Carbamylated hemoglobin (carbHb) is reported to interfere with measurement and interpretation of ... more Carbamylated hemoglobin (carbHb) is reported to interfere with measurement and interpretation of HbA(1c) in diabetic patients with chronic renal failure (CRF). There is also concern that HbA1c may give low results in these patients due to shortened erythrocyte survival. We evaluated the effect of carbHb on HbA(1c) measurements and compared HbA(1c) with glycated albumin (GA) in patients with and without renal disease to test if CRF causes clinically significant bias in HbA(1c) results by using 11 assay methods. Subjects included those with and without renal failure and diabetes. Each subject's estimated glomerular filtration rate (eGFR) was used to determine the presence and degree of the renal disease. A multiple regression model was used to determine if the relationship between HbA(1c) results obtained from each test method and the comparative method was significantly (p<0.05) affected by eGFR. These methods were further evaluated for clinical significance by using the difference between the eGRF quartiles of >7% at 6 or 9% HbA(1c). The relationship between HbA(1c) and glycated albumin (GA) in patients with and without renal failure was also compared. Some methods showed small but statistically significant effects of eGFR; none of these differences were clinically significant. If GA is assumed to better reflect glycemic control, then HbA(1c) was approximately 1.5% HbA(1c) lower in patients with renal failure. Although most methods can measure HbA(1c) accurately in patients with renal failure, healthcare providers must interpret these test results cautiously in these patients due to the propensity for shortened erythrocyte survival in renal failure.
The diversity of methods used to measure glycohemoglobins (GHb) makes it difficult to compare pat... more The diversity of methods used to measure glycohemoglobins (GHb) makes it difficult to compare patients' results among laboratories. We reported previously the feasibility of providing comparable results from different assays by use of common calibrators. We here compare results from seven different GHb methods calibrated by use of hemolysates assayed by a precise ion-exchange high-performance liquid-chromatographic (HPLC) method for hemoglobin A1c (HbA1c). Thus, regardless of the GHb species measured by the seven methods, results were referenced to the HbA1c content of the calibrators. Without this calibration, GHb values for single samples varied, e.g., from 4.0% to 8.1% and from 10% to 14.2% in the normal and high ranges, respectively. Calibration decreased between-method variability (single sample ranges of, e.g., 4.8% to 5.4% and 9.4% to 10.2% in the normal and high ranges, respectively) and improved interassay precision. We conclude that this approach to calibration of GHb ...
The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes S... more The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) demonstrated conclusively that risks for complications in patients with diabetes are directly related to glycemic control, as measured by glycohemoglobin (GHB). In 1994, one year after the DCCT results were reported, the American Diabetes Association (ADA) set specific diabetes treatment goals. However, 1993 College of American Pathologists (CAP) Survey results indicated a lack of comparability of GHB test results among methods and laboratories that represented a major obstacle to meaningful implementation of the ADA guidelines. Thus, an AACC subcommittee was formed in 1993 to develop a standardization program that would enable laboratories to report DCCT-traceable GHB results. This program was implemented in 1996 by the National Glycohemoglobin Standardization Program (NGSP) Steering Committee. We review the NGSP process and summarize progress in standardization through ana...
... The following methods/instruments were evaluated: the A1c 2.2 Plus TM Glycohemoglobin Analyze... more ... The following methods/instruments were evaluated: the A1c 2.2 Plus TM Glycohemoglobin Analyzer (Tosoh Medics), the Diamat TM Analyzer System and a Variant TM Hemoglobin Testing System (Bio-Rad Laboratories), the IMx ® Glycated Hemoglobin assay (Abbott ...
To address the question, Do laboratory tests cost money or save money? we have used as a model fo... more To address the question, Do laboratory tests cost money or save money? we have used as a model for discussion a common chronic disease, diabetes mellitus, and a widely used laboratory test, that for glycohemoglobin, a measure of long-term glycemia used to manage diabetic patients. Diabetes mellitus is serious, highly prevalent, and costly. In 1992, $1 of every $7 spent on health in the US was for diabetes, predominantly for treatment of the chronic complications of the disease. The recently completed Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are related to the degree of altered glycemia as quantified by determinations of glycohemoglobin. Thus, use of glycohemoglobin testing for routine diabetes care provides an objective measure of a patient's risk for developing diabetic complications. Results of this test can alert patients and health providers to the need for change in the treatment p...
