bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Utility of Factor V Leiden (R506Q) Testing for the Diagnosis and Management of Thromboembolic Disorders
Authors: Press Richard D. , Bauer Kenneth A. , Kujovich Jody L. , Heit John A. 
Published: January 2021

AbstractObjective.—To review the current state of the art regarding the role of the clinical laboratory in diagnostic testing for the factor V Leiden (FVL) thrombophilic mutation (and other protein C resistance disorders), and to generate, through literature reviews and opinions of recognized thought-leaders, expert consensus recommendations on methodology and diagnostic, prognostic, and management issues pertaining to clinical FVL testing.Data Sources, Extraction, and Synthesis.—An initial thorough review of the medical literature and of current best clinical practices by a panel of 4 experts followed by a consensus conference review, editing, and ultimate approval by the majority of a panel of 28 additional coagulation laboratory experts.Conclusions.—Consensus recommendations were generated for topics of direct clinical relevance, including (1) defining those patients (and family members) who should (and should not) be tested for FVL; (2) defining the preferred FVL laboratory testing methods; and (3) defining the therapeutic, prophylactic, and management ramifications of FVL testing in affected individuals and their family members. As FVL is currently the most common recognized familial thrombophilia, it is hoped that these recommendations will assist laboratorians and clinicians caring for patients (and families) with this common mutation.
Laboratory Issues in Diagnosing Abnormalities of Protein C, Thrombomodulin, and Endothelial Cell Protein C Receptor
Authors: Kottke-Marchant Kandice , Comp Philip 
Published: January 2021

Abstract
Objective.—To review the current understanding of the pathophysiology of protein C deficiency and its role in congenital thrombophilia. Recommendations for diagnostic testing for protein C function and concentration, derived from the medical literature and consensus opinions of recognized experts in the field, are included, specifying whom, how, and when to test. The role of related proteins, such as thrombomodulin and endothelial protein C receptor, is also reviewed.
Data Sources.—Review of the published medical literature.
Data Extraction and Synthesis.—A summary of the medical literature and proposed testing recommendations were prepared and presented at the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. After discussion at the conference, consensus recommendations presented in this manuscript were accepted after a two-thirds majority vote by the participants.
Conclusions.—Protein C deficiency is an uncommon genetic abnormality that may be a contributing cause of thrombophilia, often in conjunction with other genetic or acquired risk factors. When assay of protein C plasma levels is included in the laboratory evaluation of thrombophilia, a functional amidolytic protein C assay should be used for initial testing. The diagnosis of protein C deficiency should be established only after other acquired causes of protein C deficiency are excluded. A low protein C level should be confirmed with a subsequent assay on a new specimen. Antigenic protein C assays may be of benefit in subclassification of the type of protein C deficiency. The role of thrombomodulin and endothelial cell protein C receptor in thrombosis has yet to be clearly established, and diagnostic testing is not recommended at this time.
A Review of the Technical, Diagnostic, and Epidemiologic Considerations for Protein S Assays
Authors: Goodwin Andrew J. , Rosendaal Frits R. , Kottke-Marchant Kandice , Bovill Edwin G. 
Published: January 2021

Abstract
Objectives.—To review the state of the art relating to protein S deficiency as a risk factor for thrombosis and to make recommendations regarding the use of protein S measurements in the assessment of thrombotic risk in individual patients and families.
Data Sources, Extraction, and Synthesis.—Selection criteria were developed for the inclusion of publications from 1985 to 2001 based on the relevant literature concerned with the systematic review of diagnostic tests. Minimal selection criteria were agreed on and the articles stratified into level 1 if they met these criteria and level 2 if they did not meet these criteria. The included articles were reviewed by the authors and abstracted onto predetermined data collection forms. These forms were then scored and recommendations based on level 1 studies. As described elsewhere, results of discussions at the College of American Pathologists Conference XXXVI on Diagnostic Issues in Thrombophilia were used to revise the manuscript into its final form.
Conclusions.—Consensus was reached on 16 recommendations for the use of protein S assays in the assessment of thrombotic risk in individuals and families. Two themes run through the conclusions. First, protein S assays are the most technically problematic of the assays reviewed at this conference. Second, only 2 papers evaluating the diagnostic use of protein S assays met our level 1 inclusion criteria. These 2 problems point out the need for better standardized assays and rigorous studies of the diagnostic utility of these assays.
Factor XIII Polymorphisms and Venous Thromboembolism
Authors: Francis Charles W. 
Published: January 2021

