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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 57, Issue 8


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

Rasmus Søgaard HansenORCID iD: https://orcid.org/0000-0002-5588-5489 / Mads Nybo
  • Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2019-03-23 | DOI: https://doi.org/10.1515/cclm-2018-1382



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.


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


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).


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


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About the article

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

Received: 2018-12-28

Accepted: 2019-02-22

Published Online: 2019-03-23

Published in Print: 2019-07-26

Author contributions: All the authors have 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.

Conflict of interest: None declared.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 57, Issue 8, Pages 1229–1234, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2018-1382.

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