.53 ± 0.69% with the valve and 0.22 ± 0.13% without (p 0.00001). Comparing the individual valves tested, differences in hemolysis were observed (change in Hct, p 0.0001). During manual transfusion with 24-gauge catheter and unwashed RBCs, the degree of hemolysis was greater when it took longer to transfuse with a valve (change in Hct versus time, r = -0.75, p 0.0001) compared to a slight increase in hemolysis for samples that took less time to transfuse without a valve (change in Hct versus time, r = 0.58, p = 0.23).Mechanical hemolysis should be considered when investigating possible hemolytic transfusion reactions, especially with high rates of transfusion and use of a valve. During rapid manual transfusion with the valve, greater resistance was associated with increased hemolysis.

The international normalized ratio (INR) can be unreliable in patients with lupus anticoagulants (LACs) or other conditions affecting baseline testing. Alternative methods to assess anticoagulation on warfarin through measures of vitamin K-dependent factor activity by clot based or chromogenic assays may be necessary. In this patient population, the ideal method is unknown. Thirty-six patients stable on warfarin with LAC or unreliable INR testing had an INR, a prothrombin time-based clotting assay for factor II (FII) activity, and a chromogenic assay for factor X (CFX) activity were performed simultaneously. Eighty-nine sets of measurements were obtained of which 83 sets included all three assays. CFX and FII levels were well correlated (r = 0.92) in all patients and in 26 patients with a documented antiphospholipid antibody (r = 0.93). Parallel testing was seen in 99% of FII assays. Sixty-one percent of CFX and 57% of FII were within the therapeutic range. In 32 CFX and FII pairs wherein assessment of anticoagulation was discordant, 16 CFX agreed with INR and 13 FII agreed with INR (McNemar's, χ = 0.14, P = 0.7). The number of times tests were discrepant was not statistically different between CFX and FII (P = 0.36). CFX and FII activity are well correlated in patients that require alternative monitoring of warfarin. Either test can be used in this population.

Neuromyelitis optica (NMO) is a relapsing inflammatory disease of the central nervous system that predominantly affects the spinal cord and optic nerves. The clinical hallmark of the disease is a step-wise deterioration of visual and spinal cord function. This study reviews patients with steroid resistant relapsing NMO presenting for therapeutic plasma exchange (TPE) at our institution from December 2005 to December 2012. A total of five patients were treated with single volume TPE. Both subjective and objective clinical response to TPE was estimated by three different sources (the patient, a Transfusion Medicine physician, and the treating Neurologist) with the patient and Transfusion Medicine physician's final assessment of response made at the time of the last TPE in the series and the treating neurologist's assessment of response made at the time of the next neurological exam after the last TPE. A total of 17 TPE series were performed with the average course of therapy being three series (ranged 1–5) with five TPE (ranged 3–7) per series. All patients demonstrated improvement with each series of TPE and all procedures were well tolerated with only transient and well-described reactions all of which were successfully resolved with minor or no sequelae. J. Clin. Apheresis 29:171–177, 2014. © 2013 Wiley Periodicals, Inc.

Therapeutic plasma exchange (TPE) without plasma replacement results in coagulation factor removal. Warfarin decreases the activity of vitamin K dependent coagulation factors. The combined effect of TPE and warfarin on the coagulation system has not been studied. A prospective, observational study was conducted in patients undergoing TPE while on warfarin. One plasma volume TPEs were performed on the COBE Spectra Apheresis System (Terumo BCT, Lakewood, CO) with 5% albumin. International normalized ratio (INR), fibrinogen, and factor II activity were obtained pre and post procedure. Eight patients underwent 121 TPEs that met study criteria with pre and post data. The average pre values were INR 2.09 ± 0.58, fibrinogen 263 ± 76 mg/dl, and factor II 29 ± 16% and the average post values were INR 4.12 ± 1.44, fibrinogen 105 ± 31 mg/dl, and factor II 13 ± 7%. The pre-INR was ≥2.00 for 55% of TPEs. The pre value (Y0) predicts the post value (Y) by the following equations Y = −0.54 + 2.21Y0, Y =12.10 + 0.35Y0, and Y =1.83 + 0.39Y0 for INR, fibrinogen, and factor II respectively. In conclusion, pre procedure laboratory values can predict the post laboratory values for patients on warfarin receiving single plasma volume TPE with albumin replacement. The post-INR is approximately twice the pre-INR. At normal and mildly elevated pre-INR, the effect of TPE on the INR is less marked. A single plasma volume TPE decreases the plasma level by ∼65% for fibrinogen and 60% for factor II. J. Clin. Apheresis 29:75–82, 2014. © 2013 Wiley Periodicals, Inc.