AbstractObjective.—To review the relationship between factor XIII polymorphisms and venous thromboembolism.Methods.—Review of the medical literature using computerized databases and secondary sources identified through reviews of bibliographies.Data Synthesis.—Plasma factor XIII is the precursor of a transglutaminase that cross-links fibrin, thereby altering its properties, including resistance to fibrinolysis. It is, therefore, biologically plausible that alterations in factor XIII activity could affect thrombosis risk. There are 4 common polymorphic forms of factor XIII that differ among ethnic groups. The Val34Leu polymorphism results in an amino acid change near the thrombin cleavage site that may alter the rate of activation. Several case-control studies have investigated the relation of the Val34Leu polymorphism to venous thromboembolism. Some have shown a potentially protective effect of this polymorphism, but the association is not consistent.Conclusion.—Evidence is conflicting regarding the association of the factor XIII Val34Leu polymorphism with risk of venous thromboembolism, and further studies are needed before screening for this polymorphism can be recommended for evaluation of thrombophilia.
Elevated Hemostatic Factor Levels as Potential Risk Factors for Thrombosis
Authors: Chandler Wayne L. , Rodgers George M. , Sprouse Jason T. , Thompson Arthur R. 
Published: January 2021

Abstract
Objectives.—To review the state of the art relating to elevated hemostatic factor levels as a potential risk factor for thrombosis, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and to make recommendations for the use of specific measurements of hemostatic factor levels in the assessment of thrombotic risk in individual patients.
Data Sources.—Review of the medical literature, primarily from the last 10 years.
Data Extraction and Synthesis.—After an initial assessment of the literature, key points were identified. Experts were assigned to do an in-depth review of the literature and to prepare a summary of their findings and recommendations. A draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia prior to the conference. Each of the key points and associated recommendations was then presented for discussion at the conference. Recommendations were accepted if a consensus of the 27 experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form.
Conclusions.—Consensus was reached on 8 recommendations concerning the use of hemostatic factor levels in the assessment of thrombotic risk in individual patients. Detailed discussion of the rationale for each of these recommendations is presented in the article. This is an evolving area of research. While routine use of factor level measurements is not recommended, improvements in assay methodology and further clinical studies may change these recommendations in the future.
Platelet Count Monitoring and Laboratory Testing for Heparin-Induced Thrombocytopenia
Authors: Warkentin Theodore E. 
Published: January 2021

Abstract
Objective.—Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that paradoxically is associated with a brief but dramatically increased risk for thrombosis (transient acquired thrombophilia). The objective of this article is to provide practical recommendations for platelet count monitoring in patients receiving heparin, as well as for selection of laboratory assays to detect pathogenic HIT antibodies.
Study Selection.—Relevant literature that focused on frequency and timing of HIT in various clinical settings and that dealt with laboratory testing for HIT antibodies was critically appraised.
Data Extraction and Synthesis.—The author prepared a preliminary manuscript including recommendations that was presented to participants at the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia (November 10, 2001). Support of at least 70% of conference participants was required for recommendations to be adopted.
Conclusions.—The risk of immune HIT varies depending on the type of heparin (unfractionated heparin greater than low-molecular-weight heparin) and patient population (surgical greater than medical). Thus, the intensity of platelet count monitoring should be stratified depending on the clinical situation. Platelet count monitoring should focus on the period of highest risk (usually days 5 to 10 after starting heparin) and should use an appropriate platelet count baseline (generally, the highest platelet count beginning 4 days after start of heparin). However, earlier platelet count monitoring is appropriate if the patient received heparin within the past 100 days, as already circulating HIT antibodies can cause rapid-onset HIT with heparin reexposure. Although both antigen and (washed platelet) activation assays are very sensitive for detecting clinically significant HIT antibodies, activation assays have greater diagnostic specificity for clinical HIT.
Trophoblast Apoptosis in Human Placenta at Term as Detected by Expression of a Cytokeratin 18 Degradation Product of Caspase
Authors: Austgulen Rigmor , Chedwick Lisa , Isaksen Christina Vogt , Vatten Lars , Craven Catherine 
Published: January 2021

Abstract
Context.—Apoptosis occurs in the normal placenta. The monoclonal antibody M30 is directed against a novel epitope of cytokeratin 18 (CK18) that is formed by caspase cleavage early in the apoptotic cascade, and this antibody may therefore be useful for evaluating trophoblast apoptosis.
Objective.—We undertook the present study to evaluate the use of monoclonal antibody M30 to assess trophoblast apoptosis in placenta at term.
Methods.—We stained paraffin-embedded placental tissues from 15 deliveries at term with M30. We compared positive M30 staining and CK18 staining (as detected by a monoclonal antibody directed against CK18) of trophoblasts in serial slides. We also compared apoptotic rates as detected by M30 and TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling) in 7 of the placentas.
Results.—In fields of villous tissue, most M30-positive cells were CK18-positive syncytiotrophoblasts. Approximately half of M30-positive cells occurred as focal positive staining in the syncytial layer, and half occurred as abundant staining of syncytiotrophoblasts in areas with increased intervillous or perivillous fibrinoid. We found very few M30-positive cells in villous stroma. In decidual/basal plate tissues, most (two thirds) of the M30-positive cells were CK18-positive extravillous trophoblasts, whereas one third were syncytiotrophoblasts of anchoring villi. Since TUNEL detects apoptosis in both epithelial and nonepithelial cells, more cells were positively stained with TUNEL than with M30 in some tissue fields. However, our observations suggest that M30 was more sensitive than TUNEL in recognizing apoptotic trophoblasts and had less nonspecific staining than TUNEL.
Conclusion.—We recommend the use of monoclonal antibody M30 for apoptosis studies in placental tissues. This antibody is easy to handle, the staining obtained seems specific, and the nonspecific staining seems negligible.
Positive Predictive Value of a Point-of-Care Testing Strategy on First-Draw Specimens for the Emergency Department–Based Detection of Acute Coronary Syndromes
Authors: Kratz Alexander , Januzzi James L. , Lewandrowski Kent B. , Lee-Lewandrowski Elizabeth 
Published: January 2021

