Prevalence of SARS-CoV-2 Viremia in Presymptomatic Blood Donors in the Delta and Omicron Variant Eras.

Presymptomatic plasma samples from 1596 donors reporting coronavirus disease 2019 infection or symptoms after blood donation were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and anti-S and anti-N antibodies. Prior infection and vaccination both protected from developing SARS-CoV-2 RNAemia and from symptomatic infection. RNAemia rates did not differ in the Delta and Omicron variant eras.

Frequent detection but lack of infectivity of SARS-CoV-2 RNA in presymptomatic, infected blood donor plasma.

Respiratory viruses such as influenza do not typically cause viremia; however, SARS-CoV-2 has been detected in the blood of COVID-19 patients with mild and severe symptoms. Detection of SARS-CoV-2 in blood raises questions about its role in pathogenesis as well as transfusion safety concerns. Blood donor reports of symptoms or a diagnosis of COVID-19 after donation (post-donation information, PDI) preceded or coincided with increased general population COVID-19 mortality. Plasma samples from 2,250 blood donors who reported possible COVID-19-related PDI were tested for the presence of SARS-CoV-2 RNA. Detection of RNAemia peaked at 9%-15% of PDI donors in late 2020 to early 2021 and fell to approximately 4% after implementation of widespread vaccination in the population. RNAemic donors were 1.2- to 1.4-fold more likely to report cough or shortness of breath and 1.8-fold more likely to report change in taste or smell compared with infected donors without detectable RNAemia. No infectious virus was detected in plasma from RNAemic donors; inoculation of permissive cell lines produced less than 0.7-7 plaque-forming units (PFU)/mL and in susceptible mice less than 100 PFU/mL in RNA-positive plasma based on limits of detection in these models. These findings suggest that blood transfusions are highly unlikely to transmit SARS-CoV-2 infection.

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.

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.

Acute Hemolytic Transfusion Reaction due to Anti-P1: A Case Report and Review of Institutional Experience.

BACKGROUND: Here we report a case of acute hemolytic transfusion reaction (HTR) due to anti-P1 and review our institutional database for prevalence of anti-P1 antibodies and frequency of anti-P1-mediated HTR. Anti-P1 antibodies, reported to be present in up to two-thirds of P2 individuals, are usually clinically insignificant. However, rare cases of acute HTR due to anti-P1 are reported. Case Report: We report the clinical and laboratory features of a mild acute HTR due to an IgM anti-P1 not detected by a routinely used antibody screening method. We reviewed our institutional database to investigate prevalence of anti-P1 antibodies identified in our patient population and frequency of HTR in patients with anti-P1. RESULTS: Analysis of RBC transfusion recipient data over the 10-year period from 2006 to 2015 showed prevalence of anti-P1 identified in our laboratory of 174 per 100,000 individuals. Frequency of HTR in patients with anti-P1 identified in our laboratory over a 10-year period was 1 in 1,429 RBC transfusions (0.07%). Conclusion: Our reported case of HTR mediated by IgM anti-P1 reactive at 37 °C confirms the potential of antibody screening methods designed to detect IgG antibodies to miss rare clinically significant IgM antibodies.

Drug-induced immune hemolytic anemia associated with anti-carboplatin and the first example of anti-paclitaxel.