Aspirin (ASA) is recommended for the prevention of cardiovascular disease; however, the compliance is low. Reported use may not reflect actual use. Serum thromboxane B2 (STxB2) measurement was evaluated to validate reported ASA use. Males aged 45 to 79 years and females aged 55 to 79 years completed a survey and STxB2 measurement (Thromboxane B2 EIA Kit; Cayman Chemical, Ann Arbor, Michigan). The 107 patients were grouped by use of ASA (56 ASA+ and 51 ASA−) and possible interfering medications (INT) such as nonsteroidal anti-inflammatory drugs. The STxB2 levels (ng/mL) were significantly lower in ASA users: ASA+ INT− 3.0 (0.7, 8.4), ASA+ INT+ 2.0 (0.8, 4.9), ASA− INT+ 176 (75, 390), and ASA− INT− 271 (199, 366). The INT use did not cause a significant difference in STxB2 levels. A STxB2 cut point of 25 ng/mL had high sensitivity (94.1%) and specificity (91.1%) for ASA use. The STxB2 was a reliable marker of ASA use and could be used to confirm ASA exposure in population-based health studies.

To assess the state of current practice in coagulation laboratories regarding three pressing issues: staffing, handling Ebola specimens, and testing/billing for tests that measure direct oral anticoagulants (DOAC).A survey and analysis of specialized coagulation laboratories in North America was conducted.Approximately 4,000 special coagulation tests-per-technologist-per-year was rated as either a "good" staffing level or "adequate-but-ideally-need-more" employees. Requiring technologists to perform more than that was rated as an "inadequate" staffing level. For Ebola patients, coagulation testing is mostly performed by point-of-care. Only 26.1% would perform coagulation tests for Ebola specimens within their laboratory (rather than at the bed side or a separate designated space outside the laboratory). Coagulation tests offered for Ebola patients were limited: prothrombin time (63.0% of laboratories), activated partial thromboplastin time (37.0%), D-dimer (13.0%), and fibrinogen (8.7%); 26.1% of laboratories did not offer any coagulation tests for Ebola patients. Approximately 35% of special coagulation laboratories bill for at least one laboratory test for DOACs: 33% bill for an anti-Xa calibrated with rivaroxaban, 17% bill for an anti-Xa calibrated with apixaban, and 27% bill for at least one of several tests for dabigatran. Approximately 48% do not offer any tests for DOACs.These results may help laboratories negotiate for additional technologists if needed, prepare for Ebola specimens, and manage the demand for laboratory tests for new DOAC anticoagulants.

Rivaroxaban and dabigatran are among the newest anticoagulants, and measuring their concentration in patients is a new challenge for clinical laboratories. We analyzed data from the ECAT proficiency program to determine how well the assays are performing in clinical laboratories internationally. Most laboratories received a passing grade (Z score3) for the results of their dabigatran and rivaroxaban testing. Failing Z scores were not associated with any particular method. With dabigatran, some homemade calibrators gave higher results than the commercially available calibrators. There were no significant differences among the instruments or the 5 reagents in use, but results showed inter-laboratory variability that could have clinical significance. The 3 reagents with the lowest number of users had poor inter-laboratory precision. Ten different anti-Xa reagents were in use for rivaroxaban testing. One reagent gave lower results than other reagents at 100 ng/mL but not at 300 ng/mL. There were no significant differences among the different rivaroxaban calibrators or instruments. In conclusion, inter-laboratory precision could be improved for both dabigatran and rivaroxaban assays. Homemade dabigatran calibrators differed from commercially available calibrators, and there was a statistically significant difference between some of the rivaroxaban reagents. About 10% of results received failing Z scores or passed but fell in a range that require the laboratory to investigate for bias or other inaccuracy in their method. Am. J. Hematol. 91:E464-E467, 2016. © 2016 Wiley Periodicals, Inc.

