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Research Interests: Education, Immunology, Public Health, Public sector, Medicine, and 15 moreCanada, Humans, Animals, Psychological Intervention, Red Cross, Blood Safety, Clinical Sciences, Questionnaires, Intensive Care Medicine, Risk Assessment, Pandemic, Blood collection, Blood component transfusion, Cardiovascular medicine and haematology, and Blood Donor
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Research Interests: Virology, Medicine, Humans, Babesia, United States, and 13 moreAnimals, Blood, Follow-up studies, Babesiosis, Blood Transfusion, Blood Donors, New England Journalof Medicine, Babesia Microti, Blood smear, real time polymerase chain reaction, Cricetinae, mass Screening, and Medical and Health Sciences
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BACKGROUNDBabesia microti, a red blood cell (RBC) parasite transmitted naturally to vertebrate hosts by ixodid ticks, is endemic to the northeastern and upper midwestern United States, with the geographic range of infected ticks... more
BACKGROUNDBabesia microti, a red blood cell (RBC) parasite transmitted naturally to vertebrate hosts by ixodid ticks, is endemic to the northeastern and upper midwestern United States, with the geographic range of infected ticks expanding. B. microti is a blood safety issue with >200 transfusion‐transmissions reported.METHODSThe American Red Cross's Hemovigilance program investigated hospital‐reported transfusion‐transmitted babesiosis (TTB) cases. Follow‐up samples from involved donors were tested for B. microti antibodies and parasite DNA, the latter by real‐time polymerase chain reaction (PCR). Test‐positive donors were permanently deferred from future donations.RESULTSB. microti‐positive donors were implicated in 77 of 143 suspect TTB cases investigated from 2010 through 2017. In four cases, two positive donors were identified for a total of 81 positive donors. In three cases, a RBC unit was split and components transfused multiple times to the same pediatric recipient. RBCs were the transmitting product in all cases. At follow‐up, all involved donors were antibody positive; 25 donors were also PCR positive. Positive donations were collected throughout the year, peaking in the summer. Most donors (78) were resident of, or traveled to (2), an endemic state. One donor resided in a non‐endemic state without relevant travel history. One fatality listed babesia as a contributing factor. No implicated donation was screened by an investigational protocol.CONCLUSIONSBabesiosis remains a blood safety issue. Prior to FDA‐licensed screening test availability and final FDA Guidance, blood collectors in endemic states investigationally tested none, a portion, or all collections. Future expanded testing will reduce the frequency of TTB cases.
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Research Interests: Library Science, Immunology, Terrorism, Medicine, Motivation, and 15 moreDisasters, Humans, Infection Control, Habits, New York City, Risk factors, Clinical Sciences, Adult, Aircraft, Biological markers, Risk Factors, Blood Donors, mass Screening, Cardiovascular medicine and haematology, and Blood Donor
Research Interests: Immunology, Virology, Medicine, Humans, Male, and 15 moreClinical Sciences, Aged, Antibody, West Nile Fever, Blood Transfusion, Meningoencephalitis, Aortic Valve, Transfusion, Aseptic meningitis, immunoglobulin G, Heart Diseases, Heart Valve Prosthesis Implantation, immunoglobulin M, Cardiovascular medicine and haematology, and Coronary Artery Bypass
BackgroundThe Transfusion‐Transmissible Infections Monitoring System (TTIMS) combines data from four US blood collection organizations including approximately 60% of all donations to monitor demographic and temporal trends in infectious... more
BackgroundThe Transfusion‐Transmissible Infections Monitoring System (TTIMS) combines data from four US blood collection organizations including approximately 60% of all donations to monitor demographic and temporal trends in infectious disease markers and policy impacts.Study Design and MethodsHuman immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) consensus‐positive definitions combined serology and nucleic acid testing results. These along with donor and donation characteristics were assembled into a single data set. Overall donation prevalence and demographic subsets were compared pre‐ and post‐implementation of the 2015 change in men who have sex with men (MSM) deferral policy, among other prevalence comparisons.ResultsFrom October 2015 to September 2019, there were 712 HIV‐, 1735 HBV‐, and 5217 HCV‐positive samples identified from approximately 27.5 million donations (>9.4 million donors). Prevalences per 100 000 donations were 2.6 (HIV), 6.3 (HBV), and 19.0 (HCV), and the highest for all three agents were in donations from first‐time male donors. Two slight but significant increases in HIV prevalence were observed, both for comparisons of Year 1 (pre‐MSM policy change) versus Year 4 (post‐MSM policy change) for first‐time males and first‐time females; in contrast, similar comparisons demonstrated decreases in HCV prevalence (all donors and general trends for males and females). Except for HIV, prevalence increased with age; for all agents, prevalence was markedly higher in the south.ConclusionsNo major trends were observed over 4 years covering the MSM policy change from indefinite to a 12‐month deferral, but ongoing monitoring is warranted. Demographic trends are consistent with those observed in other donor studies and community trends.
