Effect of anti-beta2glycoprotein I Lupus Anticoagulants on fibrin polymerization and fibrinolysis.
Anti-beta2-Glycoprotein I (beta2GPI) autoantibodies are the prominent laboratory feature of Hughes syndrome. By prolonging some coagulation tests in the presence of exogenous phospholipids (PL), they behave as classical Lupus Anticoagulants (LA). We investigated the effect of 3 affinity-purified anti-beta2GPI IgG preparations from patients with Hughes syndrome on fibrin polymerization and fibrinolysis of normal plasma, measured by comparing the optical densities of assay mixtures in the presence of the autoantibodies or normal IgG. The presence of anti-beta2GPI IgG in diluted Russell Viper Venom Time (dRVVT) assays, carried out using a PL dilution of 1:8 or 1:64, resulted in a delay in the onset of polymerization by 30-40 and 60-70s, respectively. Fibrin polymerization was complete after 250s for both anti-beta2GPI IgG and normal IgG. The inhibitory effect of the anti-beta2GPI antibodies was not observed in the presence of excess PL, as expected for LA. Anti-beta2GPI IgG increased the plateau level of polymerization when dRVVT was performed in the presence of 1.5 nM recombinant tissue plasminogen activator, but did not impair the fibrinolytic process, which was almost complete after 250 min. The autoantibodies did not delay the onset of fibrin polymerization in tests carried out using recombinant tissue factor. On the contrary, the autoantibodies enhanced polymerization in prothrombin time assays, and accelerated it in tissue thromboplastin inhibition tests, with no effect on fibrinolysis. These data provide evidence that anti-beta2GPI LA may act as either anticoagulants or procoagulants in different in vitro coagulation tests.
Pengo
V
V
Department of Clinical and Experimental Medicine, Thrombosis Center, University of Padova School of Medicine, Ex Busonera Hospital, Italy. pengo@ux1.unipd.it
Biasiolo
A
A
Brocco
T
T
Rampazzo
P
P
D000293:Adolescent; D000328:Adult; D001704:Biopolymers; D001777:Blood Coagulation; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification; D016682:Lupus Coagulation Inhibitor / Q000302:isolation & purification / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000037:antagonists & inhibitors; D053482:beta 2-Glycoprotein I
D001704:Biopolymers; D006023:Glycoproteins; D007074:Immunoglobulin G; D016682:Lupus Coagulation Inhibitor; D053482:beta 2-Glycoprotein I; D005337:Fibrin; D013917:Thrombin