Apheresis practice variation during the COVID-19 pandemic: Results of a survey.

BACKGROUND: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. STUDY DESIGN AND METHODS: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. RESULTS: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. CONCLUSION: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.

Syndecan-1 Level, a Marker of Endothelial Glycocalyx Degradation, Is Associated With Fetal Exposure to Chorioamnionitis and Is a Potential Biomarker for Early-Onset Neonatal Sepsis.

The goal of this investigation was to identify the association between Syndecan-1 (S1) serum levels in preterm newborns exposed to chorioamnionitis (CA) in utero and the potential of S1 as a biomarker of early-onset neonatal sepsis. A cohort of preterm newborns born <33 weeks gestational age was recruited. Within 48 hours of birth, 0.5 mL of blood was drawn to obtain S1 levels, measured via ELISA. Placentas were examined and classified as having (1) no CA, (2) CA without umbilical cord involvement, or (3) CA with inflammation of the umbilical cord (funisitis). S1 levels were compared between preterm newborns without exposure to CA verus newborns with exposure to CA (including with and without funisitis). Preterm newborns exposed to CA were found to have significantly elevated S1 levels compared to those unexposed. Although S1 levels could not differentiate fetal exposure to CA from exposure to CA with funisitis, the combined CA groups had significantly higher S1 levels compared to those not exposed to CA. S1 level has the potential to become a clinically useful biomarker that could assist in the management of mothers and preterm newborns with CA and funisitis. Furthermore, S1 level could aid in the diagnosis and treatment of early-onset neonatal sepsis.

Defining the optimal calcium repletion dosing in patients requiring activation of massive transfusion protocol.

PURPOSE: Massive transfusion protocols (MTP) commonly result in severe hypocalcemia due to the calcium-binding affinity of citrate in blood components. The purpose of this study is to determine the optimal grams (g) of citrate to repletion calcium (Ca) milliequivalents (mEq) (Citrate:Ca) ratio to reduce 30-day mortality. METHODS: This was a retrospective, single-centered, cohort study at a level 1 trauma center evaluating trauma and surgical patients in need of MTP activation from January 1, 2010-July 31, 2021. Patients with severe hypocalcemia at baseline, defined as ionized calcium (iCa) <0.9 mmol/L, were compared to patients without severe hypocalcemia. The primary endpoint was to determine the optimal ratio of grams of citrate to calcium mEq to reduce mortality in patients receiving a MTP. Secondary endpoints included mortality at 24 h and 30 days, blood components used in MTP, and type of calcium used. RESULTS: Overall, 501 patients were screened for inclusion. Of these patients, 193 were excluded, leaving 308 patients, of which 165 patients (53.6%) had an iCa <0.9 mmol/L within 24 h and 143 patients (46.4%) had iCa ≥0.9 mmol/L within 24 h. The ratio of Citrate:Ca for each patient was not significantly associated with mortality at 24 h (P = 0.79) or 30 days (P = 0.91) at a repletion Citrate:Ca ratio of median 1.97 (IQR 1.14-2.91). The rate of mortality was lowest at a Citrate:Ca of 2 in both <24-h mortality and 30-day mortality. CONCLUSIONS: There were no differences in 24 h or 30 day mortality based on repletion ratios seen in this study. A Citrate:Ca ratio between 2 and 3 in patients undergoing MTP was sufficient to obtain a normalized iCa within 24 h of MTP activation regardless of baseline iCa level. Further prospective studies will be needed to determine the optimal Citrate:Ca ratio.

ABO blood group and procoagulant factors: the hypercoagulation hypothesis ABO and Procoagulant Factors.

BACKGROUND: The correlation between procoagulant levels-factor VIII (FVIII), von Willebrand factor (vWF), and fibrinogen-and risk of thrombosis has been well documented in adult populations. We hypothesize that interaction of passively transferred isoagglutinins in premature neonates with a compromised immune system may trigger an immune response that can target the immature gastrointestinal tract. The objective of this study is to evaluate if there are procoagulant level differences in preterm newborns stratified by ABO blood group. METHODS: VWF, FVIII, and fibrinogen levels were analyzed in neonates ≤32 weeks and/or birthweight ≤1500 g over the first 6 weeks of life. Demographic, blood type, and transfusion data were collected. RESULTS: Elevations in vWF and FVIII were found to be statistically significant in the third week of life in non-O neonates vs. type O neonates. FVIII was also found to be significantly elevated in week 1. Transfused neonates also showed elevations between weeks 0 and 3. CONCLUSION: There appears to be a time-dependent variation in procoagulant factor levels in preterm newborns. Although the clinical significance remains unclear, prothrombotic factors vWF and FVIII are significantly higher in non-O blood-type preterm neonates in the third week of life.

