Isohemagglutinin titration in pooled and apheresis platelets.

BACKGROUND: Platelet inventory constraints necessitate ABO-incompatible platelet transfusion. Many minimize the hemolytic impact by confirming low titre (LT) donor isohemagglutinins. This process is costly. Pathogen-reduced platelets (PRP) in platelet additive solutions (PAS) will dilute plasma and decrease high-titre isohemagglutinins (HT). We determined the proportion of HT platelets and incompatible transfusions for units suspended in plasma to reassess the need for titres following introduction of PRP/PAS. STUDY DESIGN AND METHODS: Our titre method is manual tube (1:50) dilution of platelet supernatant from apheresis or whole blood derived buffy coat pools suspended in plasma, tested with A1/B red cells. Testing included 49,058 pooled and 11,738 apheresis platelets over 4 years. The HT proportion, rate of out-of-group transfusions, and hemolytic reactions were determined. The impact of PAS dilution was estimated. RESULTS: Totally 60,796 platelet units were tested. Group O pooled and group B apheresis platelets had HT in 6.6% and 5.7%, respectively. Group A pooled and apheresis platelets included 2% with HT. Approximately 25% of platelets transfused were ABO-incompatible and no hemolytic reactions were reported. Based on the proportions of PAS-E and plasma for PRP platelets, plasma from each donor comprises 11 mL (6% of total volume) vs 20-257 mL in untreated pools. PAS-E will replace and dilute residual plasma by at least 50%. DISCUSSION: Rare platelet pools may demonstrate HT. PRP platelets with PAS will reduce titres and may abrogate the need for titration. A strategy of group specific transfusion or transfusion of group A PRP platelet transfusions may be a safe alternative.

An unsupervised learning approach to identify immunoglobulin utilization patterns using electronic health records.

BACKGROUND: Managing Canada's immunoglobulin (Ig) product resource allocation is challenging due to increasing demand, high expenditure, and global shortages. Detection of groups with high utilization rates can help with resource planning for Ig products. This study aims to uncover utilization subgroups among the Ig recipients using electronic health records (EHRs). METHODS: The study included all Ig recipients (intravenous or subcutaneous) in Calgary from 2014 to 2020, and their EHR data, including blood inventory, recipient demographics, and laboratory test results, were analyzed. Patient clusters were derived based on patient characteristics and laboratory test data using K-means clustering. Clusters were interpreted using descriptive analyses and visualization techniques. RESULTS: Among 4112 recipients, six clusters were identified. Clusters 1 and 2 comprised 408 (9.9%) and 1272 (30.9%) patients, respectively, contributing to 62.2% and 27.1% of total Ig utilization. Cluster 3 included 1253 (30.5%) patients, with 86.4% of infusions administered in an inpatient setting. Cluster 4, comprising 1034 (25.1%) patients, had a median age of 4 years, while clusters 2-6 were adults with median ages of 46-60. Cluster 5 had 62 (1.5%) patients, with 77.3% infusions occurring in emergency departments. Cluster 6 contained 83 (2.0%) patients receiving subcutaneous Ig treatments. CONCLUSION: The results identified data-driven segmentations of patients with high Ig utilization rates and patients with high risk for short-term inpatient use. Our report is the first on EHR data-driven clustering of Ig utilization patterns. The findings hold the potential to inform demand forecasting and resource allocation decisions during shortages of Ig products.

Two approaches to the clinical dilemma of treating TTP with therapeutic plasma exchange in patients with a history of anaphylactic reactions to plasma.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare but serious disease caused by autoantibody-mediated deficiency in von Willebrand factor (VWF) cleaving protease, ADAMTS-13. The primary acute treatment is therapeutic plasma exchange (TPE). However, some patients can develop allergic/anaphylactic reactions to the replacement (i.e., donor) plasma over time. Two potential treatment strategies for patients with TTP who demonstrate severe allergic reactions to plasma used for exchange were examined. METHODS: Two patients with TTP exacerbations who developed severe allergic reactions to donor plasma were identified. One patient's TPE was re-initiated with Octaplas, a lot-batched solvent and detergent treated, type-specific, pooled donor plasma product. The other patient was exchanged with primarily albumin, followed by slow incremental exposures to donor plasma to mitigate exposures and allergic risks. Both patients were assessed for anaphylaxis. RESULTS: Both treatment strategies were successful in preventing any further clinically significant allergic/anaphylactic reactions and facilitated both patients' TTP remissions. CONCLUSIONS: Based on our experience with two similar patients with TTP exacerbations and history of anaphylactic reactions to plasma during TPE, we have identified two possible treatment protocols to achieve remission in this clinical dilemma. Substituting Octaplas for standard plasma or, alternatively, using albumin with slowly increasing amounts of standard plasma may help to mitigate the risk of further anaphylactic adverse events. J. Clin. Apheresis 32:158-162, 2017. © 2016 Wiley Periodicals, Inc.