BACKGROUND: Combined chemotherapy with carboplatin and paclitaxel is first-line treatment for lung and ovarian cancer. Drug-induced antibodies to carboplatin are rare but can cause severe, even fatal, hemolysis. Paclitaxel-induced immune hemolysis has not been reported. We describe a case of immune-mediated hemolysis associated with antibodies to carboplatin and paclitaxel in a woman with ovarian cancer who had received multiple chemotherapeutic agents over 7 years, including several courses of these two drugs. She required many transfusions. During a chemotherapy infusion the patient became hypotensive, was pale, and had rigors and red urine. The nadir hematocrit was 12.4%; peak bilirubin and lactate dehydrogenase were 16.3 mg/dL and 1188 units/L, respectively. STUDY DESIGN AND METHODS: Blood samples collected within hours after chemotherapy and 2 days later were tested for antibodies to carboplatin and paclitaxel. RESULTS: The direct antiglobulin test was positive with anti-IgG (3+) and anti-C3 (2+). The plasma collected shortly after chemotherapy agglutinated carboplatin-treated red blood cells (RBCs); untreated and paclitaxel-treated RBCs both reacted at the antiglobulin test most likely due to circulating carboplatin, paclitaxel, or both drugs. Serum collected 2 days later agglutinated (titer 2) and sensitized (titer 128) carboplatin-treated RBCs; untreated and paclitaxel-treated RBCs were nonreactive. An acid eluate reacted weakly in the presence of polyethylene glycol with carboplatin-treated RBCs. The serum reacted with untreated and enzyme-treated RBCs in the presence of soluble carboplatin and paclitaxel. CONCLUSION: Anti-carboplatin and the first example of anti-paclitaxel were detected in this patient's sample.

Transfusion-associated graft-versus-host disease in a liver transplant recipient: an unusual presentation and review of the literature.

BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, nearly universally fatal complication from transfusion of nonirradiated cellular blood components, occurring when a recipient's immune system is unable to recognize and destroy transfused T lymphocytes. Irradiation of cellular components eliminates this risk. We present an unusual case of a liver transplant recipient developing TA-GVHD 13 weeks after transfusion of a random unit of nonirradiated red blood cells (RBCs) that happened to be from a donor homozygous for an HLA haplotype shared by the patient. STUDY DESIGN AND METHODS: This study was a single case review of a liver transplant recipient who developed skin GVHD and marrow aplasia. Clinical course and the chimerism studies involving the patient, the liver donor, and the blood donor are detailed. RESULTS: The patient presented 3 months posttransplant with GVHD of his skin and marrow aplasia. In addition to standard antigraft immunosuppression, this patient had started the interleukin-1 receptor antagonist anakinra on Posttransplant Day 13 for an acute gout flare. Chimerism studies on the patient's peripheral blood identified a population of CD3 cells that did not originate with either the patient or his liver donor. HLA studies and microsatellite profiling of the unknown CD3 population identified the source of the patient's TA-GVHD, a unit of nonirradiated, nonleukoreduced apheresis RBCs. CONCLUSION: Use of an immunomodulating agent may have contributed to the development of TA-GVHD in a liver transplant patient who received a random unit of nonirradiated RBCs by chance from an unrelated haploidentical donor.

The immunohematologic and patient safety benefits of a centralized transfusion database.

BACKGROUND: The transfusion medical record is an important tool for providing safe and appropriate blood. However, many patients seek care at more than one hospital and this record is usually not portable. We posited that a centralized transfusion service database (CTS-D) offers benefits through tracking blood types, transfusion requirements, and detecting wrong blood in tube (WBIT). STUDY DESIGN AND METHODS: Records held in the CTS-D from 1997 to 2010 were queried to enumerate those seen at more than one hospital versus one hospital only. Transfusion-related attributes were collected including red blood cell (RBC) antibodies, transfusion requirements, and reactions. WBITs detected due to historical ABO typing were tallied. A review of blood orders that required alteration based on requirements held in the CTS-D was completed. RESULTS: There were 724,584 records; 10.9% of patients had been tested or received blood transfusion at more than one hospital. Of the 63,973 records with RBC alloantibodies, a greater proportion of patients were seen at more than one hospital versus one hospital only (7.11% vs. 3.97%, p < 0.005). Of the 97,687 patient records that required special processing, patients seen at one hospital had a lower rate than those at more than one hospital (12.13% vs. 24.59%, p < 0.005). There were 77 WBITs (0.18 WBITs per 1000 patients). An in-depth review of WBITs found an additional 26.3% (5 of 19) were detected because the current and historical ABO types were from two different hospitals within the CTS. CONCLUSIONS: The CTS-D provides a universal transfusion record that improves patient safety. As health care systems are enlarged, centralization of the transfusion component of the medical record should be considered.