Platelets play a crucial role in the pathogenesis of atherosclerosis, thrombosis, and stroke. Aspirin used alone or in combination with other antiplatelet drugs has been shown to offer significant benefit to patients at high risk of vascular events. Resistance to the action of aspirin may decrease this benefit. Aspirin resistance has been defined by clinical and/or laboratory criteria; however, detection by laboratory methods prior to experiencing a clinical event will likely provide the greatest opportunity for intervention. Numerous laboratory methods with different cutoff points have been used to evaluate the resistance. Noncompliance with aspirin treatment has also confounded studies. A single assay is currently insufficient to establish resistance. Combinations of results to confirm compliance and platelet inhibition may identify "at-risk" individuals who truly have aspirin resistance. The most effective strategy for managing patients with aspirin resistance is unknown; however, studies are currently underway to address this issue.

Wilson's disease (WD) is an autosomal-recessive disorder of impaired copper metabolism resulting in accumulation of copper primarily in the liver but ultimately in many organs and tissues. A small number of patients with WD initially present with fulminant hepatic failure (FHF), hypercupremia, and intravascular hemolysis. The therapeutic goals for these patients include quickly removing the copper and preparing the patient for liver transplantation. Here, we report on a 6-year-old male with WD in FHF with anemia, renal insufficiency, and coagulopathy. The patient received a series of therapeutic plasma exchanges (TPE) as adjunctive therapy to remove copper and stabilize his coagulopathy and anemia until a transplant was possible. A total of five single plasma volume (1500 mL) TPE were performed over the course of 11 days with plasma as the replacement fluid. Laboratory results demonstrated temporary improvement after each procedure. Liver transplantation was performed 12 days after beginning TPE and 35 days after admission to the hospital. TPE was a successful adjunctive therapy to bridge this patient with WD to transplantation.

Background Daily low‐dose aspirin is recommended for primary prevention of myocardial infarction and stroke in higher‐risk patients. Population trends in aspirin use for cardiovascular disease (CVD) prevention in an urban population (Minneapolis/St. Paul, 2010 population 2.85 million) from 1980 to 2009 were evaluated. Methods and Results Surveys of randomly selected adults aged 25 to 74 years were collected at 5‐year intervals. Self‐reports of regular aspirin use for CVD prevention and history of CVD were obtained. Six cross‐sectional surveys included 12 281 men and 14 258 women. Age‐adjusted aspirin use for primary prevention increased during this period from 1% to 21% among men and 1% to 12% among women. Aspirin use was highest in those aged 65 to 74 years. For secondary prevention, age‐adjusted aspirin use increased from 19% to 74% among men and 11% to 64% among women. While data are based on self‐report, a substudy using a biochemical indicator of aspirin use (serum thromboxane B 2 ) supports the validity of self‐report. Conclusions Aspirin for CVD prevention is commonly used by a large and growing portion of the general population. It is not known if this is based on professional advice or self‐prescribed use. It is also likely that many who would benefit do not use aspirin and others use aspirin inappropriately.