Journal of diabetes science and technology, Jan 17, 2015
Previous studies have shown interference with HbA1c measurement from the 4 most common heterozygo... more Previous studies have shown interference with HbA1c measurement from the 4 most common heterozygous Hb variants (HbAS, HbAE, HbAC, and HbAD) with some assay methods. Here we examine analytical interference from 49 different less common variants with 7 different HbA1c methods using various method principles. Hb variants were screened using the Bio-Rad Variant or Variant II beta thal short program, confirmed by alkaline and acid electrophoresis, and identified by sequence analysis. The Trinity ultra2 boronate affinity high-performance liquid chromatography (HPLC) method and Roche Tinaquant immunoassay were used as primary and secondary comparative methods, respectively, since these methods are least likely to show interference from Hb variants. Other methods included were the Tosoh G7 and G8, Bio-Rad D-10 and Variant II Turbo, Diazyme Enzymatic, and Sebia Capillarys 2 Flex Piercing. To eliminate any inherent calibration bias, results for each method were adjusted using regression vers...
... Mei Wiedmeyer 1 , Randie Little 1 , V. Lee Grotz 2 , Alethea Tennill 1 , Jack England 1 ... H... more ... Mei Wiedmeyer 1 , Randie Little 1 , V. Lee Grotz 2 , Alethea Tennill 1 , Jack England 1 ... Home page, Blood Home page RM Cohen, RS Franco, PK Khera, EP Smith, CJ Lindsell, PJ ... Home page, Pediatrics Home page DE Williams, BL Cadwell, YJ Cheng, CC Cowie, EW Gregg, LS ...
... a , Barun K. De 2 , Diane Brown 3 , C. Michael Hanbury 4 , James D. Hoyer 5 , W. Garry John 6... more ... a , Barun K. De 2 , Diane Brown 3 , C. Michael Hanbury 4 , James D. Hoyer 5 , W. Garry John 6 , Thomas ... following methods/instruments were evaluated: Cobas INTEGRA 700 Hemoglobin A1c whole blood application (Roche Diagnostics Corporation), Glyco-Tek affinity column ...
... 405 OBSERVATIONS Reduction in Foot Ulcer Incidence Relation to compliance with a prophylactic... more ... 405 OBSERVATIONS Reduction in Foot Ulcer Incidence Relation to compliance with a prophylactic foot care program Diabetic foot lesions are one of the most serious causes of morbidity among diabetic people and often require a long hospital stay. ...
To evaluate the use of GHb as a screening test for undiagnosed diabetes (fasting plasma glucose &... more To evaluate the use of GHb as a screening test for undiagnosed diabetes (fasting plasma glucose > or =7.0 mmol/l) in a representative sample of the U.S. population. The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged > or =20 years. Of these subjects, 7,832 participated in a morning examination session, of which 1,273 were excluded because of a previous diagnosis of diabetes, missing data, or fasting time of <8 h before examination. Venous blood was obtained to measure fasting plasma glucose and GHb in the remaining 6,559 subjects. Receiver operating characteristic curve analysis was used to examine the sensitivity and specificity of GHb for detecting diabetes at increasing GHb cutoff levels. GHb demonstrated high sensitivity (83.4%) and specificity (84.4%) for detecting undiagnosed diabetes at a GHb cutoff of 1 SD above the normal mean. Moderate sensitivity (63.2%) and very high specificity (97.4%) were evident at a GHb cutoff of 2 SD above the normal mean. Sensitivity at this level ranged from 58.6% in the non-Hispanic white population to 83.6% in the Mexican-American population; specificity ranged from 93.0% in the nonHispanic black population to 98.3% in the non-Hispanic white population. GHb is a highly specific and convenient alternative to fasting plasma glucose for diabetes screening. A GHb value of 2 SD above the normal mean could identify a high proportion of individuals with undiagnosed diabetes who are at risk for developing diabetes complications.