Abstract
Context.—The rapid and accurate diagnosis of the etiology of chest pain is of central importance in the triage of patients presenting to emergency departments. The “first-draw” sensitivity of serum cardiac markers is known to be low on initial presentation; however, less is understood regarding the predictive value of a positive test in this situation.
Objective.—To determine the ability of a critical pathway combining medical history and physical examination, electrocardiographic findings, point-of-care testing, and central laboratory data to accurately predict the presence of acute coronary ischemia.
Methods.—We investigated the positive predictive value of a testing algorithm for first-draw specimens in clinical practice, combining a qualitative, point-of-care, triple-screen testing panel for cardiac markers, including myoglobin, creatine kinase–MB, and cardiac troponin I, with confirmation of the rapid assay in the central hospital laboratory by quantitative assays for creatine kinase–MB and cardiac troponin T.
Results.—While a positive result on any of the individual cardiac markers of the point-of-care test had a positive predictive value for the acute coronary syndrome of only 36% (creatine kinase–MB, 41%; myoglobin, 36%; and troponin I, 65%), the positive predictive value for the diagnosis of acute coronary syndrome increased to 76% if all 3 point-of-care markers were simultaneously positive. The positive predictive value for acute coronary syndrome for a positive confirmatory result in the hospital laboratory for either creatine kinase–MB or cardiac troponin T was 61%. Among those patients with a positive marker on both the point-of-care test and the laboratory test, a careful retrospective review of the clinical history (with exclusion of patients with nonischemic cardiac pathologies and renal insufficiency) increased the positive predictive value of this algorithm to 98%.
Conclusions.—Our data suggest that qualitative, point-of-care, triple-screen cardiac marker testing of patients with chest pain at initial presentation may exhibit relatively low positive predictive values. Positive predictive value can be significantly improved by rapid confirmation in the hospital laboratory and careful review of clinical findings.
Evaluation of a Dual Hemoglobin A2/A1c Quantitation Kit on the Bio-Rad Variant II Automated Hemoglobin Analyzer
Authors: Lafferty John D. , McFarlane Andrew G. , Chui David H. K. 
Published: January 2021

Abstract
Context.—Quantitation of hemoglobin (Hb) A1c and investigation of hemoglobinopathy on the Bio-Rad Variant analyzers require a switch between 2 separate kits that is time consuming and causes errors.
Objective.—Evaluation of a new Variant II HbA2/HbA1c Dual kit capable of both Hb A1c quantitation and hemoglobinopathy investigation on a single kit.
Design.—We evaluated Hb A1c, Hb A2, and Hb F quantitation for precision, linearity, and correlation with current methodology. We also evaluated detection of Hb variants and correlation of Hb Barts quantitation.
Setting.—Hamilton Regional Laboratory Medicine Program, Provincial Hemoglobinopathy Laboratory, St Joseph's Healthcare Site, Hamilton, Ontario.
Patients.—Patient blood samples submitted for Hb A1c quantitation or hemoglobinopathy investigation.
Main Outcome Measures.—Precision, linearity, linear regression, and reference interval validation.
Results.—We provide tables and figures illustrating precision, linearity, linear regression, and quantitation of Hb variants. We validated reference intervals for Hb A1c, Hb A2, and Hb F.
Conclusions.—The dual kit provides precise Hb A1c, Hb A2, and Hb F quantitation. The results show good linearity and correlate well with the results of current methods. We detected all clinically important Hb variants and a wide variety of rare variants. The dual kit has several advantages: it eliminates the need for extensive kit switch over; improves utility for newborn screening because of its quantification of Hb Barts; permits quantification of Hb A1c using the β-Thal method; and eliminates the need for separate Hb A2 reference intervals for patients with Hb S because of its accurate quantitation of Hb A2 in the presence of Hb S.
Adult Rhabdoid Renal Cell Carcinoma
Authors: Shannon Beverley , Wisniewski Zdzisilaw Stan , Bentel Jacqueline , Cohen Ronald J. 
Published: January 2021