Evolution in a centralized transfusion service.

The metropolitan Seattle area has utilized a centralized transfusion service model throughout the modern era of blood banking. This approach has used four laboratories to serve over 20 hospitals and clinics, providing greater capabilities for all at a lower consumption of resources than if each depended on its own laboratory and staff for these functions. In addition, this centralized model has facilitated wider use of the medical capabilities of the blood center's physicians, and a county-wide network of transfusion safety officers is now being developed to increase the impact of the blood center's transfusion expertise at the patient's bedside. Medical expectations and traffic have led the blood center to evolve the centralized model to include on-site laboratories at facilities with complex transfusion requirements (e.g., a children's hospital) and to implement in all the others a system of remote allocation. This new capability places a refrigerator stocked with uncrossmatched units in the hospital but retains control over the dispensing of these through the blood center's computer system; the correct unit can be electronically cross-matched and released on demand, obviating the need for transportation to the hospital and thus speeding transfusion. This centralized transfusion model has withstood the test of time and continues to evolve to meet new situations and ensure optimal patient care.

Pathology consultation on drug-induced hemolytic anemia.

Drug-induced immune hemolytic anemia is considered to be rare but is likely underrecognized. The consulting pathologist plays a critical role in integrating serologic findings with the clinical history, as drug-induced antibodies should be distinguished as either drug-dependent or drug-independent for appropriate clinical management. Drug-dependent antibodies (DDABs) are most commonly associated with cefotetan, ceftriaxone, and piperacillin, whereas fludarabine, methyldopa, ß-lactamase inhibitors, and platinum-based chemotherapeutics are frequent causes of drug-independent antibodies (DIABs). DDABs usually demonstrate a positive direct antiglobulin test and a negative elution, while DIABs are serologically indistinguishable from warm autoantibodies and are similarly steroid-responsive. Drug cessation is always recommended.

The association between the transfusion of older blood and outcomes after trauma.

Allogeneic packed red blood cells (PRBCs) suppress immunity and influence outcomes. The influence of blood on the risk of infection and death may be related to the duration of storage. We sought to determine whether blood storage duration was associated with infection or death in a large cohort of injury victims. We reviewed a cohort of trauma patients transfused at least 1 U of PRBCs within 24 h of admission to a level 1 trauma center. The outcomes of interest were complicated sepsis and mortality. We compared the amount of older blood (>14 days storage) given to patients who did or did not develop the outcomes of interest using univariate and multivariate methods. A total of 820 patients were included. Patients who died (n = 117) received more units of older blood than those who lived (5 U [inter quartile range {IQR}, 2-9] vs. 3 U [IQR, 2-6]; P < 0.001). Patients with complicated sepsis (n = 244) received a greater volume of older blood than those without complicated sepsis (6 U [IQR, 2-10] vs. 3 U [IQR, 1-5]; P < 0.001). After adjusting for clinical factors, including the total amount of blood transfused, patients receiving greater than or equal to 7 U of older blood had a higher risk of complicated sepsis than patients receiving 1 or fewer units (odds ratio, 1.9; P = 0.03). The risk for complicated sepsis and death in trauma victims who are transfused blood is high. The amount of older blood transfused is associated with complicated sepsis. Although the best strategy to minimize the effects of allogeneic blood is to avoid unnecessary transfusions, it may be particularly important to avoid transfusing multiple units of older blood.

The incidence of post-discharge surgical site infection in the injured patient.

