ABSTRACT
We describe here results from the United Kingdom National External Quality Assessment
Scheme (UK NEQAS) Thrombophilia Screening Program, in which an average of 21% of 280
centers reported an incorrect diagnosis for a series of plasma samples. Three case
studies are described, showing causes of error in individual laboratories, related
to the source of reference plasma or reagents. Methodological bias is also described.
For protein C (PC) assays 18% of centers reported PC deficiency in a patient homozygous
for factor V Leiden. Studies in the NEQAS laboratory confirmed the effect of activated
protein C resistance (APCR) on clot-based PC activity assays. Differences in results
obtained for PS-deficient subjects with different protein S (PS) activity kits are
reported; several subjects would be misdiagnosed as normal with one kit if the manufacturer's
reported reference range was adopted instead of a locally determined reference range.
Antithrombin (AT) assays were shown to vary in their sensitivity to different molecular
defects in the antithrombin gene; 77% of centers employing human thrombin-based activity
assays reported a normal AT level in a patient with antithrombin Cambridge II. Sensitivity
of the APC resistance test in the absence of factor V-deficient plasma was shown to
be improved through normalization of results, and errors in the genetic diagnosis
of factor V Leiden and the P20210A prothrombin gene mutation are described. Errors
in the diagnosis of thrombophilic defects can therefore be identified through participation
in EQA programs, and following dissemination of information, improvements in diagnosis
can be demonstrated.
KEYWORDS
Quality assurance testing - antithrombin - protein C - protein S - activated protein
C resistance - factor V Leiden - prothrombin gene mutation
REFERENCES
ian@coageqa.org.uk
