Danger of false negative (exclusion) or false positive (diagnosis) for ‘congenital thrombophilia’ in the age of anticoagulants
-
Emmanuel J. Favaloro
Abstract
Background
Most guidelines and experts recommend against performance of thrombophilia testing in general, and specifically against testing patients on pharmacological anticoagulants, due to substantially increased risk of false positive identification. For example, vitamin K antagonist (VKA) therapy affects protein C (PC) and protein S (PS), as well as some clotting assays (e.g. as used to investigate activated PC resistance [APCR]). Although heparin may also affect clotting assays, most commercial methods contain neutralisers to make them ‘insensitive’ to therapeutic levels. Direct oral anticoagulants (DOACs) also affect a wide variety of thrombophilia assays, although most reported data has employed artificial in vitro spiked samples.
Methods
In the current report, data from our facility for the past 2.5 years has been assessed for all ‘congenital thrombophilia’ related tests, as evaluated against patient anticoagulant status. We processed 10,571 ‘thrombophilia’ related test requests, including antithrombin (AT; n=3470), PC (n=3569), PS (n=3585), APCR (n=2359), factor V Leiden (FVL; n=2659), and prothrombin gene mutation (PGM; n=2103).
Results
As expected, VKA therapy affected PC and PS, and despite manufacturer claims, also APCR. Most assays, as suggested by manufacturers, were largely resistant to heparin therapy. DOACs’ use was associated with falsely low APCR ratios (i.e. FVL-like effect) and somewhat unexpectedly, anti-Xa agents apixaban and rivaroxaban were also associated with lower AT and higher PS values.
Conclusions
It is concluded that ex-vivo data appears to confirm the potential for both false positive and false negative ‘thrombophilia’ events in patients on anticoagulant (including DOAC) treatment.
Acknowledgments
The author thanks the PathNet Application Specialists (PAS) Team, especially Violeta Ule Priebbenow, Igor Melnikov and Natasha Biktemirova for arranging the data extraction from our laboratory information system (LIS). Various staff from the author’s laboratory are thanked for the performance of the laboratory assays as reported here but as performed as part of their standard duties. New South Wales (NSW) Health Pathology is acknowledged for providing in-kind support to permit study completion. The views expressed in this paper are those of the author and are not necessarily those of NSW Health Pathology.
Author contributions: The author has accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Obituary
- Professor Howard A. Morris
- Editorial
- The silk road to total quality in Laboratory Medicine
- Reviews
- Moving average quality control: principles, practical application and future perspectives
- Serum α-fetoprotein in pediatric oncology: not a children’s tale
- Mini Review
- Value-based healthcare: the role of laboratory medicine
- Opinion Paper
- Advantages and limitations of total laboratory automation: a personal overview
- General Clinical Chemistry and Laboratory Medicine
- Analysis and evaluation of the external quality assessment results of quality indicators in laboratory medicine all over China from 2015 to 2018
- A pilot study for establishing quality indicators in molecular diagnostics according to the IFCC WG-LEPS initiative: preliminary findings in China
- Quality assessment of interpretative commenting and competency comparison of comment providers in China
- Lower creatinine concentration values and lower inter-laboratory variation among Swedish hospital laboratories in 2014 compared to 1996: results from the Equalis external quality assessment program
- Development of the Point-of-Care Key Evidence Tool (POCKET): a checklist for multi-dimensional evidence generation in point-of-care tests
- Analytical and clinical performance evaluation of two POC tests for therapeutic drug monitoring of infliximab
- Hematology and Coagulation
- Provisional standardization of hepcidin assays: creating a traceability chain with a primary reference material, candidate reference method and a commutable secondary reference material
- Danger of false negative (exclusion) or false positive (diagnosis) for ‘congenital thrombophilia’ in the age of anticoagulants
- Point-of-care haemostasis monitoring during liver transplantation is cost effective
- Reference Values and Biological Variations
- Evaluation of reference intervals of haematological and biochemical markers in an Austrian adolescent study cohort
- Cancer Diagnostics
- A novel machine learning-derived decision tree including uPA/PAI-1 for breast cancer care
- Cardiovascular Diseases
- Evaluation of analytical performances using standardized analytical protocols and comparison of clinical results of the new ADVIA BNP and NT-proBNP immunoassays for the Centaur XPT platform
- Infectious Diseases
- Improvement in detecting sepsis using leukocyte cell population data (CPD)
- Letters to the Editor
- The biological variation of plasma proenkephalin: data from a stable heart failure cohort
- Hemoglobin variants found in relation to HbA1c testing: high occurrence of Hb Athens-Georgia in the Northern Jutland, Denmark
- Eltrombopag interferes with the measurement of plasma total bilirubin in pediatric patients in an automated colorimetric method
- A challenging case: highly variable TSH in a mother and her two children
- Suppressing all test results in grossly hemolyzed samples: is this approach appropriate in every case?
