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BackgroundCache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the fall of 2020, a patient developed encephalitis 6 weeks following kidney transplantation and receipt of multiple blood transfusions.MethodsAfter ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens using reverse-transcription polymerase chain reaction (RT-PCR), the plaque reduction neutralization test, cell culture, and whole-genome sequencing.ResultsCVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole-genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation.ConclusionsOur investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

* Context.--Substantial variability between different antibody titration methods has been identified since the development and introduction of the uniform procedure in 2008. Objective.--To determine whether more recent methods or techniques decrease interlaboratory and intralaboratory variation measured using proficiency testing. Design.--Proficiency test data for antibody titration between 2014 and 2018 were obtained from the College of American Pathologists. Interlaboratory and intralaboratory variations were compared by analyzing the distribution of titer results by method and phase, comparing the results against the supplier's quality control titer, and by evaluating the distribution of paired titer results when each laboratory received a sample with the same titer twice. Results.--A total of 1337 laboratories participated in the antibody titer proficiency test during the study period. Only 54.1 % (5874 of 10 852) of anti-D and 63.4% (3603 of 5680) of anti-A reported responses were within 1 titer of the supplier's intended result. Review of the agreement between laboratories of the same methodology found that 78.4% (3139 of 4004) for anti-A and 89.0% (9655 of 10 852) of laboratory responses for anti-D fell within 1 titer of the mode response. When provided with 2 consecutive samples of the same titer (anti-D titer: 16), 85% (367 of 434) of laboratories using the uniform procedure and 80% (458 of 576) using the other method reported a titer difference of 1 or less. Conclusions.--Despite advances, interlaboratory and intralaboratory variance for this assay remains high in comparison with the strong reliance on titer results in clinical practice. There needs to be a reevaluation of the role of this test in clinical decision-making. (Arch Pathol Lab Med. 2023;147:1351-1359; doi: 10.5858/arpa.2022-0248-CP), Antibody titration in transfusion medicine is a commonly used clinical assay to detect the strength of reactivity of red cell antibodies present in a patient's plasma. (1) There are a [...]

* Context.--Modern RHD genotyping can be used to determine when patients with serologic weak D phenotypes have RHD gene variants at risk for anti-D alloimmunization. However, serologic testing, RhD interpretations, and laboratory management of these patients are quite variable. Objective.--To obtain interlaboratory comparisons of serologic testing, RhD interpretations, Rh immune globulin (RhIG) management, fetomaternal hemorrhage testing, and RHD genotyping for weak D-reactive specimens. Design.--We devised an educational exercise in which 81 transfusion services supporting obstetrics performed tube-method RhD typing on 2 unknown red blood cell challenge specimens identified as (1) maternal and (2) newborn. Both specimens were from the same weak D-reactive donor. The exercise revealed how participants responded to these different clinical situations. Results.--Of reporting laboratories, 14% (11 of 80) obtained discrepant immediate-spin reactions on the 2 specimens. Nine different reporting terms were used to interpret weak D-reactive maternal RhD types to obstetricians. In laboratories obtaining negative maternal immediate-spin reactions, 28% (16 of 57) performed unwarranted antiglobulin testing, sometimes leading to recommendations against giving RhIG. To screen for excess fetomaternal hemorrhage after a weak D-reactive newborn, 47% (34 of 73) of reporting laboratories would have employed a contraindicated fetal rosette test, risking false-negative results and inadequate RhIG coverage. Sixty percent (44 of 73) of laboratories would obtain RHD genotyping in some or all cases. Conclusions.--For obstetric and neonatal patients with serologic weak D phenotypes, we found several critical problems in transfusion service laboratory practices. We provide recommendations for appropriate testing, consistent immunohematologic terminology, and RHD genotype-guided management of Rh immune globulin therapy and RBC transfusions., In the United States and Canada, 0.06% to 2.2% of patients have red blood cells (RBCs) that type weakly reactive for RhD, termed 'serologic weak D phenotype.' (1-6) In past [...]

* Context.--ABO mistransfusions are rare and potentially fatal events. Protocols are required by regulatory agencies to minimize this risk to patients, but how these are applied in the context of massive transfusion protocols (MTPs) is not specifically defined. Objective.--To evaluate the approaches used by transfusion services for switching from universally compatible to patient ABO type-specific blood components during massive hemorrhage. Design.--We added 1 supplemental multiple-choice question to address the study objective to the 2019 College of American Pathologists proficiency test J-survey (J-A 2019). We also reviewed the available literature regarding this topic. Results.--A total of 881 laboratories responded to the supplemental question. Approximately 80% (704 of 881) reported a policy for ABO-type switching during an MTP. Policies varied considerably between responding laboratories, but most (384 of 704, 55%) required 2 ABO types to match before switching from universal to recipient-specific blood components. Additional safety measures used in a minority of these protocols included reaction strength criteria (103 of 704, 15%), on-call medical director approval (41 0f 704, 5.8%), universal red cell unit number limits (12 of 704, 1.7%), or the presence of a mixed field (3 of 704, 0.4%). Conclusions.--This survey reveals that significant heterogeneity exists regarding the available approaches for ABO-type switching during an MTP. Specific expert guidance regarding this issue is very limited, and best practices have not yet been established or rigorously investigated., In the United States, many hospitals have now adopted massive transfusion protocols (MTPs) to ensure that patients with life-threatening hemorrhage receive red cells and plasma in a safe, timely, evidence-based, [...]

