Karina Rodriguez-Capote

Utility of Urine Myoglobin for the Prediction of Acute Renal Failure in Patients with Suspected Rhabdomyolysis: A Systematic Review

BACKGROUND Urine myoglobin continues to be used as a marker of rhabdomyolysis, particularly to assess risk of developing acute renal failure and evaluate treatment success. We sought to determine the predictive validity of urine myoglobin (uMb) for acute renal failure (ARF) in patients with suspected rhabdomyolysis. METHODS We performed a broad systemic review of the literature from January 1980 to December 2006 using the search terms myoglobin

Analytical Evaluation of the Diazyme Glycated Serum Protein Assay on the Siemens ADVIA 1800: Comparison of Results Against HbA1c for Diagnosis and Management of Diabetes

AND (renal OR ARF OR kidney). Only primary studies published in English where uMb measurement was related to ARF were included. RESULTS Of 1602 studies screened, 52 met all selection criteria. The studies covered a wide spectrum of etiologies for rhabdomyolysis, dissimilar diagnostic criteria for ARF and rhabdomyolysis, and various methods of uMb measurement and were mostly case series (n = 32). There was poor reporting on the uMb method, and 17 studies failed to provide any information about the method. The reporting of clinical criteria for ARF with respect to timing, description, performance, and interpretation also lacked adequate detail for replication. Eight studies (total 295 patients) had data for 2-by-2 tables. Sensitivity of the uMb test was 100% in 5 of the 8 studies, specificity varied widely (15% to 88%), and CIs around these measures were high. Pooling of data was not possible because of study heterogeneity. CONCLUSIONS There is inadequate evidence evaluating the use of uMb as a predictor of ARF in patients with suspected rhabdomyolysis.

Identification of Hb Wayne and its effects on HbA1c measurement by 5 methods.

Background: Hemoglobin A1c (HbA1c) is considered the gold standard for assessment of glycemic control in diabetic patients. HbA1c is inadequate in individuals homozygous or compound heterozygous for hemoglobin variants or in conditions with an altered red blood cell turnover. In these cases glycated albumin (GA) is proposed as an alternative assay. We aimed to evaluate the analytical performance of the Diazyme glycated serum protein (GSP) assay on an automated analyzer, to establish a reference interval (RI), and to compare from a clinical perspective, GSP/GA with glycated Hb (glyHb) results. Methods: Validation studies followed the CLSI guidelines and included precision, linearity, interferences, concordance of results with glyHb, and RI calculation. GSP was analyzed on representative samples with previously ordered HbA1c and albumin from the Dyna LIFE DX laboratory. Samples from patients with bisalbuminemia, hemoglobinopathies, and multiple myeloma were also included. Results: Within-run and total imprecision was <3.0% at both levels of control, analytical sensitivity was 5.31 μmol/L, and linearity was verified from 10 to 1150 μmol/L (total allowable error of 5%). Clinical concordance between %GA and glyHb was substantial (n = 175, R2 = .91, kappa = .78, P = .167). GSP RI was 160 to 340 μmol/L or if expressed as %GA 10.5 to 17.5%. Conclusion: Analytical performance of the Diazyme GSP assay on the Siemens ADVIA 1800 is acceptable for clinical use. The RI obtained was higher than that suggested by the manufacturer.

A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy.