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ABSTRACT When xenotropic murine leukemia virus-related virus (XMRV) was first reported in association with chronic fatigue syndrome, it was suggested that it might offer a risk to blood safety. Thus, the prevalence of the virus among... more
ABSTRACT When xenotropic murine leukemia virus-related virus (XMRV) was first reported in association with chronic fatigue syndrome, it was suggested that it might offer a risk to blood safety. Thus, the prevalence of the virus among blood donors and, if present, its transmissibility by transfusion need to be defined. Two populations of routine blood donor samples (1435 and 13,399) were obtained for prevalence evaluations; samples from a linked donor-recipient repository were also evaluated. Samples were tested for the presence of antibodies to XMRV-related recombinant antigens and/or for XMRV RNA, using validated, high-throughput systems. The presence of antibodies to XMRV could not be confirmed among a total of 17,249 blood donors or recipients (0%; 95% confidence interval [CI], 0%-0.017%); 1763 tested samples were nonreactive for XMRV RNA (0%; 95% CI, 0%-0.17%). Evidence of infection was absent from 109 recipients and 830 evaluable blood samples tested after transfusion of a total of 3741 blood components. XMRV and related murine leukemia virus (MLV) markers are not present among a large population of blood donors and evidence of transfusion transmission could not be detected. Thus, these viruses do not currently pose a threat to blood recipient safety and further actions relating to XMRV and MLV are not justified.
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Research Interests: Epidemiology, Immunology, Medicine, Hepatitis C, Humans, and 13 moreUnited States, Female, Male, Hepatitis C Virus, Clinical Sciences, Sex Factors, Blood Transfusion, Blood Donors, Hepatitis B virus, Virus diseases, Transfusion, Cardiovascular medicine and haematology, and Epidemiological monitoring
BackgroundSensitive triplex nucleic acid tests (NATs) are implemented for blood donation screening worldwide. Assays have variable ability to detect low‐level hepatitis B virus (HBV) DNA. At borderline DNA detection levels, where Poisson... more
BackgroundSensitive triplex nucleic acid tests (NATs) are implemented for blood donation screening worldwide. Assays have variable ability to detect low‐level hepatitis B virus (HBV) DNA. At borderline DNA detection levels, where Poisson distribution impacts results, distinguishing true‐positive from false‐positive results is challenging. Algorithms are needed to confirm such low‐level HBV DNA–positive samples.Study Design and MethodsA total of 135 blood donor samples reactive by one or more HBV markers that provided discrepant results were tested undiluted with four commercial NATs: Ultrio, Ultrio Plus, MPX, and a quantitative assay (SuperQuant). To further explore discrepancies, three additional in‐house NATs including real‐time polymerase chain reaction (PCR) and nested PCR and sequencing were performed.ResultsThe numbers reactive of these 135 “difficult” samples by four commercial NATs were as follows: 39 of 107 (36%) with SuperQuant, 40 (30%) with Ultrio, 100 (74%) with Ultrio Plus, and 102 (76%) with MPX. Of the seven NATs, 109 (81%) samples were reactive by at least two assays and thus considered confirmed positive of which 67 (50%) generated a sequence. Ultrio Plus and MPX performed similarly as above (80%‐85% detected of 109 and 81%‐90% of 67, respectively). Older (median, 49 years), HBV core antibody–reactive donors carried predominantly Genotype A (58%) with high‐frequency amino acid substitutions in the major hydrophilic region of the S‐protein. Younger (median, 24 years) hepatitis B surface antigen–positive donors carried wild‐type strains predominantly Genotype B (32%) and E (24%), the latter in an apparent cluster.ConclusionsHighly sensitive NATs require new confirmatory algorithms as presented optimally using different genomic regions or sequence generation. The introduction of immigration‐related HBV genotypes may impact HBV epidemiology in the United States.
