Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3814-3819
Procoagulant Effect of Anti-
2-Glycoprotein I Antibodies With Lupus
Anticoagulant Activity
V. Pengo,
T. Brocco,
A. Biasiolo,
P. Rampazzo,
P. Carraro, and
R. Zamarchi
From the Department of Clinical and Experimental
Medicine, Thrombosis Center, the Department of
Laboratory Medicine, and the Department of Oncology and
Surgical Sciences, University of Padova School of
Medicine, Padova, Italy.
Prothrombin time (PT) is routinely used to monitor oral
anticoagulant treatment in patients with the antiphospholipid antibody syndrome (APS). The fact that PT is a phospholipid (PL)-dependent coagulation test raises the possibility that lupus anticoagulant (LA)
might interfere with this test, thus complicating the control of
anticoagulant treatment. The effect of 6 affinity-purified preparations
of anti- (a)
2-glycoprotein I (GPI) antibodies with LA
activity on the PT was tested. Instead of prolonging PT as expected,
the a
2-GPI antibodies reduced the PT of both normal plasma and
anticoagulated plasma by a mean of 2.4 seconds and 5.6 seconds,
respectively. This effect was also observed using other 5 commercially
available preparations of thromboplastin. The a
2-GPI-mediated
reduction in PT was dose-dependent and was lost upon removal of
2-GPI. The failure of a
2-GPI antibodies to express LA activity in
PT was found to depend on the fact that calcium ions were added
together with PL at the beginning of the assay. In fact, modification
of the standard diluted Russell viper venom time (dRVVT) test by adding
calcium ions together with PL resulted in a loss of a
2-GPI
anticoagulant activity. The procoagulant effect was not as evident in
an assay that used stimulated monocytes as a source of thromboplastin.
These results show that a
2-GPI antibodies exhibit an `in vitro'
procoagulant effect in PT and an anticoagulant effect in dRVVT only
when the interaction with their antigen and PL occurs in the absence of
calcium ions.