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Objectives Monitoring is essential to safe anticoagulation prescribing and requires close collaboration among pathologists, clinicians, and pharmacists. Methods We describe our experience in the evolving strategy for laboratory testing of unfractionated heparin (UFH). Results An intrainstitutional investigation revealed significant discordance between activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) assays, prompting a transition from the former to the latter in 2013. With the increasing use of oral factor Xa inhibitors (eg, apixaban, rivaroxaban, edoxaban, betrixaban), which interfere with the anti-Xa assay, we adapted our protocol again to incorporate aPTT in patients admitted on oral Xa inhibitors who require transition to UFH. Conclusions Our experience demonstrates key challenges in anticoagulation and highlights the importance of clinical pathologists in helping health systems adapt to the changing anticoagulation landscape.

Introduction: The World Health Organization declared COVID-19 a global pandemic on 03/11/20. Subsequent concerns around caring for patients with sickle cell disease who require automated red blood cell (RBC) exchange transfusions emerged, especially in the setting of physical distancing and national shortages in blood product supplies. In this vulnerable population at high risk of allo-immunization, ideal transfusion parameters (e.g., antigen optimization) will likely grow increasingly difficult to satisfy and require careful evaluation and strategic planning. Methods: Automated RBC exchange transfusions were performed at the University of Alabama at Birmingham (UAB) in patients with sickle cell disease for a variety of clinical indications with the primary objective of lowering the amount of Hemoglobin S (goal 15%) and replacing it with Hemoglobin A. We collected the number of weekly RBC exchange transfusions performed and then compared the frequencies between 01/05/20 and 03/14/20 (pre-pandemic) to those between 03/15/20 and 08/01/20 (intra-pandemic) using a one-tailed t-test. We also examined the number of RBC units ordered per week at UAB, in both the inpatient and outpatient settings, shortly before and after the declaration of a global pandemic using a one-tailed t-test. Results: The mean frequency of RBC exchange transfusions performed per week was 8.1 [standard deviation 2.3] pre-pandemic and 8.6 [2.3] intra-pandemic (Figure 1a). There was no statistically significant difference (p=0.27) in the frequency between these two periods. Shortly prior to the start of the pandemic (02/23/20-03/14/20), a mean of 77.3 [17.9] units/week were ordered for outpatient RBC exchange transfusions. Shortly after the start of the pandemic (03/15/20-04/26/20), a mean of 55.3 [22.8] units/week were ordered for outpatient RBC exchange transfusions, which was also not significantly different (p=0.09). During this time period, the mean number of RBC units per week ordered in the inpatient surgical setting significantly declined from 719.3 [43.1] to 390.0 [46.8] as elective procedures were delayed (p Conclusions/Future Directions: The frequency of automated RBC exchange transfusions performed at UAB did not decrease after the onset of the pandemic. UAB was able to continue caring for patients with sickle cell disease receiving RBC exchange transfusions as the pandemic emerged and national blood product supplies declined despite a similar overall demand. Interestingly, there was also a concomitant decrease in the demand for RBCs from inpatient surgical settings as elective procedures were delayed, possibly contributing to the blood bank's ability to maintain ideal transfusion parameters and perform antigen optimization of transfused RBCs. As the COVID-19 pandemic continues, the national shortage of blood product supplies will likely worsen and necessitate multidisciplinary efforts, including intra-institutional and inter-institutional collaborations, to continue caring for patients with sickle cell disease receiving RBC exchange transfusions. Furthermore, community education, safely structured blood drives, and other efforts to encourage donations are essential to maintain the national blood product supply. Disclosures No relevant conflicts of interest to declare.

OBJECTIVES To compare the effects of two methods of formalin-fixed paraffin-embedded (FFPE) tissue harvesting on DNA quality and next-generation sequencing (NGS) quality metrics. METHODS DNA integrity number (DIN) and NGS quality metrics resulting from DNA extraction and sequencing of 199 sequential samples harvested via the Pinpoint Slide DNA Isolation System and the punch method were compared. RESULTS DNA extracted from FFPE tissue punches had higher DIN than that extracted from Pinpoint samples (mean ± SD, 6.18 ± 0.83 vs 5.09 ± 0.91; P < .0001), indicating less degradation. Lower DIN correlated with lower-quality metrics of NGS, that is lower percentage of unique on-target reads, average depth of coverage, and percentage of positions with coverage depth greater than or equal to 100×, 400×, and 1,000×. CONCLUSIONS Our study demonstrated methods to harvest tissue from FFPE blocks may affect quality of DNA, which in turn has an effect on other NGS quality metrics.

