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The association between activated protein C ratio and Factor V Leiden are gender-dependent

  • Rasmus Søgaard Hansen ORCID logo EMAIL logo and Mads Nybo
Published/Copyright: March 23, 2019
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 57 Issue 8

Abstract

Background

The most common cause of activated protein C (aPC) resistance is a missense substitution (Arg506Gln), known as Factor V Leiden (FVL). Due to its low cost, many laboratories use the aPC ratio as a primary test with a unisex cut-off. However, the association between the aPC ratio and FVL including any relation to gender has been sparsely investigated.

Methods

Results of the aPC ratio and FVL analyses from 1081 patients referred to the Thrombophilia Clinic at Odense University Hospital were compared.

Results

In 153 FVL positive patients, the mean aPC ratio was 2.1 ± 0.3, which differed from 2.7 ± 0.4 in FVL negative individuals (p < 0.01). The receiver operating characteristics (ROC), with area under the curve (AUC) of 0.93, indicated the optimal aPC cut-off at 2.3–2.4, with sensitivity 89%–94%, specificity 71%–84%, positive predictive value 35%–48% and negative predictive value 98%–99%. In FVL positive females, the mean aPC ratio was 2.0 ± 0.3, which differed from males (2.1 ± 0.3, p < 0.05). In FVL negative females, the mean aPC ratio was 2.6 ± 0.4, also different from males (2.8 ± 0.5, p < 0.01). Of note, 35% of FVL negative females had an aPC ratio ≤2.4 against 18% in males (p < 0.01).

Conclusions

Our results indicate that the aPC ratio is lower in females than in males. Due to a high negative predictive value the aPC ratio can be used as a first line test for FVL, but those found positive must be confirmed with a DNA test.

Keywords: activated protein C; Arg506Gln; Factor V Leiden; gender
Corresponding author: Rasmus Søgaard Hansen, MD, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark, Phone: +45 2886 2288

Acknowledgments

All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

  6. Conflict of interest: None declared.

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Received: 2018-12-28
Accepted: 2019-02-22
Published Online: 2019-03-23
Published in Print: 2019-07-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2018-1382
Keywords for this article
activated protein C; Arg506Gln; Factor V Leiden; gender

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. CCLM Award for the Most Cited Paper
  4. Folate and vitamin B12 assays after recalibration to the WHO International Standard 03/178: making the interpretation as simple as possible, but not simpler
  5. Reviews
  6. Blood contamination in salivary diagnostics: current methods and their limitations
  7. Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment
  8. Genetics and Molecular Diagnostics
  9. Measuring the chronology of the translational process of molecular genetic discoveries
  10. Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements
  11. General Clinical Chemistry and Laboratory Medicine
  12. Post-translational modification-derived products are associated with frailty status in elderly subjects
  13. Urine chloride self-measurement to monitor sodium chloride intake in patients with chronic kidney disease
  14. Estimated urinary osmolality based on combined urinalysis parameters: a critical evaluation
  15. Measurement of S100B protein: evaluation of a new prototype on a bioMérieux Vidas® 3 analyzer
  16. Measuring thyroglobulin in patients with thyroglobulin autoantibodies: evaluation of the clinical impact of BRAHMS Kryptor® Tg-minirecovery test in a large series of patients with differentiated thyroid carcinoma
  17. Human chorionic gonadotropin suspected heterophile interference investigations in immunoassays: a recommended approach
  18. Certified reference material against PR3 ANCA IgG autoantibodies. From development to certification
  19. Diagnostic accuracy of a fully automated multiplex celiac disease antibody panel for serum and plasma
  20. Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status
  21. Hematology and Coagulation
  22. The association between activated protein C ratio and Factor V Leiden are gender-dependent
  23. Reference Values and Biological Variations
  24. Determination of sigma score based on biological variation for haemostasis assays: fit-for-purpose for daily practice?
  25. Calcitonin measurement in pediatrics: reference ranges are gender-dependent, validation in medullary thyroid cancer and thyroid diseases
  26. Cancer Diagnostics
  27. Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence
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  29. Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients – evidence for sex-specific differences
  30. Infectious Diseases
  31. Rapid susceptibility testing of multi-drug resistant Escherichia coli and Klebsiella by glucose metabolization monitoring
  32. Letters to the Editor
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  34. Reference values of a new serum folate assay traceable to the WHO International Standard
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