Activated protein C resistance: a comparison between two clotting assays and their relationship to the presence of the factor V Leiden mutation.
Resistance to the anticoagulant effect of activated protein C (APC resistance), a frequent abnormality in patients with a history of venous thrombosis, is known to be due, in the large majority of cases, to the presence of an abnormal factor V: the factor V Leiden. It is reasonable to surmise that screening for this abnormality should be performed with a clotting method for APC resistance, before submitting the patients with abnormal results to DNA analysis. The present study was performed on 216 individuals enrolled at the Bologna centre, of which 189 were unrelated patients with a history of juvenile venous thromboembolism and 27 were relatives with or without thrombosis. APC resistance was first measured in Bologna by a standard commercial method and then, in Leiden, by an in-house method: DNA analysis was performed in those cases in which at least one of the clotting methods was abnormal. The data obtained confirm the good performance and the optimal positive predictive value for the Leiden mutation (100%) of the Leiden in-house clotting method. Performance of the commercial method was less satisfactory but markedly improved by expressing the data in relation to the values simultaneously obtained with a normal plasma pool. Even with optimal data expression, however, the positive predictive value of the commercial method, versus DNA analysis, did not exceed 88%. It is concluded that further standardization of the commercial method here evaluated is necessary before it can be widely adopted for the screening of APC resistance and prediction of the presence of factor V Leiden.
Legnani
C
C
Department of Angiology and Blood Coagulation, University Hospital S. Orsola, Bologna, Italy.
Palareti
G
G
Biagi
R
R
Coccheri
S
S
Bernardi
F
F
Rosendaal
F R
FR
Reitsma
P H
PH
de Ronde
H
H
Bertina
R M
RM
D001780:Blood Coagulation Tests; D001796:Blood Protein Disorders / Q000235:genetics / Q000378:metabolism*; D005165:Factor V / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D011486:Protein C / Q000378:metabolism*
D011486:Protein C; D005165:Factor V