Granulocyte Transfusion: Clinical Updates and a Practical Approach to Transfusion.

Neutrophils are an integral component of the innate immune system and key regulators of cell-mediated defense against bacterial and fungal pathogens. The potential of granulocyte transfusions has been investigated to temporarily replenish innate immune function to prevent and/or treat infections in patients with severe neutropenia or neutrophil dysfunction. However, evidence has been largely theoretical, experimental, and/or inconclusive. Clinical efficacy has yet to be confirmed by large-scale randomized controlled clinical trials. Performing such trials has been hampered by low granulocyte collection yield and poor patient accrual. We provide a practical summary of the current literature surrounding the practice of granulocyte transfusion.

Coping With COVID-19.

OBJECTIVES: The first coronavirus disease 2019 (COVID-19) case in the United States was reported in Washington State. The pandemic caused drastic disruptions to medical institutions, including medical education. The Department of Laboratory Medicine at the University of Washington responded by rapidly implementing substantial changes to medical student clerkships. METHODS: In real time, we converted one ongoing case- and didactic-based course, LabM 685, to remote learning. RESULTS: Fifteen of 17 scheduled sessions proceeded as planned, including two sessions for student presentations. Two didactics were canceled as the functions of the teleconferencing platform were not sufficient to proceed. One grand rounds speaker canceled due to COVID-19 precautions. Elements of an immersive clinical laboratory clerkship, LabM 680, were repurposed to accommodate 40 medical students per class via remote learning, highlighting clinical laboratory activities that continue throughout the outbreak. A new remote clerkship, MedSci 585C, was developed incorporating distance learning and guided small-group sessions. This coincided with parallel efforts to make resident and fellow service work, conferences, and didactics available remotely to comply with social distancing. CONCLUSIONS: The changes in medical education described reflect the dynamic interplay of current events affecting the world of clinical pathology. Throughout this, technology-while with some limitations-has provided the platform for innovative learning.

Laboratory Assay Evaluation Demystified: A Review of Key Factors Influencing Interpretation of Test Results Using Different Assays for SARS-CoV-2 Infection Diagnosis.

Laboratory tests are an integral part of the diagnosis and management of patients; however, these tests are far from perfect. Their imperfections can be due to patient health condition, specimen collection, and/or technological difficulty with performing the assay and/or interpretation. To be useful clinically, testing requires calculation of positive predictive values (PPVs) and negative predictive values (NPVs). During the current global pandemic of COVID-19 (coronavirus disease 2019), multiple assays with unknown clinical sensitivity and specificity have been rapidly developed to aid in the diagnosis of the disease. Due to a lack of surveillance testing, the prevalence of COVID-19 remains unknown. Hence, using this situation as an clinical example, the goal of this article is to clarify the key factors that influence the PPV and NPV yielded by diagnostic testing, By doing so, we hope to offer health-care providers information that will help them better understand the potential implications of utilizing these test results in clinical patient management.

An Automated Method for Direct Antiglobulin Testing and the Resulting Amount of Phototherapy Used at a Large Academic Medical Center.

OBJECTIVE: To evaluate how clinical practice was affected by the change in direct antiglobulin testing (DAT) methodologies and subsequent stronger reported DAT results at our large academic medical center. METHOD: We retrospectively reviewed DAT results of umbilical cord blood from infants with blood type A or B born to mothers with antibody-negative type O blood, based on records kept at the University of Alabama at Birmingham (UAB) Hospital, a 1400-bed academic medical center. RESULTS: We randomly chose 50 neonates with positive DAT results who had been tested using the tube method and 50 whose testing had used the gel method. Although 86% of results with the tube method were positive microscopically, 52% and 40% of the DAT results with the gel method were 1+ and 2+ positive, respectively. Further, we observed an increase in the number of neonates treated with phototherapy who had been tested using the gel method. CONCLUSION: We report that DATs performed using the gel method had increased DAT strength compared with tube testing, which led to increased use of phototherapy by our clinical colleagues.

Frequency of Alterations in Apheresis-Related Abstracts Prior to Publications as Peer-Reviewed Articles.

