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Background COVID‐19 convalescent plasma (CCP) is plasma collected from individuals who have recovered from SARS‐CoV‐2 infection. The FDA Emergency Use Authorization restricts use of CCP to high‐titer units only. The purpose of this study was to determine if donor ABO blood group was associated with SARS‐CoV‐2 antibody response, and subsequent qualification as high‐titer CCP. Methods All CCP donations collected from April 21, 2020 to September 1, 2020 were included. The Abbott ARCHITECT semi‐quantitative chemiluminescent microparticle immunoassay was used to assess IgG antibodies to the nucleocapsid protein of SARS‐CoV‐2. Units with a S/C value ≥4.5 were considered high titer. Results A total of 232 CCP donations were evaluated. There were no significant differences in the distribution of sex, age, and interval from symptom resolution to donation by ABO blood group. The mean SARS‐CoV‐2 IgG antibody S/C value was significantly lower in blood group O donations (3.6), compared to blood group A (5.0) donations (p

BACKGROUND Despite West Nile virus (WNV) blood donation screening using nucleic acid testing (NAT), donors with low viral loads not detected by mini-pool-NAT have led to transfusion transmitted (TT)-WNV infection. We describe a probable case of fatal TT-WNV infection from an individual donor (ID)-NAT non-reactive apheresis platelet donation. STUDY DESIGN AND METHODS An apheresis platelet donation was WNV ID-NAT reactive and prior donations from the same donor were investigated. A WNV ID-NAT non-reactive apheresis platelet unit collected 26 days earlier was transfused during heart transplantation to a patient who subsequently developed WNV neuroinvasive disease and expired. The source of the recipient's WNV infection was investigated. RESULTS Twenty-six days after collection of the suspect platelet unit, a donation from the same donor was WNV ID-NAT reactive and WNV IgM and IgG positive. In addition to the suspect platelet unit, the heart transplant recipient who developed WNV infection received 17 blood components from 24 donors. Serologic testing performed on 11 of the remaining 24 donors (46%) was WNV IgM negative. Pre-transplant recipient and heart donor samples tested WNV RNA and IgM negative. CONCLUSION A probable case of fatal neuroinvasive TT-WNV was linked to an infectious apheresis platelet unit undetected by WNV ID-NAT. It is hypothesized that the suspect unit was collected early in the viremic period when viral RNA was below the limit-of-detection of the ID-NAT assay. Implementation of ID-NAT screening of blood donors has not entirely eliminated the risk of TT-WNV infections, which may best be addressed by pathogen inactivation technologies.

Cold-stored low titer group O whole blood (LTOWB) is increasingly utilized in the initial resuscitation of exsanguinating trauma patients. We report on our early experience with LTOWB, focusing on logistics, implementation challenges, and outcomes.In February, 2019, LTOWB was incorporated into the massive transfusion protocol (MTP) activated for trauma patients in the emergency department (ED.) Up to 4 units of LTOWB were included in the MTP cooler, depending on availability, and were transfused prior to transfusion of any other blood products from the MTP cooler. Demographics, injury characteristics, and outcomes were obtained, and the logistics of LTOWB availability were reviewed.Over a 12-month period, MTP was activated for 74 trauma patients. Of those, 38 (51%) MTP included at least one unit of LTOWB, with 19/38 (50%) including 4 LTOWB units. A total of 177 units of LTOWB were purchased during the study period, and of those, 74 (42%) expired before use. Patients who received LTOWB had a similar mortality compared to those who received component therapy (39% vs. 47%; Odds Ratio [95% CI]: 0.7 [0.3, 2.0]; p = 0.72,) however, they were able to achieve a significantly higher plasma:pRBC ratio during the duration of MTP activation (mean [SD] 0.8 [0.2] vs. 0.4 [0.4]; mean difference [95% CI]: 0.4 [0.2, 0.5]; p 0.01.) CONCLUSIONS: Our early experience with LTOWB transfusion demonstrates feasibility, but also highlights challenges with inventory management. These findings triggered changes to our protocol aiming at minimizing wastage. The use of LTOWB may yield a higher plasma:pRBC ratio early during the resuscitation period. Further investigation is required to explore whether this may yield a survival advantage.III (Therapeutic/Care Management).

Background Mechanical circulatory support device (MCSD) patients with positive heparin-induced thrombocytopenia (HIT) screening pose a unique challenge, as clinicians must make rapid decisions about their anticoagulation and whether they can safely undergo cardiopulmonary bypass . We identified screening practices at our institution and other institutions nationwide that differed from American Society of Hematology (ASH) guidelines. This discovery prompted a data review to confirm the applicability of guidelines to this unique population and to highlight complications of "gestalt" screening. Methods Our study included MCSD patients with HIT testing from April 2014 to August 2020. We evaluated 510 PF4 IgG ELISA results. Results HIT was confirmed in 4.2% of patients. There was an increased prevalence of HIT in patients with nondurable (5.3%) vs durable devices (2.9%) or those in the preimplantation setting (1.3%), however this difference was not statistically significant (p = 0.26). None of the patients with a low probability 4T Score had HIT. All patients with a high probability 4T Score and PF4 immunoassay OD >2.0 had HIT. False positive results occurred in 22% of assays ordered for patients with a low probability 4T Score. Twelve patients with a low probability 4T Score and a false positive immunoassay were switched to a direct thrombin inhibitor (DTI) while awaiting confirmatory results. Two patients experienced clinically significant bleeding after conversion to a DTI. An organ was refused in one patient with false positive HIT screening. Conclusions Our findings demonstrate that an opportunity exists to improve clinical outcomes by re-emphasizing the utility of established guidelines and highlighting their safe use in the MCSD patient population.

