Prepare to adapt: blood supply and transfusion support during the first 2 weeks of the 2019 novel coronavirus (COVID-19) pandemic affecting Washington State.

BACKGROUND: The first coronavirus (COVID-19) case was reported in United States in the state of Washington, approximately 3 months after the outbreak in Wuhan, China. Three weeks later, the US federal government declared the pandemic a national emergency. The number of confirmed COVID-19 positive cases increased rather rapidly and changed routine daily activities of the community. STUDY DESIGN AND METHODS: This brief report describes the response from the hospital, the regional blood center, and the hospital-based transfusion services to the events that took place in the community during the initial phases of the pandemic. RESULTS: In Washington State, the first week of March started with four confirmed cases and ended with 150; by the end of the second week of March there were more than 700 cases of confirmed COVID-19. During the first week, blood donations dropped significantly. Blood units provided from blood centers of nonaffected areas of the country helped keep inventory stable and allow for routine hospital operations. The hospital-based transfusion service began prospective triaging of blood orders to monitor and prioritize blood usage. In the second week, blood donations recovered, and the hospital postponed elective procedures to ensure staff and personal protective equipment were appropriate for the care of critical patients. CONCLUSION: As community activities are disrupted and hospital activities switch from routine operations to pandemic focused and urgent care oriented, the blood supply and usage requires a number of transformations.

Blood use and transfusion needs at a large health care system in Washington state during the SARS-CoV-2 pandemic.

BACKGROUND: This report evaluates hospital blood use trends during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and identifies factors associated with the need for transfusion and risk of death in patients with coronavirus 2019 (COVID-19). METHODS: Overall hospital blood use and medical records of adult patients with COVID-19 were extracted for two institutions. Multivariate logistic regression models were conducted to estimate associations between the outcomes transfusion and mortality and patient factors. RESULTS: Daily blood use decreased compared to pre-COVID-19 levels; the effect was more significant for platelets (29% and 34%) compared to red blood cells (25% and 20%) at the two institutions, respectively. Surgical and oncologic services had a decrease in average daily use of platelets of 52% and 30%, and red blood cells of 39% and 25%, respectively. A total of 128 patients with COVID-19 were hospitalized, and 13 (10%) received at least one transfusion due to anemia secondary to chronic illness (n = 7), recent surgery (n = 3), and extracorporeal membrane oxygenation (n = 3). Lower baseline platelet count and admission to the intensive care unit were associated with increased risk of transfusion. The blood group distribution in patients with COVID-19 was 37% group O, 40% group A, 18% group B, and 5% group AB. Non-type O was not associated with increased risk of mortality. CONCLUSION: The response to the SARS-CoV-2 pandemic included changes in routine hospital operations that allowed for the provision of a sufficient level of care for patients with and without COVID-19. Although blood type may play a role in COVID-19 susceptibility, it did not seem to be associated with patient mortality.

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.

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.

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.

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.

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.

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.

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.

An update on ABO incompatible hematopoietic progenitor cell transplantation.

Hematopoietic progenitor cell (HPC) transplantation has long been established as the optimal treatment for many hematologic malignancies. In the setting of allogenic HLA matched HPC transplantation, greater than 50% of unrelated donors and 30% of related donors demonstrate some degree of ABO incompatibility (ABOi), which is classified in one of three ways: major, minor, or bidirectional. Major ABOi refers to the presence of recipient isoagglutinins against the donor's A and/or B antigen. Minor ABOi occurs when the HPC product contains the isoagglutinins targeting the recipient's A and/or B antigen. Bidirectional refers to the presence of both major and minor ABOi. Major adverse events associated with ABOi HPC transplantation includes acute and delayed hemolysis, pure red cell aplasia, and delayed engraftment. ABOi HPC transplantation poses a unique challenge to the clinical transplantation unit, the HPC processing lab, and the transfusion medicine service. Therefore, it is essential that these services actively communicate with one another to ensure patient safety. This review will attempt to globally address the challenges related to ABOi HPC transplantation, with an increased focus on aspects related to the laboratory and transfusion medicine services.

Critical role for P-glycoprotein expression in hematopoietic cells in the FVB.Mdr1a(-/-) model of colitis.