- Prozone effect observed for heavy chain α in the serum immunofixation electrophoresis of a patient with monoclonal IgA-λ gammopathy
- Significant allelic dropout phenomenon of Oncomine BRCA Research Assay on Ion Torrent S5
- Evaluation of immature platelet fraction in patients with myelodysplastic syndromes. Association with poor prognosis factors
- Influence of temperature of transport of whole blood on plasma Cu, I, Mn, Se and Zn and Mg concentrations in erythrocytes
- Absorbent materials to collect urine can affect proteomics and metabolomic biomarker concentrations
Articles in the same Issue
- Frontmatter
- Obituary
- Professor Howard A. Morris
- Editorial
- The silk road to total quality in Laboratory Medicine
- Reviews
- Moving average quality control: principles, practical application and future perspectives
- Serum α-fetoprotein in pediatric oncology: not a children’s tale
- Mini Review
- Value-based healthcare: the role of laboratory medicine
- Opinion Paper
- Advantages and limitations of total laboratory automation: a personal overview
- General Clinical Chemistry and Laboratory Medicine
- Analysis and evaluation of the external quality assessment results of quality indicators in laboratory medicine all over China from 2015 to 2018
- A pilot study for establishing quality indicators in molecular diagnostics according to the IFCC WG-LEPS initiative: preliminary findings in China
- Quality assessment of interpretative commenting and competency comparison of comment providers in China
- Lower creatinine concentration values and lower inter-laboratory variation among Swedish hospital laboratories in 2014 compared to 1996: results from the Equalis external quality assessment program
- Development of the Point-of-Care Key Evidence Tool (POCKET): a checklist for multi-dimensional evidence generation in point-of-care tests
- Analytical and clinical performance evaluation of two POC tests for therapeutic drug monitoring of infliximab
- Hematology and Coagulation
- Provisional standardization of hepcidin assays: creating a traceability chain with a primary reference material, candidate reference method and a commutable secondary reference material
- Danger of false negative (exclusion) or false positive (diagnosis) for ‘congenital thrombophilia’ in the age of anticoagulants
- Point-of-care haemostasis monitoring during liver transplantation is cost effective
- Reference Values and Biological Variations
- Evaluation of reference intervals of haematological and biochemical markers in an Austrian adolescent study cohort
- Cancer Diagnostics
- A novel machine learning-derived decision tree including uPA/PAI-1 for breast cancer care
- Cardiovascular Diseases
- Evaluation of analytical performances using standardized analytical protocols and comparison of clinical results of the new ADVIA BNP and NT-proBNP immunoassays for the Centaur XPT platform
- Infectious Diseases
- Improvement in detecting sepsis using leukocyte cell population data (CPD)
- Letters to the Editor
- The biological variation of plasma proenkephalin: data from a stable heart failure cohort
- Hemoglobin variants found in relation to HbA1c testing: high occurrence of Hb Athens-Georgia in the Northern Jutland, Denmark
- Eltrombopag interferes with the measurement of plasma total bilirubin in pediatric patients in an automated colorimetric method
- A challenging case: highly variable TSH in a mother and her two children
- Suppressing all test results in grossly hemolyzed samples: is this approach appropriate in every case?
- Prozone effect observed for heavy chain α in the serum immunofixation electrophoresis of a patient with monoclonal IgA-λ gammopathy
- Significant allelic dropout phenomenon of Oncomine BRCA Research Assay on Ion Torrent S5
- Evaluation of immature platelet fraction in patients with myelodysplastic syndromes. Association with poor prognosis factors
- Influence of temperature of transport of whole blood on plasma Cu, I, Mn, Se and Zn and Mg concentrations in erythrocytes
- Absorbent materials to collect urine can affect proteomics and metabolomic biomarker concentrations
