Use of a generally applicable tissue factor--dependent factor V assay to
detect activated protein C-resistant factor Va in patients receiving
warfarin and in patients with a lupus anticoagulant
DT Le, JH Griffin, JS Greengard, V Mujumdar and SI Rapaport
Department of Medicine, University of California, San Diego, USA.
The original activated partial thromboplastin time-based assay for
activated protein C (APC)-resistant factor Va (FVa) requires carefully
prepared fresh plasma and cannot be used in patients receiving warfarin or
in patients with antiphospholipid antibodies. A new test is described here
that circumvents these limitations and distinguishes without overlap
heterozygotes for APC-resistant FVa from persons with normal FV. A diluted
test plasma is incubated with an FV-deficient substrate plasma and tissue
factor and then clotted with Ca2+ or Ca2+ plus APC. Test results are
independent of the FV level or the dilution of the test plasma used. Of 39
controls, 37 gave normal results. Two controls (5%) gave results indicative
of APC resistant FVa and on DNA analysis were found to be heterozygous for
FV R506Q. Twenty of 21 randomly selected patients receiving warfarin gave
normal results. In the single patient with abnormal results, heterozygous
FV R506Q was confirmed by DNA analysis. Two of 15 patients with protein S
deficiency and 5 of 29 patients with a lupus anticoagulant had abnormal
results. APC resistance caused by FV R506Q was confirmed in the five of
these seven patients available for DNA analysis. APC-resistant FVa was also
detected in 10 of 21 (46%) stored plasma from unrelated patients with
venous thrombosis and negative earlier evaluation for a lupus anticoagulant
or a deficiency of protein C, protein S, or antithrombin, which confirms a
high incidence of this defect among patients with venous thrombosis.
Volume 85,
Issue 7,
pp. 1704-1711,
04/01/1995
Copyright © 1995 by The American Society of Hematology
