Interference of Asfotase Alfa in Immunoassays Employing Alkaline Phosphatase Technology

Abstract Background Asfotase alfa (STRENSIQ®, Alexion Pharmaceuticals, Inc.) is the only approved treatment for patients with pediatric-onset hypophosphatasia, a disease caused by a mutation in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. ALP is often used as signaling system in routine immunoassays. Because asfotase alfa contains the active site of the full ALP enzyme, it can catalyze the substrate as the antibody-conjugated ALP would within an assay. Therefore, its presence in a treated patient’s sample may generate false positive or false negative results. We investigated whether the presence of asfotase alfa within a sample induced interference in immunoassays that utilize ALP or alternative detection systems. Methods Asfotase alfa was added to samples at concentrations from 0.08–5 µg/mL and analysed on various immunoassays following manufacturer’s instructions. Results Asfotase alfa was detected in all ALP assays but ALKP1 (RayBiotech). We observed no changes in normetanephrine and noradrenaline (IBL) at any asfotase alfa concentration. However, asfotase alfa notably interfered in an oxytocin (ENZO) assay in nonextracted samples. Extraction using a C18 column eliminated the interference. No interference was observed on automated analyzers using alternative detection system (COBAS fT4 and TSH; Advia Centaur FSH, fT4; Architect LH; FSH). Immulite 2000 fT4, TSH, testosterone and hCG (ALP-based) showed no interference. However, the presence of asfotase alfa resulted in a dose-dependent increase of Troponin I signal. Conclusion The presence of asfotase alfa must be taken into consideration when analyzing blood samples in treated patients to avoid any risk of misinterpretation of false positive/negative results. It is essential that assays be tested for this possible interference.

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The nitroblue tetrazolium test. An evaluation of the false-positive and false-negative results

Archives of Internal Medicine ◽

10.1001/archinte.133.3.432 ◽

1974 ◽

Vol 133 (3) ◽

pp. 432-436 ◽

Cited By ~ 1

Author(s):

M. E. Campos

Keyword(s):

False Positive ◽

False Negative ◽

Nitroblue Tetrazolium ◽

Negative Results ◽

False Negative Results ◽

Nitroblue Tetrazolium Test ◽

Tetrazolium Test

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Critical Evaluation of Impedance Phlebography for the Diagnosis of Deep Vein Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649161 ◽

1974 ◽

Vol 31 (02) ◽

pp. 273-278

Author(s):

Kenneth K Wu ◽

John C Hoak ◽

Robert W Barnes ◽

Stuart L Frankel

Keyword(s):

Deep Vein Thrombosis ◽

False Positive ◽

False Negative ◽

Critical Evaluation ◽

Original Method ◽

Vein Thrombosis ◽

Negative Results ◽

False Negative Results ◽

Deep Vein ◽

Positive Results

SummaryIn order to evaluate its daily variability and reliability, impedance phlebography was performed daily or on alternate days on 61 patients with deep vein thrombosis, of whom 47 also had 125I-fibrinogen uptake tests and 22 had radiographic venography. The results showed that impedance phlebography was highly variable and poorly reliable. False positive results were noted in 8 limbs (18%) and false negative results in 3 limbs (7%). Despite its being simple, rapid and noninvasive, its clinical usefulness is doubtful when performed according to the original method.

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Thyroid Screening for Early Discharged Infants

PEDIATRICS ◽

10.1542/peds.98.1.41 ◽

1996 ◽

Vol 98 (1) ◽

pp. 41-44

Author(s):

Judy G. Saslow ◽

Ernest M. Post ◽

Carol A. Southard

Keyword(s):

New Jersey ◽

Congenital Hypothyroidism ◽

False Positive ◽

False Negative ◽

Negative Results ◽

Thyroid Screening ◽

False Negative Results ◽

Positive Results

Objective. As neonatal discharge before 24 hours of life becomes commonplace, the rejection of congenital hypothyroidism (CH) screening specimens obtained too early has created the need for numerous additional tests. We sought to determine whether the specimens obtained before 24 hours could be used safely. Methods. During a 31-day period we measured thyrotropin in all thyroid-screening specimens that had been obtained before 24 hours. We also examined the early specimens from every infant diagnosed in New Jersey with CH during 1993 or 1994. Results. Among the 663 specimens, those obtained at or before 12 hours and those from infants with birth weights less than 2500 g had too many low thyroxine results to be useful. Among the 515 specimens obtained at more than 12 to 24 hours from newborns weighing 2500 g or more, 37 (7%) had low thyroxine levels and 12 (2.3%) had thyrotropin levels of 20 µIU/mL (mU/L) or higher. Four hundred seventy-one of the 515 infants had subsequent specimens obtained at more than 24 hours, and none of the results were abnormal. There was no child weighing more than or equal to 2500 g who was diagnosed with CH in 1993 and 1994 whose specimen obtained at 24 hours or less was normal. Conclusions. Accepting specimens obtained at more than 12 to 24 hours from infants weighing 2500 g or more would have resulted in more than the usual number of false-positive results but no false-negative results. This would have decreased the requests for additional specimens by more than 90%.

