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* Context.--Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios. Objective.--To evaluate the performance of DOACspecific assays for various concentrations [...]

Context.--As pharmacogenetic testing is incorporated into routine care, it is essential for laboratories to provide accurate and consistent results. Certified laboratories must successfully complete proficiency testing. Objectives.--To understand and examine trends in participation and performance of laboratories participating in the College of American Pathologists pharmacogenetic proficiency testing surveys. Design.--Results from College of American Pathologists pharmacogenetic proficiency testing challenges from 2012 through 2017 were reviewed for concordance with expected genotype and phenotype for each sample (intended responses). Results.--Laboratories correctly reported results for 96.7% to 100% of samples with no variants. Excluding CYP2D6, laboratories correctly detected and reported variant alleles for each gene (93.7%-99.2% correct). CYP2D6 showed lower concordance, with 83.1% of laboratories reporting the intended genotype across all samples; however, in many cases, the laboratories that did not report a variant allele did not test for that allele. Among laboratories reporting the intended genotype, most successfully reported the intended phenotype (85.9%99.0%). Conclusions.--Although laboratories are generally performing well, there is room for additional improvement, particularly for challenging genes, such as CYP2D6. Efforts in the field of pharmacogenomics to recommend alleles that should be included in clinical tests, identify reference materials, and standardize translation from genotype to phenotype may address some of the remaining variability in results. (Arch Pathol Lab Med. 2020;144:1057-1066; doi: 10.5858/arpa.2019-0478-CP), The application of genetic data to inform drug and dose selection decisions, known as pharmacogenetics (PGx), has received a growing level of attention from patients, wellness proponents, payers, regulatory bodies, [...]

Context.--The College of American Pathologists (CAP) developed proficiency testing for platelet function assays by using blood collected by the participant added to challenge tubes containing either saline (normal) or tirofiban (abnormal). Objective.--To analyze platelet function proficiency testing for Platelet Function Analyzer PFA-100, platelet aggregation, PlateletWorks, and PlateletMapping. Design.--Proficiency testing data from 2012-2016 were analyzed. Results.--For PFA-100, a total of 1200 laboratories participated; the coefficient variation (CV) of cartridge closure times was 22% (saline); 44,952 of 45,616 survey responses (99%) provided an interpretation, and 42,934 of 44,952 (96%) were correct. For optical platelet aggregation, 190 laboratories participated; the CV was 17% (saline), 7444 of 7813 survey responses (95%) provided an interpretation, and 7015 of 7444 (94%) were correct. For PlateletWorks, 60 laboratories participated; the CV was 3% to 11% (saline); 2412 of 2454 survey responses (98%) provided an interpretation, and 1207 of 1276 (95%) were correct for adenosine diphosphate (ADP) and 936 of 1136 (82%) for collagen. For PlateletMapping, 200 laboratories participated. For ADP, 1128 of 2697 survey responses (42%) provided an interpretation, but only 927 of 1128 (82%) were correct. For arachidonic acid, 1139 of 2604 survey responses (44%) provided an interpretation and 964 of 1139 (85%) were correct. Conclusions.--CAP is the first to provide proficiency testing for platelet aggregation, PlateletWorks, and PlateletMapping. Platelet aggregation, PFA-100, and PlateletWorks using ADP as an agonist performed well with more than 90% of laboratories providing an interpretation and a similar number providing correct results. PlateletWorks using collagen and PlateletMapping showed worse interpretive accuracy than the other methods. (Arch Pathol Lab Med. 2019;143:472-482; doi: 10.5858/arpa.2017-0556-CP), Platelets perform multiple functions related to hemostasis and can be activated by multiple pathways; thus, no single platelet function test can assess all aspects of platelet function or diagnose all [...]

* Context.--Statistical literacy can be defined as understanding the statistical tests and terminology needed for the design, analysis, and conclusions of original research or laboratory testing. Little is known about the statistical literacy of clinical or anatomic pathologists. Objective.--To determine the statistical methods most commonly used in pathology studies from the literature and to assess familiarity and knowledge level of these statistical tests by pathology residents and practicing pathologists. Design.--The most frequently used statistical methods were determined by a review of 1100 research articles published in 11 pathology journals during 2015. Familiarity with statistical methods was determined by a survey of pathology trainees and practicing pathologists at 9 academic institutions in which pathologists were asked to rate their knowledge of the methods identified by the focused review of the literature. Results.--We identified 18 statistical tests that appear frequently in published pathology studies. On average, pathologists reported a knowledge level between 'no knowledge' and 'basic knowledge' of most statistical tests. Knowledge of tests was higher for more frequently used tests. Greater statistical knowledge was associated with a focus on clinical pathology versus anatomic pathology, having had a statistics course, having an advanced degree other than an MD degree, and publishing research. Statistical knowledge was not associated with length of pathology practice. Conclusions.--An audit of pathology literature reveals that knowledge of about 12 statistical tests would be sufficient to provide statistical literacy for pathologists. On average, most pathologists report they can interpret commonly used tests but are unable to perform them. Most pathologists indicated that they would benefit from additional statistical training. (Arch Pathol Lab Med. 2017;141:279-287; doi: 10.5858/arpa.2016-0200-OA), The practice of both clinical and anatomic pathology requires familiarity with statistical concepts. The use of sophisticated statistical methods is vital for the modern academic pathologist from nearly all pathology [...]