Informatics plays an important role in every aspect of the clinical pathology laboratory, blood bank, and transfusion medicine service. Part of this chapter focuses on regulatory standards including Current Procedural Terminology (CPT), International Classification of Diseases (ICD), Health Level Seven (HL7), and Logical Observation Identifier Names and Codes (LOINC). The remainder of the chapter focuses on relevant topics in informatics including: bar coding and tracking; laboratory information systems; laboratory automation; middleware; workflow optimization; and database schemas.

Acquired thrombotic thrombocytopenic purpura is primarily caused by the deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13. However, ADAMTS13 deficiency alone is often not sufficient to cause acute thrombotic thrombocytopenic purpura. Infections or systemic inflammation may precede acute bursts of the disease, but the underlying mechanisms are not fully understood. Herein, 52 patients with acquired autoimmune thrombotic thrombocytopenic purpura and 30 blood donor controls were recruited for the study. The plasma levels of human neutrophil peptides 1-3 and complement activation fragments (i.e. Bb, iC3b, C4d, and sC5b-9) were determined by enzyme-linked immunosorbent assays. Univariate analyses were performed to determine the correlation between each biomarker and clinical outcomes. We found that the plasma levels of human neutrophil peptides 1-3 and Bb in patients with acute thrombotic thrombocytopenic purpura were significantly higher than those in the control (P

Background: Acquired TTP is a potentially fatal syndrome, resulting from autoantibodies against ADAMTS13; however, ADAMTS13 deficiency or the presence of autoantibodies is not sufficient to cause disease or predict outcome. Infection or systemic inflammation often precedes the onset of acute TTP. We hypothesize that human neutrophil peptides (HNPs) 1-3, released from activated neutrophils or activation of complement, may be a trigger and a potential biomarker for acquired TTP; thus, we sought to determine the association between these biomarkers with in-hospital mortality during the acute setting. Methods: All patients admitted to our institution with the diagnosis of autoimmune TTP and ADAMTS13 level Results: Fifty one patients (28 females, 23 males; mean age: 43.8 years; 35 patients with initial TTP episode) were eligible and had frozen plasma for laboratory analysis. On admission, prior to the initiation of therapeutic plasma exchange, the mean hematocrit (Hct), platelet count (Plt), and lactate dehydrogenase (LDH) were 24.3%, 19,130/mL, and 1,132.5 IU/L, respectively. The mean plasma levels of HNPs1-3, Bb, iC3b, C4d, and sC5b-9 were 47.1 ng/mL, 15.8 mg/mL, 3.3 mg/mL, 3.1 mg/mL, and 1.7 mg/mL, respectively. Nine patients died during hospitalization. Univariate analysis demonstrated that the patients who died tended to be older (p=0.01) and had relapsed disease (p=0.02). Other clinical variables (gender, ethnicity, neurologic symptoms) and laboratory variables (Hct, Plt, absolute neutrophil count [ANC], creatinine [Cr], LDH, HNPs1-3, and complement markers) were not statistically different between survivors and non-survivors; however, age, Cr, and LDH had high effect sizes (Cohen'd=0.81, 1.13, and 0.82) while ANC and HNPs had moderate effect sizes (Cohen'd=0.48 and 0.56). These results indicate that the differences have practical significance and would have reached statistical significance if the sample sizes were increased. Decision tree analysis (see Figure 1) further showed that all 3 TTP patients that had Cr ≥3 mg/dL died. Moreover, none of the 30 TTP patients younger than 48.5 years old died. Interestingly, in the group older than or equal to 48.5 years, the mortality rate was higher if the patients had HNPs Conclusions: Mortality is increased in patients with acquired TTP if they are older (≥48.5 years), have worsened baseline renal function (Cr ≥3 mg/dL), or have baseline HNPs levels lower than 26.5 ng/dL or greater than or equal to 82.9 ng/dL. Complement activation markers and other baseline clinical and routine laboratory parameters were not different between survivors and non-survivors. Larger multicenter studies should be performed to confirm these findings, with attention to parameters with moderate to high effect sizes (i.e. age, Cr, LDH, ANC, and HNPs levels). Furthermore, basic science research is warranted to elucidate the role of HNPs in the pathogenesis of autoimmune TTP. Disclosures Zheng: Ablynx: Consultancy; Alexion: Research Funding.