BACKGROUND The microparticle content (MP%) of apheresis platelets-a marker of platelet activation-is influenced by donor factors and by external stressors during collection and storage. This study assessed the impact of apheresis technology and other factors on the activation status (MP%) of single-donor apheresis platelets. STUDY DESIGN AND METHODS Data from six US hospitals that screened platelets by measuring MP% through dynamic light scattering (ThromboLUX) were retrospectively analyzed. Relative risks (RRs) were derived from univariate and multivariable regression models, with activation rate (MP% ≥15% for plasma-stored platelets; ≥10% for platelet additive solution [PAS]-stored platelets) and MP% as outcomes. Apheresis platform (Trima Accel vs Amicus), storage medium (plasma vs PAS), pathogen reduction, storage time, and testing location were used as predictors. RESULTS Data were obtained from 7511 platelet units collected using Trima (from 16 suppliers, all stored in plasma, 20.0% were pathogen-reduced) and 2456 collected using Amicus (from four different collection facilities of one supplier, 65.0% plasma-stored, 35.0% PAS-stored, none pathogen-reduced). Overall, 30.0% of Trima platelets were activated compared to 45.6% of Amicus platelets (P

Development of antibody protection during SARS-CoV-2 (CoV-2) infection is a pressing question for public health and for vaccine development. We developed highly sensitive CoV-2-specific antibody and neutralization assays. CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n=87) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. CoV-2 neutralization was determined in COVID-19 and convalescent plasma up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which was also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Further, subjects who donated plasma further out from the diagnosis of COVID-19 appeared to have lower titers. Interestingly, some COVID-19 patients also contained NAbs against SARS Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

Purpose Unfractionated heparin exposure in patients undergoing mechanical circulatory support device (MCSD) implantation increases the risk for developing heparin-induced-thrombocytopenia (HIT). The false positive rate of HIT in this population using current standard testing is unknown. Postoperative and device related thrombocytopenia complicate the HIT diagnosis. Methods A retrospective analysis of patients undergoing MCSD pre-implantation assessment or implantation of MCSD (October 2014 - August 2020) was performed. The primary objective was to assess the incidence of HIT with positive PF4 IgG ELISA (PF4) and serotonin release (SRA) assays. False positive HIT was defined as PF4 ≥0.4 optical density (OD) and negative SRA. Argatroban usage was also assessed. Results 366 patients with 512 tests were analyzed. PF4 tests were performed in 128 patients (158 tests) undergoing pre-implantation assessment, 136 patients (185 tests) with non-durable devices (primarily Impella®), and 102 (169 tests) patients with durable devices (72 ventricular assist devices, 30 total artificial hearts). 25% (92/366) of patients had positive PF4 ≥0.4 OD and had subsequent SRA performed (92 patients, 122 tests). True positive HIT was documented in 13% (12/92) of PF4 positive patients consisting of 1 pre-implantation, 9 non-durable MCSD, and 2 durable MCSD patients. The mean PF4 for true positive HIT was 2.2±0.7 OD. False positive HIT was documented in 15% (19/128) of pre-implantation patients (mean PF4 0.9±0.6 OD), 14% (19/136) of non-durable MCSD patients (mean PF4 0.8±0.5 OD), and 41% (42/102) of durable MCSD patients (mean PF4 1.1±0.6 OD). Argatroban was administered in 40% (37/92) of patients with a positive PF4 and 67% (25/37) of patients with a negative SRA. Conclusion Without clinical suspicion of HIT, preoperative PF4 testing is not recommended. Patients with non-durable MCSD devices are at the highest risk of developing HIT (7%). Although a PF4 ≥0.4 OD is considered a positive screening test for HIT, a higher threshold should be considered for MCSD patients. To our knowledge, this is the first in depth assessment of the incidence of HIT in patients undergoing pre-implantation evaluation for both non-durable and durable MCS devices.

