Complexes of anti-prothrombin antibodies and prothrombin cause lupus anticoagulant activity by competing with the binding of clotting factors for catalytic phospholipid surfaces

We investigated the mechanism by which antiprothrombin antibodies cause lup us anticoagulant (LAC) activity. Addition of affinity-purified anti-prothro mbin antibodies from LAG-positive plasma samples (alpha -FII-LAC(+)) to nor mal plasma induced LAC activity, Upon increasing the phospholipid concentra tion, LAC activity was neutralized, Addition of purified alpha -FII-LAC(+) to normal plasma strongly inhibited factor Xa formation, No inhibition was measured when alpha -FII-LAC(+) were added to prothrombin-deficient plasma or when purified anti-prothrombin antibodies from LAC-negative plasma sampl es (alpha -FII-LAC(-)) were added. When a combination of prothrombin and al pha -FII-LAC(+) was added to the purified clotting complex, a strong inhibi tion of factor Xa and IIa formation was seen, The alpha -FII-LAC(+) alone o r a combination of prothrombin and alpha -FII-LAC(-) did not show inhibitio n. Ellipsometry studies showed that, in the presence of alpha -FII-LAC(+), the affinity of prothrombin for a phospholipid surface increased dramatical ly, whereas a much lower increase was observed with alpha -Fn-LAC(-). Our r esults show that complexes of prothrombin and antiprothrombin antibodies wi th LAC activity inhibit both prothrombinase and tenase, The antibodies incr ease the affinity of prothrombin for the phospholipid surface, thereby comp eting with clotting factors for the available catalytic phospholipid surfac e, a mechanism similar to that of anti-beta (2)-glycoprotein I antibodies.