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 pa tients with heparin-induced thrombocytopenia (HITT). The pathogenic mechani sms underlying the variable occurrence of thrombosis in HITT is poorly unde rstood. it was hypothesized that monocyte activation leading to tissue fact or expression may play a role in promoting a thrombogenic state in HITT. Th is study demonstrates that a human platelet factor 4 (PF4)/heparin-specific murine monoclonal antibody (KKO) binds to peripheral blood-derived human m onocytes in a PF4-dependent manner. KKO and antibodies from patients with H ITT induce monocytes to synthesize and secrete interleukin-8 and induce cel l-surface procoagulant activity, which is abrogated following treatment wit h antihuman tissue factor antibody. The findings suggest a novel mechanism by which PF4/heparin antibodies may promote a hypercoagulable, state in pat ients with HITT.