BACKGROUND ORTHO VISION Analyzer (Vision), is an immunohematology instrument using ID-MT gel card technology with digital image processing. It has a continuous, random sample access with STAT priority processing. The efficiency and ease of operation of Vision was evaluated at 5 medical centers. METHODS De-identified patient samples were tested on the ORTHO ProVue Analyzer (ProVue) and repeated on the Vision mimicking the daily workload pattern. Turnaround times (TAT) were collected and compared. Operators rated key features of the analyzer on a scale of 1 to 5. RESULTS A total of 507 samples were tested on both instruments at the 5 trial sites. The mean TAT (SD) were 31.6 minutes (5.5) with Vision and 35.7 minutes (8.4) with ProVue, which renders a 12% reduction. Type and screens were performed on 381 samples; the mean TAT (SD) was 32.2 minutes (4.5) with Vision and 37.0 minutes (7.4) with ProVue. Antibody identification with eleven panel cells was performed on 134 samples on Vision; TAT (SD) was 43.2 minutes (8.3). The installation, training, configuration, maintenance and validation processes are all streamlined to provide a short implementation time. The average rating of main functions by the operators was 4.1 to 4.8. Opportunities for improvement, such as flexibility with editing QC results, maintenance schedule, and printing options were identified. The capabilities to perform serial dilutions, to accept pediatric tubes, and review results by e-Connectivity are enhancements over the ProVue. CONCLUSIONS Vision provides shorter TAT compared to ProVue. Every site described a positive experience using Vision.

Background Serologic RhD-negative blood donors are tested by a method known to detect weak D antigen expression. Serology does not detect all red blood cells with RhD expression and RHD genotyping has been used to identify variant RHD alleles, which may lead to some RhD expression. The aim of this study was to determine the frequency of RHD variant alleles in serologic RhD-negative blood donors at a hospital-based donor center in Los Angeles. Study design and methods RHD genotyping of serologic RhD-negative blood donors over a 20-month period was performed using the Immucor RHD BeadChip assay. DNA sequencing was performed when the RHD BeadChip assay failed to assign a genotype. For RHD variants known or suspected to result in RhD expression, recipients of previous blood donations were investigated for alloimmunization. Results RHD genotyping was performed in 1174 RhD-negative blood donors, and 1122 were genotyped for RHCE variants. Eleven donors (0.94%) harbored mutations predicted to yield RhD expression. The predicted phenotypes were, in decreasing frequency, DEL, partial, and weak D phenotypes. Anti-D was not detected in 16 patients who had received blood from these donors after an average follow up of 182 days. Conclusion Genotyping can be used to identify donors with the potential to sensitize RhD-negative recipients. In this limited study, 0.94% of serologic RhD-negative blood donors were found to have variant RHD alleles that might cause alloimmunization in RhD-negative recipients. To our knowledge, a study of this nature has not been reported in the United States.

The majority of transfusions are performed in settings that could be considered “routine.” However, many unusual circumstances may arise that call for “nonroutine” thinking and practice on the part of the Transfusion Medicine team. These special clinical scenarios include examples, such as urgent transfusions, massive transfusions, autoimmune hemolytic anemia, intrauterine transfusion, and sickle cell disease. The questions and cases in this chapter will discuss those issues and more, and will emphasize recognition and management of patients and problems that are out of the norm in transfusion medicine.

Epstein-Barr virus (EBV) is known to play a key role in the development of several lymphoproliferative disorders (LPD), ranging from indolent lesions to highly aggressive lymphomas. Here, we describe an incidentally detected unique case of a localized EBV-positive large B cell LPD within a popliteal artery aneurysmal hematoma of a 91-year-old male. Histopathologic examination of an expanding right thigh mass demonstrated organizing hematoma with microscopic clusters of atypical large lymphoid cells with a non-germinal center B cell immunophenotype, a high proliferation rate by Ki-67 staining, and strong positivity for EBV-encoded RNA (EBER) by in situ hybridization. An 18-month follow-up revealed no evidence of disease progression. The presence of cytologically malignant EBV-positive large B cells supports a LPD, with a differential diagnosis that includes a spectrum of EBV-associated lesions, including diffuse large B cell lymphoma (DLBCL) of the elderly, DLBCL associated with chronic inflammation, as well as a variety of recently described indolent EBV-associated large B cell proliferations occurring in cardiac fibrin thrombi, atrial myxomas, and other unusual sites. This case is the first report of an indolent fibrin-associated EBV-positive LPD occurring in an aneurysmal hematoma of the extremity. This lesion may represent the indolent end of the spectrum of EBV-associated large B cell proliferations, and recognition of such lesions may prevent unnecessary aggressive treatment.

Massive intravascular hemolysis may overwhelm hemoglobin (Hgb) clearance mechanisms leading to accumulation of excess plasma free-Hgb and subsequent acute kidney injury. We present the case of a 44-year-old male with cardiac failure necessitating placement of a subcutaneous left ventricular assist device. Following insertion, the patient developed mechanical hemolysis and an acute decline in renal function. Three therapeutic plasma exchange procedures were performed resulting in a dramatic decrease in plasma free-Hgb levels and stabilization of renal function. This demonstrates that therapeutic plasma exchange can be used to decrease plasma free-Hgb in cases of intravascular hemolysis, possibly protecting the patient from hemoglobinuric acute kidney injury.