Context.--The Kleihauer-Betke (KB) test is validated for estimating the dose of Rh immune globulin needed for Rh-negative pregnant females. However, some clinicians are also ordering the test for Rh-positive women. The degree to which this practice occurs is unknown. Objective.--To evaluate the number of laboratories that perform the KB test on Rh-positive pregnant women, and to establish current ordering practices for this indication. Design.--We added 9 supplemental questions regarding KB test use for fetomaternal hemorrhage to the 2016 College of American Pathologists proficiency test survey. We also reviewed the available literature regarding the diagnostic utility of the KB test for Rh-positive women. Results.--A total of 1578 surveys were evaluated and revealed that 52% (824) of respondents perform these tests for Rh-positive women, and more than 50% (440 of 819; 53.7%) of these laboratories report that the results for Rh-positive women are treated as important or very important. Conclusions.--The KB test is commonly used for Rh-positive women, and the information obtained from the test is considered as urgent and important. However, the available literature in support of this practice is still nonconclusive. doi: 10.5858/arpa.2018-0523-CP, In the United States, nearly all (96.0%) quantitative assays for fetal red blood cells in maternal circulation are performed using several commercially marketed kits for an acid-elution assay, also known [...]

Context.--Plasma transfusion guidelines support patient care and safety, management of product wastage, and compliance; yet, there is little information across multiple institutions about use of and adherence to plasma transfusion guidelines. Objective.--To survey multiple institutions regarding their plasma transfusion guidelines and compliance, plasma wastage rates, and incidence of transfusion reactions associated with plasma transfusion. Design.--The College of American Pathologists QProbes model was used to collect data from 89 participating institutions. Each site was asked to provide data relevant to its most recent 40 adult patient plasma transfusion episodes, and complete a questionnaire regarding plasma transfusion guidelines, utilization and wastage of plasma, and transfusion reactions related to plasma transfusion. Results.--The participating institutions reported a total of 3383 evaluable plasma transfusion episodes with transfusion of 9060 units of plasma. Compliance with institution-specific guidelines was seen in 3018 events (89%). Pretransfusion and posttransfusion coagulation testing was done in 3281 (97%) and 3043 (90%) of these episodes, respectively. Inappropriate criteria were noted for more than 100 transfusion episodes. Thirty-two plasma transfusion episodes (1%) were associated with a transfusion reaction. Serious and fatal reactions were reported. Median plasma wastage rate for the year preceding the study was 4.5%. Conclusions.--Most participating institutions are compliant with plasma transfusion guidelines based on published references, supported by appropriate testing. With transfusions for indications that lack evidence of efficacy and incidence of transfusion reactions, there is an ongoing role for transfusion service leaders to continue to update and monitor plasma transfusion practices. doi: 10.5858/ARPA.2016-0047-CP, Evaluation of transfusion practices serves multiple roles, primary among them patient safety and compliance in support of patient safety. Transfusion is a lifesaving medical therapy, albeit one that is dependent [...]

* Context.--Incorrectly labeled patient blood specimens create opportunities for laboratory testing personnel to mistake one patient's specimen for a specimen from a different patient. Transfusion of blood that is typed on specimens that are mislabeled can result in acute hemolytic transfusion reactions. Objective.--To assess the rates of blood bank ABO typing specimens that are mislabeled and/or contain blood belonging to another patient (so-called wrong blood in tube [WBIT]), and to compare these rates with those determined in a similar study performed in 2007. Design.--Participants enrolled in this College of American Pathologists Q-Probes study for the first quarter of 2015 tallied the number of mislabeled and WBIT ABO blood typing specimens. Outcome measurements were the number of mislabeled and WBIT instances per 1000 specimens. We also evaluated the effects of various practice characteristics, in particular the use of bar coding, on the outcome measurements. Results.--A total of 30 institutions submitting data on 41 333 ABO blood typing specimens recorded aggregate rates of 7.4 instances of mislabeling (306 specimens) and 0.43 instances of WBIT (10 of 23 234) per 1000 specimens submitted. Mislabeling rates were lower in institutions requiring that specimens be labeled with patients' birth dates than those that did not. The rates of specimen mislabeling and WBIT were otherwise unassociated with any of the other practice variables evaluated. Conclusions.--The rates of ABO blood typing specimen mislabeling and WBIT are not statistically different from those determined in a similar study performed in 2007 (P = .94 and P = .10). The use of bar coding was not associated with lower mislabeling (P = .80) or WBIT rates (P = .79). (Arch Pathol Lab Med. 2017;141:255-259; doi: 10.5858/arpa.2016-0167-CP), Incorrectly labeled patient blood specimens create opportunities for laboratory testing personnel to mistake one patient's specimen for a specimen from a different patient. Transfusion of blood that is typed on [...]