High-quality evidence supporting clinical practice is lacking in apheresis. A potential source of evidence is provided by abstracts submitted to the Annual Meetings of the American Association of Blood Banks (AABB) and the American Society for Apheresis (ASFA). However, there is potential for study conclusions to be altered significantly following abstract presentations prior to publications in peer-reviewed journals. Therefore, we evaluated the discordance rate between apheresis-related meeting abstracts and their corresponding published articles. Abstracts accepted to either AABB or ASFA Annual Meetings from 2005 to 2012 and corresponding PubMed-indexed peer-reviewed articles' abstracts published prior to 9/2014 were reviewed for altered methods, results, and conclusions. When present, changes were evaluated for clinical significance. During the 8-year period, 198 out of 1152 abstracts were published as peer-reviewed articles. Of these, 36 (18.2%) presented discordant results, six of which (16.7%) were potentially clinically significant. An alteration in results (58.3%) was the leading reason for discordance. The discordance rate for ASFA abstracts was significantly higher (HR = 4.69, P = 0.0028) than the AABB ones. However, clinically significant alterations occurred more frequently among AABB abstracts (P = 0.025). Approximately 18% of meeting abstracts demonstrated alterations prior to publication in peer-reviewed journals. Given that approximately one in six changes represented clinically significant alterations, potentially affecting clinical practice, we recommend caution when modifying one's clinical practice based on abstract presentations at Annual Meetings. Future studies involving abstracts from both the International Society for Apheresis and the World Apheresis Association should also be performed.

A brief review of common mathematical calculations in therapeutic apheresis.

Apheresis is defined as the removal of blood from the body, its separation into constituent components, and removal or manipulation of one of these components prior to intravascular return with or without the addition of replacement fluid. Patients undergoing therapeutic apheresis often have multiple comorbidities, potentially affecting their hemodynamic status. Thus, a thorough understanding of apheresis principles and calculations is required for the performance of safe, efficacious, and successful procedures. The performance of simple transfusions or red blood cell exchange procedures is additionally complicated by the difficulties inherent in the procurement of compatible blood products, and the emphasis on minimizing exposure to unnecessary blood products. It is essential that apheresis physicians be able to accurately evaluate the risks/benefits inherent in the procedural options and efficiently stratify patients to the optimal therapeutic modality. The formulas requisite for performing therapeutic apheresis calculations are herein reviewed.

Therapeutic plasma exchange - A brief review of indications, urgency, schedule, and technical aspects.

The American Society for Apheresis (ASFA) regularly publishes evidence-based guidelines, with the most recent edition in 2016, to assist the requesting and/or apheresis physicians with the evaluation of therapeutic apheresis. Given that therapeutic plasma exchange (TPE) is one of the most common therapeutic apheresis procedures, in this review, we discuss the rationale of TPE in both ASFA category I (first-line therapy) and II (second-line therapy) indications. However, the ASFA Guidelines usually provide little guidance with regard to scheduling/urgency issues. Given that mobilizing resources to perform apheresis after-hours may be expensive and challenging, we classified the urgency of the procedures in this review into 3 distinct groups: emergent (i.e. TPE should be started as soon as possible, preferably within 4-6 h upon request), urgent (i.e. TPE should be initiated within 24 h of request), and routine (i.e. TPE may be performed during regular working hours) based on our experiences in clinical practices. A brief discussion of the technical aspects as well as important considerations for an apheresis consultation is also provided.

CD5 positive B-ALL, a uniquely aggressive subcategory of B-ALL? A case report and brief review of the literature.

CD5 antigen expression in B-cell acute lymphoblastic leukemia (B-ALL) is exceptionally rare. There are six detailed case reports in the literature, with only 16 cases described. Case series analyzing the frequency of aberrant B-ALL immunophenotypes suggest that this variant may occur in as little as 2-4.5% of all B-ALL cases, with one series having no CD5+ positive cases. Herein we report a case of CD5+ B-ALL in a 15-year-old female, and review the previously reported cases. As limited information is available, more data from prospective clinical trials are required to determine whether CD5 positivity portends a poorer prognosis.

N-Methyl-d-aspartate Receptor Antibody Encephalitis: A Concise Review of the Disorder, Diagnosis, and Management.

