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Blood, 15 August 2001, Vol. 98, No. 4, pp. 1252-1254
BRIEF REPORT
Antibodies from patients with heparin-induced thrombocytopenia
stimulate monocytic cells to express tissue factor and secrete
interleukin-8
Gowthami M. Arepally and
Irene M. Mayer
From the Cancer Research and Treatment Center and
Department of Medicine, the University of New Mexico Health Sciences
Center, Albuquerque, NM.
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.
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