A Strategy for Wellness in a Pathology Residency Program: Enhancing Chances of Success During an Epidemic of Burnout.

Physician burnout is a national crisis with medicine among occupations with higher suicide risk, at 1.8 times the national average. Few pathology departments address this issue, and even fewer residency programs offer formal resiliency training. We implemented a high-stress environment resiliency strategy and an Accreditation Council for Graduate Medical Education-compliant curriculum to our residency program. Its purpose was to apply initiatives employed in the finance industry, then to measure their effectiveness. Utilizing methods from financial companies such as Goldman Sachs, we adopted the following initiatives in our residency program: (1) approach burnout as a dilemma requiring a tridimensional strategy: providing wellness training for the individual, programmatic group strategies, and an institutional wellness plan; (2) formalize a wellness curriculum, implementing wellness talks focused on stress prevention, management, and treatment; (3) offer free sessions with resilience coaches, psychological help, Employee Assistance Program, and chaplain services; (4) modify our mentorship program, pairing first-year residents with senior residents; (5) implement mindfulness practices; (6) provide easy access to volunteer opportunities and networking; (7) offer fitness center discounts. Effectiveness was measured through 2 surveys of 13 residents representing day 0 (before wellness initiatives were implemented) and at 1 year. Results indicate a significant improvement in utilization of wellness tools. This study demonstrates that wellness and resilience can be taught. Our ultimate goals are to increase wellness among pathology residents, to prepare them for a high-stress environment before entering the workforce, and to prepare them to incorporate the tools they have learned into their new workplaces.

Restoration of Normal Prothrombin Time/International Normalized Ratio With Fresh Frozen Plasma in Hypocoagulable Patients.

Fresh frozen plasma (FFP) is an effective reversal agent for hypocoagulable patients. Its proven efficacy continues to prompt its usage as both a prophylactic and a therapeutic therapy. Although published guidelines encouraging the appropriate administration of FFP exist, overutilization continues. The purpose of these ex vivo studies was to determine the effects of succeeding volumes of FFP supplementation on hypocoagulable plasma prothrombin time/international normalized ratio (PT/INR). By analyzing the decline in PT/INR with varying volumes of FFP, a minimal required volume of FFP could be identified representing the optimal volume to administer while still providing therapeutic effect. A total of 497 plasma samples were screened for elevated PT/INR values and 50 samples were selected for inclusion in this experiment. The initial PTs/INRs ranged from 12.5 to 43.4 seconds/1.42 to 4.91. Subsequent declines in PT/INR values were analyzed following addition of 50, 100, and 150 µL of FFP to a fixed volume of 250 µL of plasma (26.4 ± 5.318 seconds/2.99 ± 0.603, 13.3 ± 1.077 seconds/1.51 ± 0.122, 11.2 ± 0.712 seconds/1.27 ± 0.081, and 10.3 ± 0.533 seconds/1.16 ± 0.06, respectively). A nonlinear relationship between decline in INR values and percentage of FFP supplementation was demonstrated. The greatest effect on INR was obtained after supplementation with 50 µL (49%). Doubling and tripling the volume of FFP lead to significantly lower declines in INR (16% and 8%, respectively). Analysis of variance indicated a statistical significance with subsequent volume supplementation of FFP, but marginal clinical benefits exist between the PTs/INRs obtainable with increased FFP volume administration.

