An improved algorithm for activated protein C resistance and factor V Leiden screening

Am J Clin Pathol. 2013 Sep;140(3):379-86. doi: 10.1309/AJCPO6VUP3MZEYWU.

Abstract

Objectives: To evaluate the performance of a Russell viper venom-based activated protein C resistance (APCR) screening test relative to DNA analysis for the factor V Leiden mutation.

Methods: We evaluated the concordance between Pefakit APCR screening results and DNA analysis for 435 patients homozygous (n = 11), heterozygous (n = 310), or wild-type (n =114) for the G1691A allele.

Results: Using receiver operating characteristic analysis, we found that a cutoff of 1.89 for the APCR ratio yields a sensitivity and specificity of 99.1%. In patients with discrepant genotype-phenotype correlation, their APCR may provide a more clinically relevant result.

Conclusions: We compared several strategies for employing reflex testing and found that performing initial APCR screening followed by confirmatory molecular analysis on a subset of cases in the borderline regions between the diagnostic groups can reduce unnecessary testing by approximately 80% without compromising diagnostic accuracy.

Keywords: Activated protein C resistance; Factor V Leiden; Screening assays; Venous thromboembolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activated Protein C Resistance / blood
  • Activated Protein C Resistance / diagnosis*
  • Activated Protein C Resistance / genetics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms*
  • Alleles
  • Child
  • Child, Preschool
  • Factor V / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Testing / methods*
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • factor V Leiden
  • Factor V