BACKGROUND The World Health Organization and the American and Canadian Diabetes Associations approved HbA1c >6.5% as diagnostic for type 2 diabetes mellitus (T2DM). Hb variants and/or their chemically modified species can interfere with HbA1c measurements. We recently described a patient with Hb Wayne trait who was misdiagnosed with T2DM based on falsely elevated HbA1c. Hb Wayne is a clinically silent variant that exists as two isoforms: Hb Wayne I (Asn 139) and Hb Wayne II (Asp 139). METHODS Hemoglobinopathy investigation was performed by HPLC (Bio-Rad VARIANT-II), alkaline and acid electrophoresis (Sebia Hydrasis2), capillary zone electrophoresis (Sebia CAPILLARYS2™) and DNA sequencing. HbA1c was measured by five methods. RESULTS Hb Wayne eluted as two small fractions with retention times of 1.0 and 1.46min on the HPLC (Bio-Rad VARIANT-II). Alkaline gel and capillary electrophoresis showed two small bands migrating faster than HbA. Hb Wayne generated spuriously high results on the Bio-Rad VARIANT-II Turbo 2.0, no results on the Tosoh G8, and did not interfere with either the Sebia CAPILLARYS2™ or immunoassays from Roche (tinaquant) and Siemens (Bayer DCA2000+). Based on the Hb Wayne HPLC profile of 3 patients, an algorithm was developed to facilitate its detection, which identified 9 additional patients with Hb Wayne trait. CONCLUSIONS We characterize Hb Wayne by chromatographic and electrophoretic techniques and show the effect of Hb Wayne on five common HbA1c methodologies. We developed a quality assurance tool to assist in detecting Hb Wayne trait during HbA1c analysis on the Bio-Rad VARIANT-II™ Turbo 2.0.

Stability of specific IgE antibodies to common food and inhalant allergens

OBJECTIVES To report the finding of a novel double heterozygous hemoglobinopathy, the coinheritance of Hb Fontainebleau (α-chain variant) with HbD-Punjab (β-chain variant) discovered upon investigation of unexplained microcytosis in an infant. DESIGN AND METHODS Hemoglobinopathy investigation was performed by high performance liquid chromatography (HPLC) using the β-thalassemia Short Program on the Bio-Rad Variant II(TM) followed by gel electrophoresis at alkaline and acid pH (Sebia Hydrasys 2 Electrophoresis System) and molecular diagnostic testing. This study complied with our institutional board ethics requirements. RESULTS HPLC and electrophoresis suggested a complex α- and β-chain hemoglobinopathy with presumptive identification of the beta Hb variant as Hb D-Punjab. DNA sequencing analysis revealed the presence of a double heterozygous status for Hb Fontainebleau/Hb D-Punjab. CONCLUSIONS In this paper we report the coinheritance of Hb Fontainebleau with Hb D-Punjab.

Erroneous Diabetes Diagnosis: A Case of HbA1c Interference

OBJECTIVE To determine the optimum storage temperature for serum allergen specific IgE antibodies (sIgE) to common food and inhalant allergens. METHODS Patient sera with sIgE concentrations ≥0.7kIUA/l were pooled accordingly: pool 1-peanut and hazelnut, pool 2-egg white, cows milk and cod fish, pool 3-soy, wheat and shrimp and pool 4-dust mite Dermatophagoides farinae, dog dander, cat dander, Timothy grass pollen, and silver birch pollen. Aliquots stored frozen, refrigerated and at room temperature were tested in duplicate (Phadia ImmunoCAP® 250) over two weeks. The relative difference was calculated for each sIgE as a percentage of the initial value and compared to the analytical reference change value. RESULTS Minimal effects on specimen stability were noted for all sIgE analyzed under the three storage conditions tested in this study. All changes observed in sIgE concentrations were related to the assay variability and not to sample deterioration. CONCLUSION Serum allergen specific IgE concentrations are stable at all temperatures studied for up to 17days.

The use of fructosamine in cystic fibrosis-related diabetes (CFRD) screening

A 66-year-old Caucasian female was referred for specialist follow-up of her treatment-refractory type 2 diabetes. The diagnosis was made based on two consecutive HbA1c results >6.5% (48 mmol/mol) in accordance with the Canadian Diabetes Association and the American Diabetes Association guidelines (1,2). Fasting glucose was normal and hyperglycemic symptoms were absent at diagnosis. The patient’s hematological indices were normal and she was unaware of any family history of hemoglobinopathy. Her glycemic control proved difficult to manage, with persistently elevated HbA1c (10.8–11.2% [95–99 mmol/mol]) despite treatment with metformin and, eventually, insulin glargine. Further, with treatment, the patient began to experience symptoms of episodic hypoglycemia. A fasting glucose of 84.6 mg/dL (4.8 mmol/L) obtained at the same time as an HbA1c of 11.2% (99 mmol/mol) triggered suspicion of interference. As all of the HbA …