To define the relationship between HbA(1c) and plasma glucose (PG) levels in patients with type 1... more To define the relationship between HbA(1c) and plasma glucose (PG) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial (DCCT). The DCCT was a multicenter, randomized clinical trial designed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes. Quarterly HbA(1c) and corresponding seven-point capillary blood glucose profiles (premeal, postmeal, and bedtime) obtained in the DCCT were analyzed to define the relationship between HbA(1c) and PG. Only data from complete profiles with corresponding HbA(1c) were used (n = 26,056). Of the 1,441 subjects who participated in the study, 2 were excluded due to missing data. Mean plasma glucose (MPG) was estimated by multiplying capillary blood glucose by 1.11. Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA(1c). Linear regression analysis, using MPG and HbA(1c) summarized by patient (n = 1,439), produced a relationship of MPG (mmol/l) = (1.98 . HbA(1c)) - 4.29 or MPG (mg/dl) = (35.6 . HbA(1c)) - 77.3, r = 0.82). Among individual time points, afternoon and evening PG (postlunch, predinner, postdinner, and bedtime) showed higher correlations with HbA(1c) than the morning time points (prebreakfast, postbreakfast, and prelunch). We have defined the relationship between HbA(1c) and PG as assessed in the DCCT. Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA(1c) goals.
The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study... more The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) established the importance of hemoglobin A(1c) (Hb A(1c)) as a predictor of outcome in patients with diabetes mellitus. In 1994, the American Diabetes Association began recommending specific Hb A(1c) targets, but lack of comparability among assays limited the ability of clinicians to use these targets. The National Glycohemoglobin Standardization Program (NGSP) was implemented in 1996 to standardize Hb A(1c) results to those of the DCCT/UKPDS. The NGSP certifies manufacturers of Hb A(1c) methods as traceable to the DCCT. The certification criteria have been tightened over time and the NGSP has worked with the College of American Pathologists in tightening proficiency-testing requirements. As a result, variability of Hb A(1c) results among clinical laboratories has been considerably reduced. The IFCC has developed a reference system for Hb A(1c) that facilitates metrological traceability to a higher order. The NGSP maintains traceability to the IFCC network via ongoing sample comparisons. There has been controversy over whether to report Hb A(1c) results in IFCC or NGSP units, or as estimated average glucose. Individual countries are making this decision. Variability among Hb A(1c) results has been greatly reduced. Not all countries will report Hb A(1c) in the same units, but there are established equations that enable conversion between different units. Hb A(1c) is now recommended for diagnosing diabetes, further accentuating the need for optimal assay performance. The NGSP will continue efforts to improve Hb A(1c) testing to ensure that clinical needs are met.
Glycohemoglobin (GHB), reported as hemoglobin (Hb) A(1c), is a marker of long-term glycemic contr... more Glycohemoglobin (GHB), reported as hemoglobin (Hb) A(1c), is a marker of long-term glycemic control in patients with diabetes and is directly related to risk for diabetic complications. HbE and HbD are the second and fourth most common Hb variants worldwide. We investigated the accuracy of HbA(1c) measurement in the presence of HbE and/or HbD traits. We evaluated 23 HbA(1c) methods; 9 were immunoassay methods, 10 were ion-exchange HPLC methods, and 4 were capillary electrophoresis, affinity chromatography, or enzymatic methods. An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of HbE or HbD traits caused a statistically significant difference from HbAA results relative to the boronate affinity HPLC comparative method. Deming regression analysis was performed to determine whether the presence of these traits produced a clinically significant effect on HbA(1c) results with the use of +/-10% relative bias at 6% and 9% HbA(1c) as evaluation limits. Statistically significant differences were found in more than half of the methods tested. Only 22% and 13% showed clinically significant interference for HbE and HbD traits, respectively. Some current HbA(1c) methods show clinically significant interferences with samples containing HbE or HbD traits. To avoid reporting of inaccurate results, ion-exchange chromatograms must be carefully examined to identify possible interference from these Hb variants. For some methods, manufacturers' instructions do not provide adequate information for making correct decisions about reporting results.
