EFFECTS OF H1 HISTONES AND A MONOCLONAL AUTOANTIBODY TO H1 HISTONES ON CLOT FORMATION IN-VITRO - POSSIBLE IMPLICATIONS IN THE ANTIPHOSPHOLIPID SYNDROME

Histones are known to bind anionic phospholipids (PLs). Binding of pro coagulant PLs by histones released during cell injury/death may interf ere with coagulation and may serve a local regulatory anticoagulant fu nction. Histone H1 prolonged the PT and APTT of normal pooled plasma ( NPP). These increased clotting times disappeared when anti-H1 monoclon al antibody (mAb) was added to the incubation. Dilute Russell Viper Ve nom Time was also prolonged with the addition of histone H1. When H1 w as added to plasma from a patient with the antiphospholipid syndrome ( APL plasma), there was a further prolongation of the abnormal APL clot ting time which was partially corrected by anti-H1 mAb. Platelet neutr alization times were increased with added H1 and were further increase d using APL plasma. When disrupted endothelial cells were incubated wi th plasma with and without anti-H1 antibodies, the addition of anti-H1 antibodies decreased clotting times. These data support the theory th at histones released during cell injury may have a regulatory anticoag ulant role in clot formation and the anti-H1 effect of some APL plasma s may inhibit this, thereby contributing to thrombosis seen in APL pat ients.