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BackgroundHepatitis B virus (HBV) DNA‐positive yield since nucleic acid testing (NAT) implementation (minipools of 16 [MP16]) was reported for the first year. We have updated those figures, evaluated the current value of all HBV tests,... more
BackgroundHepatitis B virus (HBV) DNA‐positive yield since nucleic acid testing (NAT) implementation (minipools of 16 [MP16]) was reported for the first year. We have updated those figures, evaluated the current value of all HBV tests, calculated the HBV residual risk before and after the introduction of MP‐NAT, and estimated residual risks with further improvements in HBV screening for US blood donations.Study Design and MethodsAll donations were screened by US‐required serologic HBV tests and for HBV DNA by MP‐NAT (Novartis/Gen‐Probe). Further testing by individual‐donation polymerase chain reaction (ID‐PCR) confirmed various classes of MP‐NAT–reactive or –nonreactive donations. The hepatitis B surface antigen (HBsAg)‐yield method was used to calculate incidence and the incidence–window‐period model used to define residual risk.ResultsOf approximately 12.8 million donations screened during 2009 to 2011, a total of 1368 HBV confirmed positives including 941 by MP‐NAT were observed (combined 4.32% positive predictive value) of which five were seronegative NAT‐yield donations (1:2.6 million) and 25 HBsAg‐yield (anti‐HBc–nonreactive) donations from which an incidence of 1.62/100,000 person‐years (vs. 3.43 during 2006‐2008) and residual risk of 1:592,000 to 1:754,000 were calculated. With the addition of MP‐NAT, and resulting 8.8‐day window‐period reduction, residual risks decreased to 1:765,000 to 1:1,006,000. Of the 1368 positives, 99.6% were detected by serology and 68.8% by MP‐NAT; ID‐PCR detected 427 more infected donors than MP‐NAT.ConclusionsHBV MP‐NAT and decreases in HBV incidence (likely vaccine‐related) in the United States have reduced residual risks to levels comparable to those of human immunodeficiency virus and hepatitis C virus and raise the question of the continued need for all three HBV markers for blood donation screening. Further reductions in residual risk will require the implementation of more sensitive HBV‐NAT methods including ID‐NAT.
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Research Interests: Immunology, Incidence Geometry, Medicine, Hepatitis B, Humans, and 15 moreFemale, Male, Incidence, Risk factors, Clinical Sciences, Risk Factor, Time Factors, Risk Factors, Blood Donors, Hepatitis B virus, HBsAg, Seroconversion, Residual risk, Cardiovascular medicine and haematology, and Blood Donor
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Background Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined (“hybrid immunity”), result in partial protection from subsequent... more
Background Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined (“hybrid immunity”), result in partial protection from subsequent infection and strong protection from severe disease. Proportions of the US population who have been infected, vaccinated, or have hybrid immunity remain unclear, posing a challenge for assessing effective pandemic mitigation strategies. Methods In this serial cross-sectional study, nationwide blood donor specimens collected during January–December 2021 were tested for anti-spike and anti-nucleocapsid antibodies, and donor COVID-19 vaccination history of ≥1 dose was collected. Monthly seroprevalence induced from SARS-CoV-2 infection, COVID-19 vaccination, or both, were estimated. Estimates were weighted to account for demographic differences from the general population and were compared temporally and by demographic factors. Results Overall, 1 123 855...
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ABSTRACTWest Nile virus (WNV) infection outcomes vary among individuals, with most infections resulting in asymptomatic or mild flu-like symptoms. We previously reported an association between early cytokine production and symptom outcome... more
ABSTRACTWest Nile virus (WNV) infection outcomes vary among individuals, with most infections resulting in asymptomatic or mild flu-like symptoms. We previously reported an association between early cytokine production and symptom outcome following WNV infection in US blood donors. In this meta-analysis, we found that WNV-infected females reported more symptoms than WNV-infected males, despite similar initial viremia and type I interferon responses. As the infection progressed, males exhibited a protracted cytokine response—marked by sustained CCL2 (MCP-1), CCL11 (eotaxin-1), CXCL10 (IP-10) and IL-15—that was absent in females. Our results suggest that sex differences may be a factor in sustaining WNV immunity.