Carbamylated hemoglobin (carbHb) is reported to interfere with measurement and interpretation of ... more Carbamylated hemoglobin (carbHb) is reported to interfere with measurement and interpretation of HbA(1c) in diabetic patients with chronic renal failure (CRF). There is also concern that HbA1c may give low results in these patients due to shortened erythrocyte survival. We evaluated the effect of carbHb on HbA(1c) measurements and compared HbA(1c) with glycated albumin (GA) in patients with and without renal disease to test if CRF causes clinically significant bias in HbA(1c) results by using 11 assay methods. Subjects included those with and without renal failure and diabetes. Each subject's estimated glomerular filtration rate (eGFR) was used to determine the presence and degree of the renal disease. A multiple regression model was used to determine if the relationship between HbA(1c) results obtained from each test method and the comparative method was significantly (p<0.05) affected by eGFR. These methods were further evaluated for clinical significance by using the difference between the eGRF quartiles of >7% at 6 or 9% HbA(1c). The relationship between HbA(1c) and glycated albumin (GA) in patients with and without renal failure was also compared. Some methods showed small but statistically significant effects of eGFR; none of these differences were clinically significant. If GA is assumed to better reflect glycemic control, then HbA(1c) was approximately 1.5% HbA(1c) lower in patients with renal failure. Although most methods can measure HbA(1c) accurately in patients with renal failure, healthcare providers must interpret these test results cautiously in these patients due to the propensity for shortened erythrocyte survival in renal failure.
The diversity of methods used to measure glycohemoglobins (GHb) makes it difficult to compare pat... more The diversity of methods used to measure glycohemoglobins (GHb) makes it difficult to compare patients' results among laboratories. We reported previously the feasibility of providing comparable results from different assays by use of common calibrators. We here compare results from seven different GHb methods calibrated by use of hemolysates assayed by a precise ion-exchange high-performance liquid-chromatographic (HPLC) method for hemoglobin A1c (HbA1c). Thus, regardless of the GHb species measured by the seven methods, results were referenced to the HbA1c content of the calibrators. Without this calibration, GHb values for single samples varied, e.g., from 4.0% to 8.1% and from 10% to 14.2% in the normal and high ranges, respectively. Calibration decreased between-method variability (single sample ranges of, e.g., 4.8% to 5.4% and 9.4% to 10.2% in the normal and high ranges, respectively) and improved interassay precision. We conclude that this approach to calibration of GHb ...
The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes S... more The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) demonstrated conclusively that risks for complications in patients with diabetes are directly related to glycemic control, as measured by glycohemoglobin (GHB). In 1994, one year after the DCCT results were reported, the American Diabetes Association (ADA) set specific diabetes treatment goals. However, 1993 College of American Pathologists (CAP) Survey results indicated a lack of comparability of GHB test results among methods and laboratories that represented a major obstacle to meaningful implementation of the ADA guidelines. Thus, an AACC subcommittee was formed in 1993 to develop a standardization program that would enable laboratories to report DCCT-traceable GHB results. This program was implemented in 1996 by the National Glycohemoglobin Standardization Program (NGSP) Steering Committee. We review the NGSP process and summarize progress in standardization through ana...
... The following methods/instruments were evaluated: the A1c 2.2 Plus TM Glycohemoglobin Analyze... more ... The following methods/instruments were evaluated: the A1c 2.2 Plus TM Glycohemoglobin Analyzer (Tosoh Medics), the Diamat TM Analyzer System and a Variant TM Hemoglobin Testing System (Bio-Rad Laboratories), the IMx ® Glycated Hemoglobin assay (Abbott ...
To address the question, Do laboratory tests cost money or save money? we have used as a model fo... more To address the question, Do laboratory tests cost money or save money? we have used as a model for discussion a common chronic disease, diabetes mellitus, and a widely used laboratory test, that for glycohemoglobin, a measure of long-term glycemia used to manage diabetic patients. Diabetes mellitus is serious, highly prevalent, and costly. In 1992, $1 of every $7 spent on health in the US was for diabetes, predominantly for treatment of the chronic complications of the disease. The recently completed Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are related to the degree of altered glycemia as quantified by determinations of glycohemoglobin. Thus, use of glycohemoglobin testing for routine diabetes care provides an objective measure of a patient's risk for developing diabetic complications. Results of this test can alert patients and health providers to the need for change in the treatment p...