Candidate recommendations for protein electrophoresis reporting from the Canadian Society of Clinical Chemists Monoclonal Gammopathy Working Group

OBJECTIVE To determine whether serum fructosamine correlates with glycemic control and clinical outcomes in patients being screened for cystic fibrosis-related diabetes (CFRD). METHODS Fructosamine and percent predicted forced expiratory volume in 1s (FEV1) were measured in patients undergoing a 2h oral glucose tolerance test (OGTT) for CFRD screening. Fractional serum fructosamine (FSF) was calculated as fructosamine/total protein. RESULTS FSF exhibited a positive correlation with 2h OGTT results (r2=0.3201, p=0.009), and ROC curve analysis suggested that FSF can identify patients with an abnormal OGTT (AUC=0.840, p=0.0002). FSF also exhibited a negative correlation with FEV1 (r2=0.3732, p=0.035). Patients with FSF≥3.70μmol/g had significantly lower FEV1 (median 47%) compared to those with FSF<3.70μmol/g (median 90%; p=0.015). CONCLUSIONS FSF correlated with both OGTT results and FEV1, and reliably identified patients with abnormal OGTT results. This simple blood test shows potential as an effective tool in CFRD screening.

Evaluation of thyroid test utilization through analysis of population-level data

Protein electrophoresis is commonly used as an aid in the diagnosis of monoclonal gammopathies and is performed in many laboratories in Canada and throughout the world. However, unlike many other diagnostic tests, there is limited guidance for standardization and neither guidance nor specific recommendations for clinical reporting of serum (SPE) or urine (UPE) protein electrophoresis and immunotyping available in the literature. Therefore, a Canadian effort was undertaken to recommend standards that cover all aspects of clinical reporting with an ultimate goal towards reporting standardization. The Canadian Society of Clinical Chemists (CSCC) Monoclonal Gammopathy Interest Group (MGIG), which is composed of CSCC members with an interest in protein electrophoresis, has formed a Monoclonal Gammopathy Working Group (MGWG) to take initial steps towards standardization of SPE, UPE and immunotyping. Candidate standardization recommendations were developed, discussed and voted upon by the MGWG. Candidate recommendations that achieved 90% agreement are presented as consensus recommendations. Recommendations that did not achieve 90% consensus remain candidate recommendations and are presented with accompanying MGWG discussion. Eleven consensus recommendations along with candidate recommendations for nomenclature, protein fraction reporting, test utilization, interference handling and interpretive reporting options are presented.

Hemoglobin Constant Spring exhibits prolonged ex vivo stability when assessed by HPLC.

Abstract: Background: Inappropriate laboratory test utilization can result in unnecessary patient testing and increased healthcare costs. While several thyroid function tests are available, thyroid-stimulating hormone (TSH) is recommended as the first-line test for investigating and monitoring thyroid dysfunction. We evaluate thyroid test utilization in Northern Alberta in terms of testing patterns, frequencies, and reflex cutpoints. Methods: This retrospective study analyzed thyroid test requests from January to December 2014. Each request was designated as appropriate or potentially inappropriate as per clinical practice guidelines and Choosing Wisely recommendations, and the frequencies of each testing pattern were calculated. Sub-analysis was performed to categorize testing patterns based on physician specialty. The number of test requests per patient was determined to assess the appropriateness of testing frequency. Receiver operating characteristic (ROC) curves were generated to define optimal TSH cutpoints for automatic reflex to FT4 testing. Results: Of 752,217 test requests, approximately 10% were potentially inappropriate in terms of testing patterns. Free thyroxine (FT4) and free triiodothyronine (FT3) requested with TSH accounted for 59% of all potentially inappropriate test requests, and 49% of requests from endocrinologists (ENDO) were potentially inappropriate, occurring most frequently among those with less experience. Excessive testing frequencies were observed in 869 patients, accounting for 9382 test requests. Adjustment of our TSH reflex cutpoint would significantly increase specificity for identifying a low FT4 without compromising sensitivity. Conclusions: This study suggests that questionable testing patterns, excessive testing frequencies, and suboptimal reflexive testing cutpoints contribute to inappropriate thyroid test utilization.