Abstract
Background.—Pediatric rhabdoid tumor of the kidney is regarded as a distinct neoplasm, whereas rhabdoid differentiation in adult renal cell carcinoma is usually found in association with conventional (clear cell) tumor, from which it is thought to evolve.
Objective.—To further characterize the rhabdoid phenotype in adult renal cell carcinoma and to determine its origin by genetic analysis.
Design.—We performed histologic, immunophenotypic, and genetic analyses on 5 cases of adult renal cell carcinoma with rhabdoid differentiation, 3 samples of adjacent conventional (clear cell) tumor, and 6 conventional (clear cell) control tumors.
Results.—Rhabdoid tumors differed from conventional (clear cell) carcinoma as follows: (1) macroscopically, rhabdoid tumors were solid white uniform masses; (2) microscopically, they had large rhabdoid cells with abundant eosinophilic cytoplasm, reduced lipid content, and the absence of a branching vascular pattern; and (3) biologically, they had a high metastatic potential. Despite these differences, loss of chromosome 3p in both the rhabdoid and clear cell carcinoma samples from 1 patient suggested a clonal origin. An identical mutation of the VHL gene in both rhabdoid and clear cell tumor samples from 2 patients confirmed a clonal origin for the histologically distinct tumor types in those cases.
Conclusion.—Adult rhabdoid renal cell carcinoma can in some cases arise from conventional (clear cell) renal carcinoma and should be considered a clinically important form of renal cell carcinoma separate from, but analogous to, sarcomatoid change.
Parathyroid Gland Involvement by Papillary Carcinoma of the Thyroid Gland
Authors: Tang Weihua , Kakudo Kennichi , Nakamura Yasushi , Nakamura Misa , Mori Ichiro , Morita Shinji , Miyauchi Akira 
Published: January 2021

Abstract
Objective.—To describe the phenomenon of parathyroid gland involvement by thyroid carcinoma and to explore its clinicopathologic significance.
Design.—We reviewed the clinicopathologic features and described the histopathologic characteristics of 20 cases of parathyroid involvement found in a series of 911 papillary thyroid carcinomas.
Results.—Parathyroid involvement occurred in 3 patterns: (1) direct invasion from the main tumor with an infiltrative growth, (2) invasion of the parathyroid gland with an expansive growth and formation of a pseudocapsule between the carcinoma and the parathyroid gland, and (3) metastatic deposition within the parathyroid gland itself. Among the 20 cases, 6 (30%) had primary tumors measuring 1 cm or less, and 14 (70%) had primary tumors measuring more than 1 cm. The cases with smaller primary tumors had a comparatively lower rate of nodal metastasis (50% vs 100%, P = .02). Furthermore, none of the cases with smaller primary tumors had invasion of extrathyroid structures other than parathyroid gland, but such invasion was common among the cases with larger primary tumors (0% vs 71%, P = .01).
Conclusion.—To the best of our knowledge, this is the first report showing that parathyroid involvement occurs in papillary thyroid carcinomas even in the early stage of the disease.
Allergic Transfusion Reactions
Authors: Domen Ronald E. , Hoeltge Gerald A. 
Published: January 2021

Abstract
Context.—Allergic reaction to transfusion is common. However, the review of a large series of allergic transfusion reactions has not been performed.
Objective.—To review a large series of allergic transfusion reactions.
Design.—A retrospective review of all reported and evaluated transfusion reactions during a 9-year period at 1 institution was performed. Associated clinical signs and symptoms were evaluated.
Setting.—Large, tertiary-care teaching hospital.
Results.—A total of 1613 adverse reactions to transfusion were evaluated. Allergic transfusion reactions accounted for 17% (273 of 1613) of the transfusion reactions. Severe allergic reactions (anaphylaxis, anaphylactoid signs and symptoms, and/or hypotension) were observed in 21 patients (7.7% of allergic reactions, or 1.3% of all transfusion reactions). Serum tryptase, a marker for anaphylaxis, was measured in 1 patient and determined to be borderline elevated. Five patients experienced allergic transfusion reactions to autologous red cell transfusions. One patient experienced hives during the transfusion of a major ABO mismatched red blood cell. A wide variety of skin manifestations were observed, but 26 (9.5%) patients did not have skin manifestations. Allergic transfusion reactions were estimated to occur in approximately 1 in 4124 blood components transfused, or 1 in 2338 transfusion episodes. Severe allergic reactions occurred in approximately 1 in 30 281 transfusions. No deaths directly attributable to transfusion were observed in this patient group.
Conclusions.—The clinical presentation of allergic transfusion reactions was quite variable, and the pathophysiology remains unclear. Recommendations for clinical evaluation and therapy remain problematic and often empirical.