Antibodies from patients with heparin-induced thrombocytopenia stimulate monocytic cells to express tissue factor and secrete interleukin-8.
Thrombosis is a life-threatening complication that occurs in a subset of patients with heparin-induced thrombocytopenia (HITT). The pathogenic mechanisms underlying the variable occurrence of thrombosis in HITT is poorly understood. It was hypothesized that monocyte activation leading to tissue factor expression may play a role in promoting a thrombogenic state in HITT. This study demonstrates that a human platelet factor 4 (PF4)/heparin-specific murine monoclonal antibody (KKO) binds to peripheral blood-derived human monocytes in a PF4-dependent manner. KKO and antibodies from patients with HITT induce monocytes to synthesize and secrete interleukin-8 and induce cell-surface procoagulant activity, which is abrogated following treatment with antihuman tissue factor antibody. The findings suggest a novel mechanism by which PF4/heparin antibodies may promote a hypercoagulable state in patients with HITT. (Blood. 2001;98:1252-1254)
Arepally
G M
GM
Cancer Research and Treatment Center and Department of Medicine, the University of New Mexico Health Sciences Center, Albuquerque, NM, USA. arepally@unm.edu
Mayer
I M
IM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001323:Autoantibodies / Q000494:pharmacology*; D003029:Coagulants / Q000494:pharmacology; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010978:Platelet Factor 4 / Q000494:pharmacology; D013921:Thrombocytopenia / Q000139:chemically induced / Q000150:complications / Q000276:immunology*; D019851:Thrombophilia / Q000139:chemically induced / Q000209:etiology / Q000276:immunology; D013925:Thromboplastin / Q000096:biosynthesis* / Q000187:drug effects / Q000494:pharmacology; D013927:Thrombosis / Q000209:etiology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D003029:Coagulants; D016209:Interleukin-8; D010978:Platelet Factor 4; D006493:Heparin; D013925:Thromboplastin