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Impaired catalytic function of activated protein C: a new in vitro
manifestation of lupus anticoagulant
E Marciniak and EH Romond
Department of Medicine, University of Kentucky Medical Center, Lexington
40536.
Lupus anticoagulant (LA), an antibody against anionic phospholipid with
anticoagulant laboratory manifestations, is paradoxically associated with a
high incidence of thrombosis. In the present study we analyzed the
phospholipid- and platelet-dependent degradation of factor Va following
clotting in plasma from 15 consecutive patients with LA to provide evidence
for a distinct procoagulant effect of the antibody. After clotting with 25
micrograms phospholipid/mL, all samples containing LA showed markedly
decreased rates of factor Va degradation (k = 0.01 to 0.14 min-1 v 0.27 to
0.35 min-1 in controls). Also with higher phospholipid concentrations (up
to 100 micrograms/mL), as well as in the presence of platelets (5 to 33 x
10(7)/mL), significantly less of the procoagulant activity disappeared per
unit of time in samples with LA than in controls. Plasma with LA was to a
variable extent capable of decreasing or abolishing factor Va inhibition in
normal plasma. Most importantly, exogenous activated protein C failed to
correct the ineffective factor Va destruction despite adequate protein S
levels. These data suggest that LA prevents the formation of the complex
essential for rapid proteolysis of factor Va both on phospholipid and on
the platelet membrane, thereby compromising the catalytic function of
activated protein C. Our findings offer a new opportunity for a more
comprehensive evaluation of patients with antiphospholipid antibody in
defining the pathogenesis of thrombosis in this clinical condition.
Volume 74,
Issue 7,
pp. 2426-2432,
11/15/1989
Copyright © 1989 by The American Society of Hematology
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