Complex regional pain syndrome and dysautonomia in a 14-year-old girl responsive to therapeutic plasma exchange.

Reflex sympathetic dystrophy, also known as complex regional pain syndrome (CRPS), has recently been shown to be associated with autoantibodies against ß2-adrenergic and muscarinic M2 receptors. In addition to pain and sudomotor/vasomotor symptoms, dysautonomia is also observed in a subset of CRPS patients. Despite its severity, there are few effective therapies for CRPS described to date. We report a case of a 14-year-old girl with CRPS of her right leg and dysautonomia (gastroparesis, postural tachycardia) refractory to multiple therapies, successfully treated with therapeutic plasma exchange (TPE) with albumin replacement. The patient, who has serum anti ß2-adrenergic and muscarinic M2 receptor autoantibodies in addition to nicotinic acetylcholine receptor ganglionic autoantibodies, underwent an initial course of five TPEs over a 2-week period. She demonstrated a clinical response to TPE as manifested by a rapid improvement in her fatigue and gastroparesis, with a gradual yet significant improvement in her leg pain and sudomotor/vasomotor flares. Following the loading procedures, the patient was treated with rituximab. She continues to require periodic TPE to maintain a remission, with additional immunosuppression being considered long term. Although further studies are needed, TPE (in combination with immunosuppression) may be an appropriate therapy for CRPS patients with detectable autoantibodies, as it is for better characterized diseases with autoantibodies against neuronal surface receptors such as myasthenia gravis or Lambert Eaton myasthenic syndrome. J. Clin. Apheresis 31:368-374, 2016. © 2015 Wiley Periodicals, Inc.

Methoxypyrazine analysis and influence of viticultural and enological procedures on their levels in grapes, musts, and wines.

This review discusses the factors that affect the concentrations of methoxypyrazines (MPs) and the techniques used to analyze MPs in grapes, musts, and wines. MPs are commonly studied pyrazines in food science due to their contribution of aroma and flavor to numerous vegetables such as peas and asparagus. They are described as highly odorous compounds with a very low olfactory threshold. The grape varietals that exhibit green or herbaceous aromas that are characteristic of MPs are predominantly Vitis vinifera cv. Cabernet Sauvignon and Sauvignon Blanc, but include others. The most extensively studied MPs include 3-isobutyl-2-methoxypyrazine, 3-isopropyl-2-methoxypyrazine, and 3-sec-butyl-2-methoxypyrazine. It outlines the significance of methoxypyrazines in grapes, musts, and wines in terms of the concentrations that are capable of contributing their sensory characteristics to wines. This review discusses methods for analyzing MPs including gas chromatography-mass spectroscopy (one or two dimension) and high-performance liquid chromatography, the appropriate extraction techniques, and the efficacy of these methods. Additionally, this review explores factors that affect pyrazine content of grapes, must, and wines, such as the effects of different viticultural practices, effects of light exposure and grape maturation, climate, soil, the multi-colored Asian lady beetle and the effects of different vinification processes.

Break the fast? Update on patient preparation for cholesterol testing.

