These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Functional activated protein C resistance assays: correlation with factor V DNA analysis is better with RVVT-than APTT-based assays.
    Author: Favaloro EJ, Mirochnik O, McDonald D.
    Journal: Br J Biomed Sci; 1999; 56(1):23-33. PubMed ID: 10492912.
    Abstract:
    We compare results of factor V DNA analysis with three different clotting-based assays designed to detect activated protein C (APC) resistance (APCR), using samples from 958 patients undergoing assessment for thrombophilia. The original and most commonly used APTT-based procedure (generating an APTT ratio in presence versus absence of APC), showed the least correlation with DNA findings, with a large overlap between normals and heterozygotes. Using this procedure, over 40% of patients with a normal DNA pattern gave APTT ratio results within the heterozygotes' ratio range, and thus is a poor predictor for factor V DNA Leiden mutation (sensitivity 94.3%, specificity 47.0% [APC ratio cut-off: 3.1]; sensitivity 52.1%, specificity 92.9% [APC ratio cut-off: 2.0]). Two commercially available procedures (protein C impedance [PCI] test and protein C pathway [PCP] test), using modified Russell's viper venom time (RVVT) assays, showed less overlap between normals and heterozygotes than did the APTT-based method. Fewer than 10% of normal individuals gave PCI or PCP test ratio results that fell within the respective heterozygotes' ratio range (PCI: sensitivity 95.3%, specificity 96.0%; PCP: sensitivity 97.3%, specificity 82.4% [APC ratio cut-off: 1.6 and 1.9 respectively]). Use of previously described normalisation procedures (patient's APTT ratio over pooled normal plasma [PNP] APTT ratio) showed little improvement in discriminatory power (sensitivity 96.4%, specificity 44.8% [normalised APC ratio cut-off value: 0.97]; sensitivity 58.8%, specificity 90.1% [normalised APC ratio cut-off: 0.68]). Use of factor V-deficient plasma as sample diluent improved discrimination for all assays, but added considerable time and cost to the testing process. Furthermore, use of factor V-deficient plasma dilutions in the APTT-based test (sensitivity 97.1%, specificity 93.8% [APC ratio cut-off: 2.0]) did not substantially improve discrimination compared with either PCI or PCP performed without factor V-deficient plasma. Overall, a combination of RVVT- and APTT-based tests was found to provide excellent discrimination, particularly negative prediction, with respect to the likely factor V DNA result. Of 567 patients co-tested, all factor V DNA-normal patients (n = 299) gave both PCP-RVVT and APCR-APTT (not prediluted with factor V-deficient plasma) test ratio values > or = 2.2. In conclusion, it is important to recognise the limitation of plasma-based assays, in particular the APTT procedure, to discriminate the factor V mutation.
    [Abstract] [Full Text] [Related] [New Search]