BACKGROUND: Approximately 50% of surgical site infections (SSI) after elective surgery occur after discharge. Adequate surveillance for these infections requires a mechanism for post-discharge follow up. The incidence of SSI after injury is as high as 30%. As post-discharge follow up in the trauma population is difficult, we set out to ascertain the incidence of post-discharge SSI in a cohort of high-risk trauma patients. METHODS: Patients (n = 268) enrolled in a randomized controlled trial of leukoreduced versus regular blood transfusions were evaluated either in person or by structured telephone survey 28 days after admission regarding the presence of SSI. Inclusion criteria were age >17 years and blood transfusion within 24 hours of injury. RESULTS: Among the 268 patients, 39 (15%) developed a SSI. There were 27 SSI identified in hospital and 13 identified in the post-discharge period after a median length of stay of 17 days (one patient had more than one SSI). Although the 13 patients who developed a SSI in the post-discharge period comprised only 7% (13 of 194) of the cohort that had at least one operative procedure and survived to discharge, these patients represented 33% (13 of 39) of all patients who developed a SSI. CONCLUSION: Despite their prolonged length of stay compared with elective surgical patients, a significant proportion of SSI after injury occurs after discharge. These data support the need for a post-discharge surveillance system in either clinical trials or for quality assurance.

The beneficial effects of plasma exchange after severe burn injury.

Severe burn injury results in a systemic inflammatory response that leads to increased capillary permeability and fluid leak into the interstitium. This global systemic capillary leak can be attributed, at least in part, to inflammatory mediators produced as a result of cellular injury. Plasma exchange has been used in the management of a number of illnesses with a significant inflammatory component, and, therefore, may have a role in the early management of burn injury. The purpose of this study was to review our institutional experience using plasma exchange in the management of severe burn injury. We performed a retrospective review of all patients receiving plasma exchange at our burn center between 2001 and 2005. Data collected included the following: burn size, presence of inhalation injury, resuscitation fluid received, urine output, lactate levels, base deficit levels, and hematocrit before and after the exchange procedure. A total of 37 patients underwent plasma exchange during the 5-year study period and seven patients underwent two plasma exchange treatments. Average TBSA burned was 48.6% (range 18-82) and 73% of patients sustained an inhalation injury. After plasma exchange, hourly fluid volume received significantly decreased (P < .05) and base deficit, lactate, and hematocrit levels significantly improved. Plasma exchange in the early resuscitation period was associated with decreased fluid administration, as well as increased urine output in the period during and immediately after the procedure. These data suggest that plasma exchange may provide a useful tool in the management of severe burn injury.

Effects of leukoreduced blood on acute lung injury after trauma: a randomized controlled trial.

OBJECTIVE: The requirement for a blood transfusion after trauma is associated with an increased risk of acute lung injury. Residual leukocytes contaminating red cells are potential mediators of this syndrome. The goal of this trial was to test our hypothesis that prestorage leukoreduction of blood would reduce rates of posttraumatic lung injury. DESIGN: Double blind, randomized, controlled clinical trial. SETTING: University-affiliated level I trauma center in King County, Seattle, WA. PATIENTS: Two hundred sixty-eight injured patients requiring red blood cell transfusion within 24 hrs of injury. INTERVENTIONS: Prestorage leukoreduced vs. standard allogeneic blood transfusions. MEASUREMENTS AND MAIN RESULTS: We compared the incidence of acute lung injury and acute respiratory distress syndrome at early (< or = 72 hrs) and late (> 72 hrs) time points after injury. In a subset, we compared plasma levels of surfactant protein-D and von Willebrand factor antigen between intervention arms. Rates of acute lung injury (relative risk [RR] 1.06, 95% confidence interval [CI] .69-1.640) and acute respiratory distress syndrome (RR .96, 95% CI 0.48-1.91) were not statistically different between intervention arms early after injury. Similarly, no statistically significant effect of leukoreduced transfusion on rates of acute lung injury (RR .88, 95% CI .54-1.44) or acute respiratory distress syndrome (RR .95, 95% CI .58-1.57) was observed to occur late after injury. There was no significant difference in the number of ventilator-free days or in other ventilator parameters between intervention arms. No statistically significant effect of leukoreduced blood on plasma levels of surfactant protein-D or von Willebrand factor antigen was identified. CONCLUSIONS: Prestorage leukoreduction had no effect on the incidence or timing of lung injury or on plasma measures of systemic alveolar and endothelial inflammation in a population of trauma patients requiring transfusion. The relationship between transfusion and lung injury is not obviously explained by mechanistic pathways involving the presence of transfused leukocytes.