OBJECTIVE: To provide an update on the clinical usefulness of nonfasting versus fasting lipid testing to improve patient compliance, patient safety, and clinical assessment in cholesterol testing. QUALITY OF EVIDENCE: Recommendations are identified as supported by good, fair, and poor (conflicting or insufficient) evidence, according to the classifications adopted by the Canadian Task Force on Preventive Health Care. MAIN MESSAGE: Screening for dyslipidemia as a risk factor for coronary artery disease and management of lipid-lowering medications are key parts of primary care. Recent evidence has questioned the fasting requirement for lipid testing. In population-based studies, total cholesterol, high-density lipoprotein cholesterol, and non-low-density lipoprotein cholesterol all varied by an average of 2% with fasting status. For routine screening, nonfasting cholesterol measurement is now a reasonable alternative to a fasting cholesterol measurement. For patients with diabetes, the fasting requirement might be an important safety issue because of problems with hypoglycemia. For the monitoring of triglyceride and low-density lipoprotein cholesterol levels in patients taking lipid-lowering medications, fasting becomes more important. CONCLUSION: Fasting for routine lipid level determinations is largely unnecessary and unlikely to affect patient clinical risk stratification, while nonfasting measurement might improve patient compliance and safety.

Laboratory tests, interpretation, and use of resources: a program to introduce the basics.

PROBLEM ADDRESSED: The overuse of laboratory testing has increased rapidly and is contributing to the financial strain on the health care system in Canada. Moreover, a substantial proportion of ordered tests are unnecessary. In a search of all the Canadian family physician residency programs, none lists laboratory training as mandatory or as an optional elective in its curriculum. OBJECTIVE OF PROGRAM: To introduce family medicine residents to appropriate and efficient use of laboratory tests. PROGRAM DESCRIPTION: The program was run as a series of identical 4-hour small group sessions to facilitate discussion and laboratory tours. The curriculum focused on 7 key topics: problems associated with laboratory testing, sources of laboratory errors, definitions of normal and abnormal test results, appropriate use of laboratory requisition forms, laboratory quality assurance methods, laboratory collection processes, and costs of common laboratory tests. Residents were taken to a patient specimen collection site for a tour and introduction, followed by approximately 2 hours of didactic sessions, and ending with a tour of a large tertiary care testing facility. CONCLUSION: The program was very well received by family medicine residents and resulted in a substantial increase in residents' self-assessed knowledge of the 7 topics covered in the curriculum. It is hoped that this program will fill an important gap in residency training and support residents' competency in the "selectivity" domain of training.

Reproducibility of histological cell type in high-grade endometrial carcinoma.

Subclassification of endometrial carcinoma according to histological type shows variable interobserver agreement. The aim of this study was to assess specifically the interobserver agreement of histological type in high-grade endometrial carcinomas, recorded by gynecological pathologists from five academic centers across Canada. In a secondary aim, the agreement of consensus diagnosis with immunohistochemical marker combinations was assessed including six routine (TP53, CDKN2A (p16), ER, PGR, Ki67, and VIM) and six experimental immunohistochemical markers (PTEN, ARID1A, CTNNB1, IGF2BP3, HNF1B, and TFF3). The paired interobserver agreement ranged from κ 0.50 to 0.63 (median 0.58) and the intraobserver agreement from κ 0.49 to 0.67 (median 0.61). Consensus about histological type based on morphological assessment was reached in 72% of high-grade endometrial carcinomas. A seven-marker immunohistochemical panel differentiated FIGO grade 3 endometrioid from serous carcinoma with a 100% concordance rate compared with the consensus diagnosis. More practically, a three-marker panel including TP53, ER, and CDKN2A (p16) can aid in the differential diagnosis of FIGO grade 3 endometrioid from endometrial serous carcinoma. Our study demonstrates that the inter- and intraobserver reproducibility of histological type based on morphology alone are mostly moderate. Ancillary techniques such as immunohistochemical marker panels are likely needed to improve diagnostic reproducibility of histological types within high-grade endometrial carcinomas.

Immunoglobulin utilization in Canada: a comparative analysis of provincial guidelines and a scoping review of the literature.

