Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Michaelis, S.
Evaluation of two functional APC resistance assays in comparison with the genetic test method
[ Diplomarbeit ] Medical University of Graz; 2013. pp. 56
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Mangge Harald
- Prüller Florian
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- Abstract:
- Introduction: APC resistance is a laboratory phenotype characterized by poor anticoagulant response to activated protein C (APC). The vast majority of cases is caused by the factor V Leiden (FVLEIDEN) mutation leading to a substitution of arginine to glutamine at position 506 of the factor V molecule. Thus, an APC cleavage site is eliminated and inactivation of activated factor V is altered. Among Caucasians, APC resistance is the most common cause of familial thrombophilia, a genetically based disposition to venous thromboembolism. The thrombotic risk is increased about 2- to 8-fold for heterozygous FVLEIDEN carriers, and 20- to 80-fold for homozygotes. Hence, testing for APC resistance and FVLEIDEN, respectively, is of great clinical importance. The gold standards in testing are PCR methods directly determining the mutation. Due to their high expenses and long turnaround times, more cost-effective and easy applicable functional assays are sought to be implemented in the clinical routine. The aim of this study is the evaluation of the diagnostic usability of two commercially available functional APC resistance assays in comparison to the genetic test method. Materials and Methods: Data from 3086 patients, who underwent thrombophilia screening, was statistically analyzed. All patients had been tested genetically, and either with a functional APTT-based test (2nd generation test), a functional PT-based test (3rd generation test), or both. The cut-off limits, descriptive statistical values and diagnostic values (sensitivity, specificity, positive predictive value, negative predictive value) were calculated. Results: The 3rd generation assay showed great sensitivity and specificity in dis-criminating between wild-type factor V individuals and heterozygotes in FVLEIDEN (0.997 and 1.0, respectively) and between heterozygotes and homozygotes (1.0 and 0.994, respectively). The cut-off levels were clear with considerable gaps. The 2nd generation assay showed lower discriminatory efficiency with sensitivity and specificity between wild-types and heterozygotes of 0.973 and 0.989, respectively. Discussion: The 3rd generation test is appropriate as a screening test for APC resistance helping to reduce the necessity of genetic testing. Misclassified samples were predominantly attributable to additional mutations on the factor V gene.