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Abstract: West Nile virus (WNV) appeared in the U.S. in 1999 and has since become endemic, with yearly summer epidemics causing tens of thousands of cases of serious disease over the past 14 years. Analysis of WNV strains isolated during... more
Abstract: West Nile virus (WNV) appeared in the U.S. in 1999 and has since become endemic, with yearly summer epidemics causing tens of thousands of cases of serious disease over the past 14 years. Analysis of WNV strains isolated during the 2006–2007 epidemic seasons demonstrates that a new genetic variant had emerged coincidentally with an intense outbreak in Idaho during 2006. The isolates belonging to the new variant carry a 13 nt deletion, termed ID-Δ13, located at the variable region of the 3′UTR, and are genetically related. The analysis of deletions and insertions in the 3′UTR of two major lineages of WNV revealed the presence of conserved repeats and two indel motifs in the variable region of the 3′UTR. One human and two bird isolates from the Idaho 2006–2007 outbreaks were sequenced using Illumina technology and within-host variability was analyzed. Continued monitoring of new genetic variants is important for public health as
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Background Hepatitis C virus (HCV) infection rates among US blood donors have been well characterized; however, few studies evaluated HCV genotypes among blood donors. Monitoring trends in disease and demographic patterns contributes to... more
Background Hepatitis C virus (HCV) infection rates among US blood donors have been well characterized; however, few studies evaluated HCV genotypes among blood donors. Monitoring trends in disease and demographic patterns contributes to understanding the safety of the blood supply. We examined the demographic characteristics and distribution of HCV genotypes/subgenotypes for nearly a 16-year period among blood donors confirmed positive for HCV RNA but antibody negative (defined as nucleic acid testing [NAT] yield). Methods A retrospective assessment of demographic characteristics and testing data was used to determine temporal trends and geographical distribution of HCV genotypes/subgenotypes among American Red Cross blood donors confirmed positive as HCV-NAT yield. Results From 2003–2018, 343 donors (0.38/100 000 donations; 95% CI, .35–.43) were confirmed positive as HCV-NAT–yield cases. Temporal analysis revealed a significant increase in HCV-NAT–yield cases of 54.1% between 2009 ...
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ABSTRACTWe report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seropositivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors. We additionally... more
ABSTRACTWe report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seropositivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors. We additionally describe the longitudinal dynamics of immunoglobulin-G, immunoglobulin-M, and in vitro neutralizing antibody titers in COVID-19 patients. Neutralizing antibodies rise in tandem with immunoglobulin levels following symptom onset, exhibiting median time to seroconversion within one day of each other, and there is >93% positive percent agreement between detection of immunoglobulin-G and neutralizing titers.
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Trypanosoma cruzi is endemic to the Americas where it demonstrates multiple lineages over a vast geographic range (i.e., United States to Argentina). These lineages possess divergent geographic and biologic characteristics, including... more
Trypanosoma cruzi is endemic to the Americas where it demonstrates multiple lineages over a vast geographic range (i.e., United States to Argentina). These lineages possess divergent geographic and biologic characteristics, including variations in disease manifestations. Herein, we report the frequency of parasitemia among seropositive US blood donors and the potential association between parasite lineage and transfusion transmission. Blood donors identified as T. cruzi seropositive during screening were enrolled in follow-up studies, including hemoculture testing and a risk factor questionnaire. Positive hemocultures were expanded to obtain sufficient parasites for molecular lineage determination and analysis. Country of birth, obtained from the questionnaire, was used to predict parasite lineage in the absence of demonstrable parasitemia for infected donors. Eighteen (6.8%) of 263 seropositive donors were hemoculture positive. Among the 17 hemocultures expanded for lineage determi...
Research Interests: Immunology, Biology, Medicine, Humans, Female, and 15 moreMale, Polymerase Chain Reaction, Young Adult, Risk factors, Clinical Sciences, Aged, Middle Aged, Trypanosoma Cruzi, Adult, Risk Factors, Blood Donors, Transfusion, Surveys and Questionnaires, Transfusion reaction, and Cardiovascular medicine and haematology
Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of... more
Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV- and WNV-infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through immunoglobulin G engagement of Fcγ receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity-including fever, viremia, and viral loads in spinal cord and testes-and increased mortality. Antibody-dependent enhancement may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.
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or antibody-positive (titer 256) units caused symptomatic infections in 34% of subjects. However, they are not supported by human data. Of 29 known PCR-positive units that were transfused, only one recipient (3.4%) became symptomatically... more
or antibody-positive (titer 256) units caused symptomatic infections in 34% of subjects. However, they are not supported by human data. Of 29 known PCR-positive units that were transfused, only one recipient (3.4%) became symptomatically ill, and there were no reported symptomatic cases from those receiving the 29 PCR-negative units. Using the transmissibility and progression estimates from Bish and coworkers, we would suppose that in 29 known PCR-positive units transfused, five to six recipients would develop uncomplicated yet symptomatic infections, while three to four would have complicated babesiosis with a mortality of 12%. Thus, Bish and colleagues have likely overstated the burden of TTB morbidity and mortality. In summary, while decision analysis and cost-effectiveness modeling are well suited to inform policy on this topic, the most recent analysis likely overestimates the burden of transfusion-transmitted babesiosis and the cost-effectiveness of blood screening in endemic areas. Policy-makers would be well served to closely inspect all available models and each of their strengths and limitations before promulgating guidance.