BACKGROUND: Canada has high immunoglobulin (IG) product utilization, raising concerns about appropriate utilization, cost and risk of shortages. Currently, there is no national set of standardized IG guidelines, and considerable variations exist among the existing provincial guidelines. The aims of this study were: (1) to compare the existing Canadian provincial guidelines on the use of IG products to identify their consistencies and differences and (2) to examine the existing research in Canada on IG supply and utilization following the establishment of IG guidelines to understand the scope of research and pinpoint the gaps. METHODS: A comparative analysis accounted for the differences across provincial IG guidelines. We highlighted similarities and differences in recommendations for medical conditions. A scoping review of citations from MEDLINE, PubMed, Scopus and Embase databases was conducted for studies published from January 01, 2014, to April 12, 2023. RESULTS: While provincial guidelines represented a considerable overlap in the medical conditions delineated and relatively uniform dose calculations, numerous differences were observed, including in recommendation categories, provision of pediatric dosing, and divergent recommendations for identical conditions based on patient demographics. The scoping review identified 29 studies that focused on the use of IG in Canada. The themes of the studies included: IVIG utilization and audits, the switch from IVIG to SCIG, patient satisfaction with IVIG and/or SCIG, the economic impact of self-administered SCIG versus clinically administered IVIG therapy, and the efficacy and cost-effectiveness of alternative medications to IG treatment. CONCLUSION: The differences in guidelines across provinces and the factors influencing IVIG/SCIG use, patient satisfaction, and cost savings are highlighted. Future research may focus on clarifying costs and comparative effectiveness, exploring factors influencing guideline adherence, and evaluating the impact of updated guidelines on IG use and patient outcomes.

Risk Assessment of Hospitalized Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Infected Patients Using Laboratory Data and Immune Cell Morphologic Assessment.

CONTEXT.­: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious agent, with the propensity to cause severe illness. While vaccine uptake has been increasing in recent months, many regions remain at risk of significant coronavirus disease 19 (COVID-19)-related health care burden. Health systems will continue to benefit from the availability of a variety of clinical and laboratory models when other triaging models are equivocal. OBJECTIVE.­: To validate previously reported clinical laboratory abnormalities seen in COVID-19 patients and identify what laboratory parameters might be outcome predictive. DESIGN.­: We undertook an observational study of hospital-admitted COVID-19 patients (n = 113), looking at a broad selection of clinical, laboratory, peripheral blood smear, and outcome data during discrete discovery and validation periods from March 2020 to November 2020. RESULTS.­: We confirmed the findings of previous studies noting derangement of a variety of laboratory parameters in COVID-19 patients, including peripheral blood morphologic changes. We also devised a simple-to-use decision tree by which patients could be risk stratified on the basis of red blood cell count, creatinine, urea, and atypical plasmacytoid lymphocyte ("covidocyte") count. This outcome classifier performed comparably to the World Health Organization clinical classifier and the neutrophil-lymphocyte ratio. CONCLUSIONS.­: Our data add to the increasing number of studies cataloguing laboratory changes in COVID-19 and support the clinical utility of incorporating blood morphologic assessment in the workup of hospitalized COVID-19 patients.

Factors Associated with Hyponatremia in Patients Newly Prescribed Citalopram: A Retrospective Observational Study.

BACKGROUND: Hyponatremia is a common and under-recognized adverse drug reaction of selective serotonin re-uptake inhibitor (SSRI) antidepressants. Despite its clinical importance, there are few large-scale studies on the factors associated with hyponatremia. OBJECTIVE: The aim of this study was to determine the incidence of hyponatremia and to identify patient factors associated with hyponatremia in a large, population-based cohort initiating new prescriptions for citalopram. METHODS: We included all patients with a new prescription for citalopram during 2010-2017, inclusive, with baseline and post-initiation serum sodium values available. Data were obtained from an Alberta Health Pharmacy database to identify new citalopram prescriptions. Laboratory values for patients with new prescriptions were obtained from linked Calgary Laboratory Services data. Incident hyponatremia was defined as serum sodium level < 135 mmol/L, following prescription initiation. Associations were determined by performing Cox regression with time-varying covariate analysis, with the development of hyponatremia as the dependent variable. RESULTS: A total of 19,679 patients with new prescriptions were identified; 12,842 females and 6837 males. The mean age was 55.48 years (SD 21.35). Of these patients, 3250 (16.5%) developed hyponatremia, 1996 (15.5% of) females and 1254 (18.3% of) males (p = 0.002). Cox regression showed significant associations of hyponatremia with lower baseline sodium (HR 0.788), older age (HR 1.029), thiazide diuretic use (HR 1.141), and male sex (HR 1.168). Pharmaceutical manufacturer or strength of citalopram did not have significant effects on the development of hyponatremia. CONCLUSION: This study provides additional data on the predictors of hyponatremia among patients initiating citalopram therapy. We report a 16.5% incidence of hyponatremia after starting citalopram treatment, and significant new findings include a higher incidence in males. This is the first published incidence of hyponatremia following the initiation of citalopram treatment across all ages in Canada.