* Antiphospholipid antibodies are directed against phospholipid-protein complexes and include lupus anticoagulant, anticardiolipin antibodies, and anti-beta-2 glycoprotein I antibodies. Antiphospholipid antibody syndrome is a common cause of acquired thrombophilia and is characterized by venous or arterial thromboembolism or pregnancy morbidity and the presence of antiphospholipid antibodies. Antibodies should be demonstrable on at least 2 occasions separated by 12 weeks. Heterogeneity of the autoantibodies and absence of gold standard assays makes interpretation of laboratory results a challenge for both laboratorians and clinicians. This review discusses the key laboratory and clinical aspects of antiphospholipid antibody syndrome. Particular focus is given to lupus anticoagulant detection, in view of recently updated laboratory guidelines. (Arch Pathol Lab Med. 2011;135:1092-1096), The antiphospholipid antibody syndrome (APS) is defined by thrombotic events and/or obstetric complications and the presence of antiphospholipid antibodies (APAs) detected in patient plasma. Antiphospholipid antibodies are acquired autoantibodies directed [...]

Context.--Accurate quantitation of bone marrow plasma cells is an important component in the diagnosis and posttreatment assessment of plasma cell dyscrasias. Although flow cytometry is sometimes used for this purpose and can rapidly evaluate many cells, the accuracy of flow-based plasma cell quantitation compared with morphologic assessment (currently the gold standard) is uncertain as direct comparison studies have not been previously reported. Objective.--To determine how percentages of plasma cells in diagnostic aspirate smears quantitated by morphologic assessment relate to percentages of plasma cells quantified by flow cytometry. Design.--Thirty bone marrow cases with 10% or more plasma cells and leukemia/lymphoma flow cytometry immunophenotyping studies were identified from our hematopathology database. The Wright-stained aspirate smears, marrow biopsy sections, and flow cytometry histograms were reviewed. Results.--Morphologically determined plasma cell percentages from the diagnostic aspirate smears were consistently higher than those determined by flow cytometry. Much of this difference appeared to be related to differences in sample quality. However, the cellular processing involved in performing flow cytometry also appeared to reduce plasma cell percentages in many cases. Conclusions.--This study helps define the limitations of flow cytometry for quantitating plasma cell loads in marrow aspirate specimens that may significantly affect the diagnosis or assessment of treatment response., The diagnosis and classification of plasma cell dyscrasias typically require quantitation of plasma cell numbers, along with correlation of clinical, radiographic, laboratory, and pathologic findings. (1) For example, a diagnosis [...]

Context.--Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios. Objective.--To evaluate the performance of DOAC-specific assays for various concentrations of dabigatran and rivaroxaban, assess the interlaboratory variability in measurement of these DOACs, and investigate the responsiveness of the routine clotting assays to various concentrations of these oral anticoagulants. Design.--College of American Pathologists proficiency testing survey data from 2013 to 2016 were summarized and analyzed. Results.--For dabigatran, the interlaboratory coefficient of variation (CV) of ecarin chromogenic assay was broad (ranging from 7.5% to 29.1%, 6.3% to 15.5%, and 6.8% to 9.0% for 100-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The CV for diluted thrombin time for dabigatran was better overall (ranging from 11.6% to 17.2%, 9.3% to 12.3, and 7.1% to 11.2% for 100 ng/mL, 200 ng/mL, and 400 ng/mL, respectively). The rivaroxaban-calibrated anti-Xa assay CVs also showed variability (ranging from 11.5% to 22.2%, 7.2% to 10.9%, and 6.4% to 8.1% for 50-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed variable dose- and reagent-dependent responsiveness to DOACs: PT was more responsive to rivaroxaban and aPTT to dabigatran. The undiluted thrombin time showed maximum prolongation across all 3 dabigatran concentrations, making it too sensitive for drug-level monitoring, but supporting its use as a qualitative screening assay. Conclusions.--DOAC-specific assays performed reasonably well. While PT and aPTT cannot be used safely to determine DOAC degree of anticoagulation, a normal thrombin time excludes the presence of dabigatran. [ABSTRACT FROM AUTHOR]