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Babesia microti causes transfusion-transmitted babesiosis (TTB); currently, blood donor screening assays are unlicensed but used investigationally. We developed a decision tree model assessing the comparative- and cost-effectiveness of B.... more
Babesia microti causes transfusion-transmitted babesiosis (TTB); currently, blood donor screening assays are unlicensed but used investigationally. We developed a decision tree model assessing the comparative- and cost-effectiveness of B. microti blood donation screening strategies in endemic areas compared to the status quo (question regarding a history of babesiosis), including testing by: 1) universal antibody (Ab), 2) universal polymerase chain reaction (PCR), 3) universal Ab/PCR, and 4) recipient risk-targeted Ab/PCR. The model predicted the number of TTB cases, complicated TTB cases, cases averted, and quality-adjusted life years (QALYs). Economic outcomes included each strategy's per-donation cost, waste (number of infection-free units incorrectly discarded), and waste index (number wasted units/number true positives). Sensitivity analyses examined uncertainty in transmission probabilities, prevalence rates, and other key model inputs. Universal PCR in four endemic states would prevent 24 to 31 TTB cases/100,000 units transfused (pht) at an incremental cost-effectiveness ratio (ICER) of $26,000 to $44,000/QALY (transmission probability dependent) and waste index of zero. Universal Ab/PCR would prevent 33 to 42 TTB cases pht at an ICER of $54,000 to $83,000/QALY and waste index of 0.05. The questionnaire is most wasteful (99.62 units wasted pht; 208.62 waste index), followed by the risk-targeted strategy (76.27 units wasted pht; 0.68 waste index). The model predicted zero cases of TTB or complicated TTB with universal Ab/PCR (versus [33, 42] and [13, 18] pht, respectively [no screening]). Results are highly sensitive to transmission probabilities. Universal PCR in endemic states is an effective blood donation screening strategy at a threshold of $50,000/QALY. Using a higher cost-effectiveness ratio, universal Ab/PCR is the most effective strategy.
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ABSTRACT Background and Objectives Babesia microti, an intraerythrocytic parasite, causes babesiosis; transfusion-transmitted babesiosis (TTB) is reported primarily in the United States where no licensed screening tests are... more
ABSTRACT Background and Objectives Babesia microti, an intraerythrocytic parasite, causes babesiosis; transfusion-transmitted babesiosis (TTB) is reported primarily in the United States where no licensed screening tests are available.Materials and Methods Babesia microti donor screening results using investigational antibody and DNA tests in six US states are reviewed from both repository testing and prospective screening. Testing results performed in endemic counties from June 2012 to April 2014 were combined to update prevalence and marker duration in infected donors and estimate testing efficacy (i.e. the reduction of reported TTB cases).ResultsA total of 84 209 donations were tested and 331 were reactive by either antibody and/or DNA for a total prevalence of 0·39%. Of those that were DNA positive, the retrieved red cell units from nearly one-third caused infection in hamsters. In addition, eight units were identified that were PCR positive but antibody negative (window-period donors).Conclusions Screening is feasible, removing likely infectious donations. Followed donors retained PCR positivity over several months but antibody reactivity for over 3 years.
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Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile illness caused by the bacterium Anaplasma phagocytophilum. Although usually transmitted via tick bite, HGA may rarely also be acquired through transfusion. HGA during... more
Human granulocytic anaplasmosis (HGA) is an acute nonspecific febrile illness caused by the bacterium Anaplasma phagocytophilum. Although usually transmitted via tick bite, HGA may rarely also be acquired through transfusion. HGA during pregnancy may pose significant gestational risks due to altered maternal immune status and the potential for perinatal transmission. A pregnant 34-year-old Massachusetts woman with β-thalassemia trait was diagnosed at 32 weeks of gestation with transfusion-associated HGA (TAHGA) after receiving nine leukoreduced red blood cell transfusions. She was successfully treated with rifampin therapy and gave birth to a healthy child who tested negative for HGA after delivery. An implicated blood donor was subsequently identified through physician collaboration with the regional American Red Cross and Massachusetts Department of Public Health. This is the 11th reported case of HGA in pregnancy and is at least the sixth known case in which leukoreduction did no...