Journal of diabetes science and technology, Jan 17, 2015
Previous studies have shown interference with HbA1c measurement from the 4 most common heterozygo... more Previous studies have shown interference with HbA1c measurement from the 4 most common heterozygous Hb variants (HbAS, HbAE, HbAC, and HbAD) with some assay methods. Here we examine analytical interference from 49 different less common variants with 7 different HbA1c methods using various method principles. Hb variants were screened using the Bio-Rad Variant or Variant II beta thal short program, confirmed by alkaline and acid electrophoresis, and identified by sequence analysis. The Trinity ultra2 boronate affinity high-performance liquid chromatography (HPLC) method and Roche Tinaquant immunoassay were used as primary and secondary comparative methods, respectively, since these methods are least likely to show interference from Hb variants. Other methods included were the Tosoh G7 and G8, Bio-Rad D-10 and Variant II Turbo, Diazyme Enzymatic, and Sebia Capillarys 2 Flex Piercing. To eliminate any inherent calibration bias, results for each method were adjusted using regression vers...
... Mei Wiedmeyer 1 , Randie Little 1 , V. Lee Grotz 2 , Alethea Tennill 1 , Jack England 1 ... H... more ... Mei Wiedmeyer 1 , Randie Little 1 , V. Lee Grotz 2 , Alethea Tennill 1 , Jack England 1 ... Home page, Blood Home page RM Cohen, RS Franco, PK Khera, EP Smith, CJ Lindsell, PJ ... Home page, Pediatrics Home page DE Williams, BL Cadwell, YJ Cheng, CC Cowie, EW Gregg, LS ...
... a , Barun K. De 2 , Diane Brown 3 , C. Michael Hanbury 4 , James D. Hoyer 5 , W. Garry John 6... more ... a , Barun K. De 2 , Diane Brown 3 , C. Michael Hanbury 4 , James D. Hoyer 5 , W. Garry John 6 , Thomas ... following methods/instruments were evaluated: Cobas INTEGRA 700 Hemoglobin A1c whole blood application (Roche Diagnostics Corporation), Glyco-Tek affinity column ...
... 405 OBSERVATIONS Reduction in Foot Ulcer Incidence Relation to compliance with a prophylactic... more ... 405 OBSERVATIONS Reduction in Foot Ulcer Incidence Relation to compliance with a prophylactic foot care program Diabetic foot lesions are one of the most serious causes of morbidity among diabetic people and often require a long hospital stay. ...
To evaluate the use of GHb as a screening test for undiagnosed diabetes (fasting plasma glucose &... more To evaluate the use of GHb as a screening test for undiagnosed diabetes (fasting plasma glucose > or =7.0 mmol/l) in a representative sample of the U.S. population. The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged > or =20 years. Of these subjects, 7,832 participated in a morning examination session, of which 1,273 were excluded because of a previous diagnosis of diabetes, missing data, or fasting time of <8 h before examination. Venous blood was obtained to measure fasting plasma glucose and GHb in the remaining 6,559 subjects. Receiver operating characteristic curve analysis was used to examine the sensitivity and specificity of GHb for detecting diabetes at increasing GHb cutoff levels. GHb demonstrated high sensitivity (83.4%) and specificity (84.4%) for detecting undiagnosed diabetes at a GHb cutoff of 1 SD above the normal mean. Moderate sensitivity (63.2%) and very high specificity (97.4%) were evident at a GHb cutoff of 2 SD above the normal mean. Sensitivity at this level ranged from 58.6% in the non-Hispanic white population to 83.6% in the Mexican-American population; specificity ranged from 93.0% in the nonHispanic black population to 98.3% in the non-Hispanic white population. GHb is a highly specific and convenient alternative to fasting plasma glucose for diabetes screening. A GHb value of 2 SD above the normal mean could identify a high proportion of individuals with undiagnosed diabetes who are at risk for developing diabetes complications.
