Anti-prothrombin antibodies and the lupus anticoagulant

Abstract

The investigators have evaluated the frequency and manifestations of anti-prothrombin antibodies in patients with the lupus anticoagulant. Thirty-one of 42 patients with lupus anticoagulants associated with a variety of underlying conditions (74%) had evidence on crossed immunoelectrophoresis of anti-prothrombin antibodies. Twenty-four of 25 patients with an activated partial thromboplastin time exceeding 50 seconds and 14 of 15 patients with a prothrombin time exceeding control by more than two seconds had demonstrable anti-prothrombin antibodies. Three of the 31 patients with anti-prothrombin antibodies had essentially no measurable plasma prothrombin, a presumed result of accelerated clearance of prothrombin/prothrombin antibody complexes. Each of these patients had bled abnormally. The remaining patients with anti-prothrombin antibodies had neither substantial hypoprothrombinemia nor hemorrhagic manifestations, which confirms the non-neutralizing property of anti-prothrombin antibodies associated with the lupus anticoagulant. Since lupus anticoagulant immunoglobulins are known to react with phospholipids, the high prevalence of antibodies binding prothrombin led us to test the hypothesis of antibody polyreactivity. Adsorption of three lupus anticoagulant plasmas with insolubilized prothrombin markedly diminished evidence of both prothrombin/prothrombin antibody complexes and anticoagulant activity. Eluates of the insolubilized prothrombin contained IgG that not only bound prothrombin but possessed lupus anticoagulant activity.