Leukoreduction of blood transfusions does not diminish transfusion-associated microchimerism in trauma patients.

BACKGROUND: Transfusion of trauma patients can result in long-term survival of donor white blood cells (WBCs) or "transfusion-associated microchimerism" (TA-MC). The aim was to determine whether leukoreduction of blood transfusions, advocated to reduce the immunomodulatory effect of transfusion, decreases the likelihood of developing TA-MC. STUDY DESIGN AND METHODS: A subgroup of trauma patients from a randomized trial was examined, evaluating the risk of infection following leukoreduced versus nonleukoreduced blood transfusion. Patients' blood was sampled at least 1 month after hospital discharge, and TA-MC was assessed with quantitative allele-specific polymerase chain reaction detection of differences at the HLA-DR locus or a panel of insertion-deletion polymorphism loci distributed throughout the chromosomal complement. At the time of blood sampling, a scripted interview was used to ascertain symptoms suggestive of chronic graft-versus host disease (cGVHD). RESULTS: For 67 patients evaluated, the mean age was 43 +/- 17 years and mean Injury Severity Score was 24 +/- 12. Median time from injury to blood sampling for TA-MC was 240 (interquartile range, 116-360) days. Nine of 32 patients (28%) in the nonleukoreduced transfusion group developed TA-MC compared to 13 of 35 patients (37%) in the leukoreduced group (p = 0.43). Subjects with TA-MC were no more likely than subjects without TA-MC to have at least one symptom suggestive of cGVHD (64% vs. 76%, respectively). CONCLUSIONS: TA-MC seems to be a prevalent condition among injured patients at the second of two regional trauma centers evaluated, suggesting that it is a common phenomenon after transfusion in the setting of injury. Although leukoreduction removes greater than 99.9 percent of donor WBCs, it fails to prevent or even substantially reduce the likelihood of developing TA-MC. TA-MC does not appear to be strongly associated with symptoms suggestive of cGVHD several months after transfusion.

The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial.

Allogeneic blood transfusions in surgical patients have been associated with an increased risk of infectious complications and organ dysfunction. Residual leukocytes contaminating units of packed red blood cells have been incriminated through the induction of anergy and/or a potentiated inflammatory response, leading to the possibility that leukoreduced red blood cell transfusion might mitigate these effects. We set out to evaluate the effect of leukoreduced red cell transfusion on the risk of infections complications in patients requiring transfusion following injury. We conducted a single-center, double-blinded randomized controlled trial of leukoreduced versus standard, nonleukoreduced red blood cell transfusions in injured patients receiving transfusion within 24 hrs of injury. The primary endpoint was infectious complications within 28 days of randomization. Secondary end points were multiple organ failure, length of stay, febrile episodes, and mortality. Two hundred sixty eight subjects were eligible for analysis. Rates of infectious complications were similar in subjects receiving leukoreduced transfusions (30%) or standard transfusions (36%) ([RR], 0.84 [0.55-1.3]) and there was no statistically significant effect of leukoreduced blood transfusion on mortality [RR, 1.20 (0.74-1.9)], febrile episodes [RR, 1.01 (0.89-1.2)], or organ dysfunction scores (5.9 vs. 6.6; P=0.29). Thus, pre-storage leukoreduction of allogeneic red blood cells had a small, but non-significant effect on the rate of infectious complication in this high-risk population requiring transfusion. There was no effect on the rates of febrile episodes, mortality, length of stay, or severity of organ dysfunction.