The relationship between reticulated platelets, intestinal alkaline phosphatase, and necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) affects up to 10% of extremely-low-birthweight infants, with a 30% mortality rate. Currently, no biomarker reliably facilitates early diagnosis. Since thrombocytopenia and bowel ischemia are consistent findings in advanced NEC, we prospectively investigated two potential biomarkers: reticulated platelets (RP) and intestinal alkaline phosphatase (iAP). METHODS: Infants born ≤ 32 weeks and/or ≤ 1500 g were prospectively enrolled from 2009 to 2012. Starting within 72 hours of birth, 5 weekly whole blood specimens were collected to measure RP and serum iAP. Additional specimens were obtained at NEC onset (Bell stage II or III) and 24 hours later. Dichotomous cut-points were calculated for both biomarkers. Non-parametric (Mann-Whitney) and Chi-square tests were used to test differences between groups. Differences in Kaplan-Meier curves were examined by log-rank test. The Cox proportional hazards model estimated hazard ratios. RESULTS: A total of 177 infants were enrolled in the study, 15 (8.5%) of which developed NEC (40% required surgery and 20% died). 14 (93%) NEC infants had "low" (≤ 2.3%) reticulated platelets, and 9 (60%) had "high" iAP (>0 U/L) in at least one sample before onset. Infants with "low" RP were significantly more likely to develop NEC [HR=11.0 (1.4-83); P=0.02]. Infants with "high" iAP were at increased risk for NEC, although not significant [HR=5.2 (0.7-42); P=0.12]. Median iAP levels were significantly higher at week 4 preceding the average time to NEC onset by one week (35.7 ± 17.3 days; P=0.02). CONCLUSION: Decreased RP serves as a sensitive marker for NEC onset, thereby enabling early preventative strategies. iAP overexpression may signal NEC development.

Use of therapeutic plasma exchange in the burn unit: a review of the literature.

Burn centers routinely treat a complex mix of patients with soft tissue injuries, including burn injuries, necrotizing soft tissue infections, and dermatologic conditions such as toxic epidermal necrolysis (TEN). In each of these conditions, fluid resuscitation, surgical interventions, and advances in critical care have improved survival significantly; however, there remains a subset of patients who do not respond to conventional means. It is because of these patients that we continue to seek means to "rescue" patients who are failing to respond to conventional care. Therapeutic plasma exchange (TPE) is an uncommon and underutilized treatment modality that has been used as a form of treatment "rescue." We provide a review of the literature describing the use of TPE in TEN, burn shock, and sepsis. Our review of the literature over the past 30 years demonstrates persistent clinical benefits and reduced morbidity and mortality with use of TPE in TEN, burn shock, and sepsis. Many studies demonstrate significant improvement in morbidity and mortality with TPE in patients suffering from these conditions. However, future well-designed studies of the role of TPE in conditions commonly encountered in burn units are indicated. Improved awareness of TPE may lead to increased use of this uncommonly utilized modality and allow for potential future collaboration in a prospective, randomized, controlled trial with a larger number of subjects.

Control of melanoma morphogenesis, endothelial survival, and perfusion by extracellular matrix.

The morphogenetic properties of endothelial cells and melanoma cells were tested under varying matrix quantities and distributions and under constant and saturating levels of growth factors. Aggressive melanoma cells self-assembled into cords vasculogenically only when seeded on thin matrices: nonaggressive melanoma cells did not mimic endothelial cell behavior under any matrix thickness. When buried in matrix, however, aggressive melanoma cells generated looping patterns that contained tumor cells and matrix. These patterns were different topologically and compositionally from cord-like structures or blood vessels but were nevertheless capable of conducting dye by microinjection or passive diffusion. When seeded on three-dimensional cultures of nonaggressive nonpattern-forming melanoma cells, prelabeled endothelial cells attached to, penetrated through, and survived for 2 weeks but failed to form vasculogenic cords. In cocultures containing aggressive melanoma cells, endothelial cells survived briefly but formed short cords only in contact with looping patterns formed by the aggressive tumor cells. Time-lapse recording showed that endothelial cells were lysed upon direct contact with aggressive melanoma cells. Looping patterns identified in human tissue samples were composed ultrastructurally of electron-dense material on either side of a layer of tumor cells; scattered red blood cells were seen in this central cellular layer. By immunohistochemistry, patterns labeled with laminin and fibrinogen colocalized to these looping laminin-positive patterns, suggesting the presence of plasma within these patterns from contiguous leaky tumor vessels. These observations are consistent with the perfusion of these patterns in vitro and with repeated demonstrations of the colocalization of intravenous tracers to looping laminin patterns in animal xenograft models by independent groups. Thus, the distribution and localized quantity of extracellular matrix in aggressive melanomas contributes to the regulation of tumor cell morphogenesis, modulates interactions between tumor cells and endothelial cells, and may contribute to an extravascular matrix-directed circulation.