Anti-NMDA ( N-methyl-d-aspartate) receptor (anti-NMDAR) encephalitis is one of the most common paraneoplastic encephalitides. It occurs in both sexes, across all age ranges, and may occur in the presence or absence of an associated tumor. Its pathogenesis and clinical presentation relate to the presence of IgG1 or IgG3 antibodies targeting the NR1 subunit of the NMDA receptor, leading to a disinhibition of neuronal excitatory pathways. Initial clinical manifestations may be nonspecific, resembling a viral-like illness; however, with disease progression, symptoms can become quite severe, including prominent psychiatric features, cognitive problems, motor dysfunction, and autonomic instability. Anti-NMDAR encephalitis may even result in death in severe untreated cases. Diagnosis can be challenging, given that initial laboratory and radiographic results are typically nonspecific. The majority of patients respond to first or second-line treatments, although therapeutic options remain limited, usually consisting of tumor removal (if there is confirmation of an underlying malignancy) in conjunction with prompt initiation of immunosuppressive medications along with intravenous immunoglobulins and/or plasma exchange. Although the clinical presentation of anti-NMDAR encephalitis overlaps with several other more common neurological and psychiatric disorders, early diagnosis and treatment is essential for a positive prognosis. Here, we concisely review the pathogenesis, diagnosis, and clinical management of this disease.

Monitoring Fondaparinux in the Setting of Antithrombin Deficiency.

Heparin-induced thrombocytopenia (HIT) is a not-uncommon adverse effect of heparin exposure, with potentially serious and/or fatal thrombotic consequences. Recent studies looking at the off-label use of fondaparinux for HIT show similar efficacy and adverse-effect profiles, as well as improved costs, compared with some commonly used direct thrombin inhibitors. Although routine laboratory monitoring of fondaparinux-specific anti-Xa levels typically is not recommended, we present a case report that suggests fondaparinux monitoring may be needed in patients with hepatic impairment causing acquired antithrombin deficiency. We performed daily assessment of antithrombin- and fondaparinux-specific anti-Xa levels in a 50-year-old female of unknown ethnicity to ensure that fondaparinux dosing was maintained within an acceptable range. With this management strategy, the patient experienced no thrombotic or hemorrhagic complications during the hospital admission or the following 2 months in outpatient treatment.

Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura.

Immune-mediated thrombotic thrombocytopenic purpura is characterized by severe thrombocytopenia and microangiopathic hemolytic anemia. It is primarily caused by immunoglobin G type autoantibodies against ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. However, reliable markers predictive of patient outcomes are yet to be identified. Seventy-three unique patients with a confirmed diagnosis of immune-mediated thrombotic thrombocytopenic purpura between April 2006 and December 2017 were enrolled from the Univeristy of Alabama at Birmingham Medical Center. Clinical information, laboratory values, and a panel of special biomarkers were collected and/or determined. The results demonstrated that the biomarkers associated with endothelial injury (e.g., von Willebrand factor antigen and collagen-binding activity), acute inflammation (e.g., human neutrophil peptides 1-3 and histone/deoxyribonucleic acid complexes), and activation of the complement alternative pathway (e.g., factors Bb and iC3b) were all significantly increased in patients with acute immune-mediated thrombotic thrombocytopenic purpura compared to those in the healthy controls. Moreover, failure to normalize platelet counts within 7 days or failure to markedly reduce serum lactate dehydrogenase by day 5, low total serum protein or albumin, and high serum troponin levels were also predictive of mortality, as were the prolonged activated partial thromboplastin time, high fibrinogen, and elevated serum lactate dehydrogenase, Bb, and sC5b-9 on admission. These results may help to stratify patients for more intensive management. The findings may also provide a framework for future multicenter studies to identify valuable prognostic markers for immune-mediated thrombotic thrombocytopenic purpura.

Debunking superstition: Analyzing the cloud phenomenon in apheresis-Results of a 35-month study.

Many practitioners believe in the phenomenon of being labeled either a "black cloud" or "white cloud" while on-call. A "white-cloud" physician is usually defined as one who sees fewer cases while a "black-cloud" is one who often receives more cases. To evaluate these phenomena, a 35-month prospective study was designed to evaluate the number of times apheresis staff was involved with emergent apheresis procedures at a large institution in the off hours between 10 pm and 7 am, since this is the time period when significant resources have to be mobilized to perform the procedure. During the study period, 92 emergent procedures (or "black-cloud" events, 8.6%) occurred. The median time between two consecutive "black-cloud" events was 9 days (range: 1-45 days). We found that there is no statistically significant association between the occurrence of "black-cloud" events and attending physicians (P = .99), nurses who had 56 or more days on-call during the course of the study (P = .28), year (P = .85), day of the week (P = .099), month (P = .57), or season of the year (P = .47). Therefore, the findings from this prospective 35-month confirmation study did not support the common perception that physicians or nurses maybe either "black clouds" or "white clouds." It is important that this meaningful result be shared with apheresis practitioners given that the label of being a "black cloud" may have undesirable psychological implications to the physicians and nurses.