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Review of Inpatient Thrombophilia Testing at a Tertiary Care Center

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz130.012 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S147-S147

Author(s):

Andrew Hall ◽

Ortega Lopez ◽

Amy Powers

Keyword(s):

Liver Disease ◽

False Positive ◽

Care Center ◽

Thrombotic Event ◽

Tertiary Care ◽

False Negative ◽

Anticoagulation Therapy ◽

Tertiary Care Center ◽

Negative Results ◽

False Negative Results

Abstract Introduction Testing for thrombophilic risk factors is common in patients with thrombosis. However, inpatient hereditary thrombophilia work-ups are prone to false-positive and false-negative results due to concurrent acute phase changes, protein consumption, anticoagulation therapy, and liver disease. A recent ASCP Choosing Wisely guideline recommends against measuring protein C (PC), protein S (PS), or antithrombin III (AT3) to diagnose a hereditary deficiency during an active clotting event. We aimed to review inpatient PC, PS, and AT3 activity assay ordering practices at a tertiary care center. The goal of this study was to determine appropriateness and identify areas for improvement in inpatient thrombophilia ordering practices. Methods A retrospective review of inpatients who underwent thrombophilia testing was performed. Inclusion criteria consisted of adult inpatients with PC, PS, and/or AT3 activity results. Patients for whom AT3 was ordered alone were excluded. The timeframe of testing relative to an acute thrombotic event, anticoagulation therapy, and liver disease was determined via electronic medical record review. Other conditions that can affect PC, PS, or AT3 levels were recorded if noted. Results Over 5 months, 50 inpatients underwent testing for PC, PS, and/or AT3. Testing was performed within 2 weeks of an acute thrombotic event in 92% of patients; 32% received anticoagulation therapy prior to testing and 16% had liver disease. Test results below the reference range were found in the following percentage of patients: 16% PC, 34% PS, and 16% AT3. In total, 23 of 50 (46%) patients had one or more abnormal results; all 23 had potential confounding conditions/drug. Conclusions Inpatient PC, PS, and AT3 testing was frequently performed in clinical settings, which may cause false-positive or false-negative results. This demonstrates the need for increased education and dialogue between the laboratory and clinicians to improve test utilization practices. Potential interventions are currently being analyzed.

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False Positive and False Negative Radon Measurement Results Due to Uncertainties in Seasonal Correction Factors

Radiation Protection Dosimetry ◽

10.1093/oxfordjournals.rpd.a082473 ◽

1994 ◽

Vol 56 (1-4) ◽

pp. 291-292 ◽

Cited By ~ 8

Author(s):

K.D. Cliff ◽

J.C.H. Miles ◽

S.P. Naismith

Keyword(s):

False Positive ◽

False Negative ◽

Geometric Standard Deviation ◽

Correction Factors ◽

Radon Measurement ◽

Negative Results ◽

False Negative Results ◽

Initial Survey ◽

The Uk ◽

Radon Measurements

Abstract Data from the UK national survey of radon in 2300 homes has been re-analysed to determine the uncertainty in seasonal correction factors applied to measurements of less than l year. The required correction factor for each six-month result was calculated from the known annual average for the appropriate home. The seasonal correction factors derived for each month were found to be approximately log-normally distributed, with an average geometric standard deviation of 1.36. Following this initial survey, radon measurements have been made in more than 80,000 homes in southwest England to determine whether they are above the UK radon Action level of 200 Bq.m-3. The measurements were carried out over three months in each case using etched track detectors in two locations in each home, and the results were corrected for the average seasonal variation found in the original UK study of radon in homes. Because of the uncertainty in the seasonal correction factors, households with between 130 and 300 Bq.m-3 were advised to have a second three-month measurement in a different season before deciding whether or not to take remedial action. More than 7000 homes were remonitored for this purpose. The results are analysed to show the number of false positive and false negative results that would have been reported if advice had been based solely on the initial measurement. It is shown that the present scheme results in extremely small numbers of false positive and false negative results.

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R-177. Incidence of false-positive and false-negative, results from chromosome discrepancies confined to the placenta in 4120 chorionic villus samples

Human Reproduction ◽

10.1093/humrep/12.suppl_2.312 ◽

1997 ◽

Vol 12 (Suppl_2) ◽

pp. 312-312

Author(s):

L. Míguez ◽

C. Fuster ◽

M.M. Perez ◽

M.L. Alegre ◽

M. Sostoa ◽

...

Keyword(s):

False Positive ◽

False Negative ◽

Chorionic Villus ◽

Negative Results ◽

False Negative Results

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Pearls and Pitfalls of Interpretation in CT Colonography

Canadian Association of Radiologists Journal ◽

10.1177/0846537119892881 ◽

2020 ◽

Vol 71 (2) ◽

pp. 140-148

Author(s):

Michael Schonberger ◽

Philippe Lefere ◽

Abraham H. Dachman

Keyword(s):

Computed Tomography ◽

Sensitivity And Specificity ◽

False Positive ◽

Ct Colonography ◽

False Negative ◽

High Sensitivity ◽

Negative Results ◽

False Negative Results ◽

The Common

The accuracy of computed tomography (CT) colonography (CTC) requires that the radiologist be well trained in the recognition of pitfalls of interpretation. In order to achieve a high sensitivity and specificity, the interpreting radiologist must be well versed in the causes of both false-positive and false-negative results. In this article, we review the common and uncommon pitfalls of interpretation in CTC.

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