OBJECTIVE: P-glycoprotein (P-gp), the functional product of the multidrug resistance gene (MDR), is a transmembrane protein that extrudes substrates from the intracellular environment. P-gp is expressed on the apical surface of epithelial cells and on cells from the hematopoietic lineage. Human MDR polymorphisms have been associated with the increased risk of inflammatory bowel disease, and FVB/N animals deficient in mdr1a expression develop spontaneous colitis. Previous studies using adult bone marrow chimeras indicated that colitis development in this animal model was contingent on P-gp deficiency in radiation-resistant epithelial cells; however, the use of adult animals may mask the role of hematopoietic immune cells in colitis initiation, due to preexisting epithelial abnormalities. SUBJECTS AND METHODS: To assess the importance of P-gp expression in intestinal epithelial and hematopoietic-derived cells on colitis induction in FVB.mdr1a(-/-) animals, we developed a neonatal model of bone marrow reconstitution. FVB/N and FVB.mdr1a(-/-) adult and neonatal animals were lethally irradiated and reconstituted with bone marrow from FVB/N or FVB.mdr1a(-/-) donors. Animals were observed for 20 weeks. RESULTS: Adult FVB/N animals deficient in P-gp expression in hematopoietically derived immune cells developed colitis similar to adult animals deficient in P-gp expression in radiation-resistant epithelial/stromal cells. Neonatal animals deficient in P-gp expression in hematopoietically derived immune cells developed a more histologically significant colitis than those deficient in P-gp expression in epithelial tissue. CONCLUSIONS: The use of a neonatal model of bone marrow reconstitution has revealed a critical role for P-gp expression in hematopoietically derived immune cells in colitis development in the FVB.mdr1a(-/-) model.

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.

Role of postnatal acquisition of the intestinal microbiome in the early development of immune function.

OBJECTIVES: Therapy with broad-spectrum antibiotics is a common practice for premature infants. This treatment can reduce the biodiversity of the fecal microbiota and may be a factor in the cause of necrotizing enterocolitis. In contrast, probiotic treatment of premature infants reduces the incidence of necrotizing enterocolitis. We hypothesized that 1 mechanism for these observations is the influence of bacteria on postnatal development of the mucosal immune system. MATERIALS AND METHODS: Expression of immune molecules and microbial sensors was investigated in the postnatal mouse gastrointestinal tract by real-time polymerase chain reaction. Subsequently, 2-week-old specific pathogen-free and microbial-reduced (MR; antibiotic treated) mice were compared for immune molecule and microbial sensor expression, mesenteric lymph node T-cell numbers and activation, intestinal barrier function/permeability, systemic lymphocyte numbers, and T-cell phenotype commitment. RESULTS: Toll-like receptor 2, 4, and 5 expression was highest in 2-week-old specific pathogen-free mice, and this expression was decreased in MR mice. There was no difference in intestinal tight-junctional function, as evaluated by fluorescein isothiocyanate-dextran uptake, but MR mice had increased bacterial translocation across the intestinal epithelial barrier. MR mice had significantly fewer splenic B cells and mesenteric lymph node CD4+ T cells, but there were normal numbers of splenic T cells. These systemic T cells from MR mice produced more interleukin-4 and less interferon-gamma and IL-17, indicative of maintenance of the fetal, T-helper cell type 2 phenotype. CONCLUSIONS: The present study shows that intestinal commensal microbiota have an influence on early postnatal immune development. Determining specific bacteria and/or bacterial ligands critical for this development could provide insight into the mechanisms by which broad-spectrum antibiotics and/or probiotic therapy influence the development of the mucosal immune system and mucosal-related diseases.

The ESCRT-III complex is required for nuclear pore complex sequestration and regulates gamete replicative lifespan in budding yeast meiosis.

Cellular aging occurs as a cell loses its ability to maintain homeostasis. Aging cells eliminate damaged cellular compartments and other senescence factors via self-renewal. The mechanism that regulates cellular rejuvenation remains to be further elucidated. Using budding yeast gametogenesis as a model, we show here that the endosomal sorting complex required for transport (ESCRT) III regulates nuclear envelope organization. During gametogenesis, the nuclear pore complex (NPC) and other senescence factors are sequestered away from the prospore nuclei. We show that the LEM-domain protein Heh1 (Src1) facilitates the nuclear recruitment of ESCRT-III, which is required for meiotic NPC sequestration and nuclear envelope remodeling. Furthermore, ESCRT-III-mediated nuclear reorganization appears to be critical for gamete rejuvenation, as hindering this process curtails either directly or indirectly the replicative lifespan in gametes. Our findings demonstrate the importance of ESCRT-III in nuclear envelope remodeling and its potential role in eliminating senescence factors during gametogenesis.