Management of chronic myeloid leukemia in the setting of pregnancy: when is leukocytapheresis appropriate? A case report and review of the literature.

BACKGROUND: Chronic myeloid leukemia (CML) is a common hematologic malignancy; however, its occurrence during pregnancy is unusual due to its low prevalence in females of childbearing age. There are conflicting reports of how to best manage CML in pregnancy, particularly in the setting of leukocytosis. HEMAPHERESIS: A 30-year-old female was diagnosed with CML at 18 weeks' estimated gestational age. On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 × 109 /L and platelet count of 366 × 109 /L. Her disease was managed during pregnancy using interferon-α alone despite persistent leukocytosis. CONCLUSION: CML may be effectively managed during pregnancy, even in the setting of leukocytosis, without the application of leukocytapheresis. Management relies not only upon the coordination of drug therapy and fetal monitoring, but requires close communication between multiple medical disciplines. Leukocytapheresis has been safely performed during pregnancy and may be a suitable adjunct management strategy in pregnant patients diagnosed with CML with specific clinical presentations, such as hyperleukocytosis (WBC count > 150 × 109 /L) and/or symptomatic leukostasis.

Survey on Transfusion-Transmitted Cytomegalovirus and Cytomegalovirus Disease Mitigation.

CONTEXT: - Cytomegalovirus (CMV) can be transmitted by cellular blood products, leading to severe disease in immunosuppressed patients such as neonates and transplant recipients. To mitigate transfusion-transmitted CMV (TT-CMV), "CMV-safe" blood products (leukoreduced and/or CMV-seronegative) are transfused. Attempts to develop practice guidelines for TT-CMV mitigation have been limited by paucity of high-quality clinical trials. OBJECTIVE: - To assess current TT-CMV mitigation strategies across medical institutions for specific at-risk populations. DESIGN: - Supplemental questions regarding TT-CMV and CMV disease mitigation were added to a College of American Pathologists Transfusion Medicine (Comprehensive) Participant Survey in 2015, addressing whether a given institution provided CMV-safe products for 6 at-risk patient populations. RESULTS: - Ninety percent (2712 of 3032) of institutions reported providing universally leukoreduced blood products. Among institutions without universal leukoreduction, 92% (295 of 320) provided leukoreduced products on the basis of clinical criteria. Eighty-three percent (2481 of 3004) of respondents reported having availability of CMV-seronegative products; however, wide variation in policies was reported governing CMV-seronegative product use. Among all respondents, less than 5% reported using CMV prophylaxis and monitoring in high-risk patient groups. Transplant centers reported higher rates of CMV prophylaxis (25% [97 of 394] solid organ) and monitoring (15% [59 of 394] solid organ) for CMV-negative transplant recipients. CONCLUSIONS: - Universal leukoreduction is the primary strategy for mitigating TT-CMV. While most institutions have both CMV-seronegative and leukoreduced blood products available, consensus is lacking on which patients should receive these products. High-quality studies are needed to determine if CMV-seronegative and leukoreduced blood products are needed in high-risk patient populations.

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis.

BACKGROUND: The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice. STUDY DESIGN AND METHODS: A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data. RESULTS: If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score. CONCLUSIONS: In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center.

Plasma Transfusion Demystified: A Review of the Key Factors Influencing the Response to Plasma Transfusion.

Many studies have suggested that inappropriate plasma usage is common. An important factor contributing to futile plasma administration in most patients is the nonlinear relationship between coagulation-factor levels and the volume of plasma transfused. In this review, a validated mathematical model and data from the literature will be used to illuminate 3 key properties of plasma transfusion. Those properties are as follows: the effect of plasma transfusion on international normalized ratio (INR) is transient; for the same volume of transfused plasma, a greater reduction in INR is observed at higher initial INRs; and the effect of plasma transfusion on INR correction (ie, the difference between initial and final INRs) diminishes as more plasma is transfused. Frequent misunderstanding of these properties may contribute to inappropriate plasma usage. Therefore, this review will assist physicians in navigating these common pitfalls. Stronger understanding of these principles may result in a reduction of inappropriate plasma transfusions, thus potentially enhancing patient safety and reducing healthcare costs.