Context.--Most information on compliance with audit criteria for red blood cell (RBC) transfusions comes from single institutions; few studies have compared practices among many hospitals. Objective.--To survey a cross-section of hospitals in 2008 for criteria and compliance with RBC transfusion guidelines, using the College of American Pathologists Q-Probes format. Design.--One hundred twenty-eight hospitals, representing about 4.5% (724 332 of 16 212 000) of all annual RBC usage in the United States, provided information on their RBC audit practices and their recent rates of compliance. They also each examined 50 RBC transfusion episodes for compliance with their guidelines. Results.--The participants' median, pretransfusion hemoglobin thresholds for audit review were 8.0 to 8.9 g/dL for most clinical settings and 9.0 to 9.9 g/dL for patients with underlying cardiopulmonary disease. For the transfusion episodes examined, 60% (2063 of 6518) were for a single unit. The median of the institutional averages for pretransfusion hemoglobin was 8.1 g/dL, and the median rate of compliance was 69% (range, 0%-100%). Involvement by a pathologist or transfusion medicine expert in the audit system was associated with more-strict audit criteria and better compliance. Conclusions.--Median hemoglobin thresholds for RBC transfusion audits were somewhat higher than currently evolving recommendations, but opportunities for improvement were provided by expert involvement and by the growing frequency of 1-unit transfusions. (Arch Pathol Lab Med. 2015; 139:351-355; doi: 10.5858/arpa.2013-0756-CP), More than 13 million units of red blood cells (RBCs) were transfused in the United States in 2011.1 The medical indications for these transfusions have received increased scrutiny in recent [...]

Context.--During the past 25 years, the College of American Pathologists' (CAP) Q-Probes program has been available as a subscription program to teach laboratorians how to improve the quality of clinical laboratory services. Objective.--To determine the accomplishments of the CAP Q-Probes program. Design.--We reviewed Q-Probes participant information, study data and conclusions, author information, and program accomplishments. Results.--During this time 117 Q-Probes clinical pathology studies were conducted by 54 authors and coauthors, 42 899 laboratories enrolled from 24 countries, 98 peer-reviewed publications occurred and were cited more than 1600 times, and the studies were featured 59 times in CAP Today. The most frequent studies (19) focused on turnaround times for results or products at specific locations (emergency department, operating room, inpatients, outpatients), specific diseases (acute myocardial infarction, urinary tract), availability for specific events such as morning rounds or surgery, a specific result (positive blood cultures), and a method on how to use data for improvement (stat test outliers). Percentile ranking of study participants with better performance provided benchmarks for each study with attributes statistically defined that influenced improved performance. Other programs, such as an ongoing quality improvement program (Q-Tracks), a laboratory competency assessment program, a pathologist certification program, and an ongoing physician practice evaluation program (Evalumetrics), have been developed from Q-Probes studies. Conclusions.--The CAP's Q-Probes program has made significant contributions to the medical literature and has developed a worldwide reputation for improving the quality of clinical pathology services worldwide. (Arch Pathol Lab Med. 2014; 138:1141-1149; doi: 10.5858/arpa.2014-0150-OA), Before the word benchmark escaped into the variety and imprecision of common usage, it was a surveyor's technical term. Surveyors cut a mark into some durable material, a rock, wall, [...]

* Context.--Rh(D)-negative women with a large fetomaternal hemmorrahage (FMH) from an Rh(D)-positive fetus are at risk for anti-D alloimmunization if they do not receive adequate Rh immune glbulin (RhIG). Determination of the adequate RhIG dose for these women is a critical laboratory procedure for protecting their future Rh(D)-positive children. Objective.--To determine how often laboratories recommended an inaccurate dose of RhIG for excess FMH. Design.--Nearly 1600 laboratories using the College of American Pathologists' proficiency testing for fetal red blood cell detection were surveyed to determine (1) their calculation method and (2) the number of RhIG doses recommended for a survey specimen, based on their measured percentage of fetal red blood cells. We surveyed nearly 1450 laboratories for their accuracy in determining RhIG dose, using 2 common calculation methods we provided. Results.--The AABB Technical Manual method was used by 67% of responding laboratories. However, 20.7% of laboratories using this method would have recommended an inaccurate dose of RhIG--11.5% too much and 9.2% too little--for the level of FMH reported in the survey specimen. If all laboratories had used the common recommendation of 300 [micro]g/30 mL of fetal blood present, 2% would have recommended RhIG doses too low for the volume of FMH they measured. In 3 of the 4 calculation exercises we provided, 20% to 30% of laboratories underestimated the necessary dose of RhIG. Conclusions.--Based on our surveys, some mothers with excess FMH may be receiving inaccurate doses of RhIG. Laboratories performing quantification of FMH should review their procedures and training for calculating RhIG dosage. (Arch Pathol Lab Med. 2009;133:465-469), Rh immune globulin (RhIG) provides prophylaxis against alloimmunization to the D blood group antigen in Rh(D)-negative patients who are exposed to Rh(D)-positive red blood cells (RBCs) by pregnancy or transfusion. [...]