BACKGROUND: Bacterial contamination is currently the most important infectious risk associated with transfusion of platelet (PLT) products. Prestorage culture has reduced but not eliminated this problem. STUDY DESIGN AND METHODS: Eighteen hospitals studied the Pan Genera Detection (PGD) test, a rapid, lateral-flow immunoassay for the detection of Gram-positive and Gram-negative bacteria. The PGD test was performed on day of issue on apheresis PLTs released by collection centers as culture negative. Confirmatory bacterial culture was performed when PGD tests were repeatedly reactive, with three sites performing culture on all doses studied. RESULTS: PGD tests on nine of 27,620 (1:3069, 95% confidence interval [CI] 1:6711 to 1:1617; or 326 per million, 95% CI 149-618 per million) apheresis PLT doses were repeatedly reactive and verified as bacterially contaminated by confirmatory culture. Bacterial species isolated included coagulase-negative staphylococci (n = 6), Bacillus sp. (n = 2), and Enterococcus faecalis (n = 1). The ages of these contaminated doses were Day 3 (n = 4), Day 4 (n = 2), and Day 5 (n = 3). Two contaminated doses with nonreactive PGD tests were detected among 10,424 doses at hospitals where concurrent culture was performed, and one other was identified via a transfusion reaction investigation. There were 142 PGD false positives (0.51%). CONCLUSIONS: The PGD test detected bacterial contamination in 1:3069 (9 of 27,620) doses released as negative by prestorage culture in PLTs as young as 3 days old. Three contaminated doses, two clinically insignificant, had nonreactive PGD tests, while 0.51% of tests were false positives. Application of this test on day of issue can interdict contaminated units and prevent transfusion reactions.

BACKGROUND: Acute hemorrhagic leukoencephalitis (AHLE) is a rare, fatal, central nervous demyelinating disease characterized by a rapid fulminant clinical course. Successful management requires early diagnosis, aggressive management of cerebral edema, and immunosuppression. Therapeutic plasma exchange (TPE) is infrequently used and commences after initial management fails. CASE REPORT: A 31-year-old man presented with right arm weakness, whose symptoms rapidly progressed to hemiplegia and aphasia. The patient was initially managed with glucocorticosteroids. Decompressive craniotomy and brain biopsies were performed when his intracranial pressure increased. Brain biopsy findings were consistent with AHLE. Mycoplasma pneumonia immunoglobulin G and immunoglobulin M serologies revealed recent infection. Despite surgical and medical management, he decompensated on Day 11, and TPE was initiated. The patient received a total of 10 TPE treatments. On the fourth day of TPE treatment, he was extubated. Twenty-one days after TPE began, he was ambulating with near normal muscle strength and was discharged. Four months after initial presentation, the patient has normal strength and is working full-time. CONCLUSIONS: AHLE has a fulminant course requiring accurate and rapid diagnosis. Successful therapy requires aggressive management of intracranial pressure and immunosuppression. Two other reports of AHLE document successful management with TPE. Each of these patients survived with minimal neurologic impairments. Given the likely immune-mediated nature of this disease, combined treatment of steroids, surgery, and TPE may lead to shorter hospital stays and improved neurologic outcomes. Clinical studies are needed to further study the effect of TPE on neurologic outcome in AHLE.

Therapeutic plasma exchange (TPE) may remove medications from the patient's plasma. Data is limited on the effect of TPE on unfractionated heparin (UFH).A retrospective review was performed of patients receiving TPE and continuous IV infusion UFH from 1/1/2008 to 6/30/2010. TPE with plasma or 5% albumin for replacement fluid and pre and post anti-Xa levels within approximately six hours were analyzed.Three patients had 15 TPE with plasma replacement. Anti-Xa levels decreased 47% (mean, -0.25 IU/mL) for two TPE when UFH was not changed, 78% (-0.35 IU/mL) for one TPE when the UFH rate was decreased 25%; and 61% (mean -0.72 IU/mL) for two single volume TPE and 87% (-0.65 IU/mL) for one 1.5 plasma volume TPE when UFH was stopped. During nine TPE, the UFH rate was increased by 65% resulting in a mean increase in the anti-Xa level (mean 0.06 IU/mL, 30%). One patient had five single plasma volume TPE with 5% albumin. Anti-Xa levels decreased when the UFH was not changed (-0.06 IU/mL, 38%) and increased when UFH was increased by 30% (0.19 IU/mL, 61%) and 69% (mean 0.04 IU/mL, 15% in three TPE). The PTT increased with all albumin procedures, with more marked increases observed when the UFH rate was increased, while the antithrombin level decreased (mean 65%).Heparin was removed from the patient's plasma during TPE. Adjustment of the dose during TPE may be necessary to maintain therapeutic drug levels. Methods for monitoring UFH therapy may not agree. J. Clin. Apheresis 31:507-515, 2016. © 2016 Wiley Periodicals, Inc.