Therapeutic Plasma Exchange and Its Impact on Drug Levels: An ACLPS Critical Review.

OBJECTIVES: To examine and summarize the current literature on the effects of therapeutic plasma exchange on medication levels. METHODS: Literature review was performed via searches of the Cochrane Database and PubMed-MEDLINE (1996 to August 2016) looking for all case reports, case series, and human randomized controlled trials involving therapeutic plasma exchange (TPE)-associated drug removal. RESULTS: Approximately 60 peer-reviewed articles were identified with the majority being case reports; no randomized controlled trials were identified. These reports and the authors' own experiences were used to derive practical guidance regarding the effect of TPE on circulating drug levels. CONCLUSIONS: There were several limitations with existing studies, many of which relate to procedural and/or clinical properties of patients undergoing TPE. As such, additional studies are needed before definitive guidelines can be established. There is clear need for development of consensus and additional investigations in this domain.

Guidelines for the review of pathology in the research context.

BACKGROUND: Research involving a retrospective review of a patient's pathology could change the original pathologist's diagnosis and alter management, treatment, and prognosis. In the interests of patient safety, this review diagnosis needs to be validated and the impact on patient care assessed before disclosure to the patient occurs. The Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP) did not have a guideline for managing this scenario. METHODS: Under CAP-ACP executive committee sponsorship, a working group was formed to develop a comprehensive guideline for this scenario. To inform the document's development, the group carried out an extensive literature review, surveyed practices in laboratories across Canada, and reviewed practices in pathology colleges in the United Kingdom, Australasia, and the United States. The Tricouncil Interagency in Research Ethics in Canada, the Canadian Medical Protective Association and members of the CAP-ACP were consulted. RESULTS: Neither the published literature nor the trans-Canadian laboratory survey identified a guideline document. The Royal College of Pathologists of Australasia had a policy and procedure for the scenario; other colleges did not. The guideline developed by the working group listed roles for the ethics committee, researcher, original pathologist, and laboratory in managing the scenario and incorporated the input acquired in the consultation phase. The final document was endorsed in 2012 by the CAP-ACP executive committee and is available on the website (available from: http://www.cap-acp.org/psqa.cfm). CONCLUSION: The guideline is anchored in principles of patient safety and can be used to minimize and/or manage changes in the pathologic diagnosis which arise from a research-based review of prior pathology reports.

Fasting time and lipid levels in a community-based population: a cross-sectional study.

BACKGROUND: Although current guidelines recommend measuring lipid levels in a fasting state, recent studies suggest that nonfasting lipid profiles change minimally in response to food intake and may be superior to fasting levels in predicting adverse cardiovascular outcomes. The objective of this study was to investigate the association between fasting times and lipid levels. METHODS: Cross-sectional examination of laboratory data, including fasting duration (in hours) and lipid results, was performed over a 6-month period in 2011 in a large community-based cohort. Data were obtained from Calgary Laboratory Services, Calgary, Alberta, Canada, the sole supplier of laboratory services for Calgary and surrounding areas (source population, 1.4 million persons). The main outcome measures were mean levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglycerides for fasting intervals from 1 hour to more than 16 hours. After differences in individual ages were controlled for, linear regression models were used to estimate the mean levels of cholesterol subclasses at different fasting times. RESULTS: A total of 209,180 individuals (111,048 females and 98,132 males) were included in the study. The mean levels of total cholesterol and high-density lipoprotein cholesterol differed little among individuals with various fasting times. The mean calculated low-density lipoprotein cholesterol levels showed slightly greater variations of up to 10% among groups of patients with different fasting intervals, and the mean triglyceride levels showed variations of up to 20%. CONCLUSION: Fasting times showed little association with lipid subclass levels in a community-based population, which suggests that fasting for routine lipid levels is largely unnecessary.