To define the relationship between HbA(1c) and plasma glucose (PG) levels in patients with type 1... more To define the relationship between HbA(1c) and plasma glucose (PG) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial (DCCT). The DCCT was a multicenter, randomized clinical trial designed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes. Quarterly HbA(1c) and corresponding seven-point capillary blood glucose profiles (premeal, postmeal, and bedtime) obtained in the DCCT were analyzed to define the relationship between HbA(1c) and PG. Only data from complete profiles with corresponding HbA(1c) were used (n = 26,056). Of the 1,441 subjects who participated in the study, 2 were excluded due to missing data. Mean plasma glucose (MPG) was estimated by multiplying capillary blood glucose by 1.11. Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA(1c). Linear regression analysis, using MPG and HbA(1c) summarized by patient (n = 1,439), produced a relationship of MPG (mmol/l) = (1.98 . HbA(1c)) - 4.29 or MPG (mg/dl) = (35.6 . HbA(1c)) - 77.3, r = 0.82). Among individual time points, afternoon and evening PG (postlunch, predinner, postdinner, and bedtime) showed higher correlations with HbA(1c) than the morning time points (prebreakfast, postbreakfast, and prelunch). We have defined the relationship between HbA(1c) and PG as assessed in the DCCT. Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA(1c) goals.
The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study... more The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) established the importance of hemoglobin A(1c) (Hb A(1c)) as a predictor of outcome in patients with diabetes mellitus. In 1994, the American Diabetes Association began recommending specific Hb A(1c) targets, but lack of comparability among assays limited the ability of clinicians to use these targets. The National Glycohemoglobin Standardization Program (NGSP) was implemented in 1996 to standardize Hb A(1c) results to those of the DCCT/UKPDS. The NGSP certifies manufacturers of Hb A(1c) methods as traceable to the DCCT. The certification criteria have been tightened over time and the NGSP has worked with the College of American Pathologists in tightening proficiency-testing requirements. As a result, variability of Hb A(1c) results among clinical laboratories has been considerably reduced. The IFCC has developed a reference system for Hb A(1c) that facilitates metrological traceability to a higher order. The NGSP maintains traceability to the IFCC network via ongoing sample comparisons. There has been controversy over whether to report Hb A(1c) results in IFCC or NGSP units, or as estimated average glucose. Individual countries are making this decision. Variability among Hb A(1c) results has been greatly reduced. Not all countries will report Hb A(1c) in the same units, but there are established equations that enable conversion between different units. Hb A(1c) is now recommended for diagnosing diabetes, further accentuating the need for optimal assay performance. The NGSP will continue efforts to improve Hb A(1c) testing to ensure that clinical needs are met.
Glycohemoglobin (GHB), reported as hemoglobin (Hb) A(1c), is a marker of long-term glycemic contr... more Glycohemoglobin (GHB), reported as hemoglobin (Hb) A(1c), is a marker of long-term glycemic control in patients with diabetes and is directly related to risk for diabetic complications. HbE and HbD are the second and fourth most common Hb variants worldwide. We investigated the accuracy of HbA(1c) measurement in the presence of HbE and/or HbD traits. We evaluated 23 HbA(1c) methods; 9 were immunoassay methods, 10 were ion-exchange HPLC methods, and 4 were capillary electrophoresis, affinity chromatography, or enzymatic methods. An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of HbE or HbD traits caused a statistically significant difference from HbAA results relative to the boronate affinity HPLC comparative method. Deming regression analysis was performed to determine whether the presence of these traits produced a clinically significant effect on HbA(1c) results with the use of +/-10% relative bias at 6% and 9% HbA(1c) as evaluation limits. Statistically significant differences were found in more than half of the methods tested. Only 22% and 13% showed clinically significant interference for HbE and HbD traits, respectively. Some current HbA(1c) methods show clinically significant interferences with samples containing HbE or HbD traits. To avoid reporting of inaccurate results, ion-exchange chromatograms must be carefully examined to identify possible interference from these Hb variants. For some methods, manufacturers' instructions do not provide adequate information for making correct decisions about reporting results.
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Papers by C. Rohlfing