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 procoagulant PLs by histones released during cell injury/death may interfere with coagulation and may serve a local regulatory anticoagulant function. Histone H1 prolonged the PT and APTT of normal pooled plasma (NPP). These increased clotting times disappeared when anti-H1 monoclonal antibody (mAb) was added to the incubation. Dilute Russell Viper Venom Time was also prolonged with the addition of histone H1. When H1 was added to plasma from a patient with the antiphospholipid syndrome (APL plasma), there was a further prolongation of the abnormal APL clotting time which was partially corrected by anti-H1 mAb. Platelet neutralization times were increased with added H1 and were further increased using APL plasma. when disrupted endothelial cells were incubated with plasma with and without anti-H1 antibodies, the addition of anti-H1 antibodies decreased clotting times. These data support the theory that histones released during cell injury may have a regulatory anticoagulant role in clot formation and the anti-H1 effect of some APL plasmas may inhibit this, thereby contributing to thrombosis seen in APL patients.
Kheiri
S A
SA
Long Island Jewish Medical Center Campus, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
Fasy
T M
TM
Billett
H H
HH
D000911:Antibodies, Monoclonal / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000097:blood*; D001323:Autoantibodies / Q000276:immunology*; D001777:Blood Coagulation; D002478:Cells, Cultured; D006657:Histones / Q000276:immunology*; D006801:Humans; D010314:Partial Thromboplastin Time; D011485:Protein Binding; D011517:Prothrombin Time
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D006657:Histones