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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3300-3302
BRIEF REPORT
Induction of monocyte tissue factor expression by antibodies to
heparin-platelet factor 4 complexes developed in heparin-induced
thrombocytopenia
Claire Pouplard,
Sophie Iochmann,
Benoit Renard,
Olivier Herault,
Philippe Colombat,
Jean Amiral, and
Yves Gruel
From the Departments of Hematology and Hemostasis
and Hematology/Oncology, Faculté de Médecine, Tours, and
Hyphen Biomed, Andresy, France.
The pathogenesis of thrombosis in heparin-induced thrombocytopenia
(HIT) was studied by investigating whether antibodies to heparin-platelet factor 4 (H-PF4) induced tissue factor (TF) synthesis by monocytes. Plasma from 5 patients with HIT containing IgG to H-PF4
was incubated with peripheral blood mononuclear cells without or with
purified PF4 and heparin. Significant TF-dependent procoagulant activity (PCA) expressed by monocytes, measured with a factor Xa-based
chromogenic assay, was induced after incubation of each HIT plasma
sample. This monocyte PCA required the presence of PF4 and was
inhibited by high concentrations of heparin. Furthermore, purified HIT
IgG added to whole blood with PF4 and heparin also provoked significant
synthesis of TF mRNA by monocytes, demonstrated by RT-PCR, and this
effect was not observed with normal IgG. These findings strongly
support the hypothesis that antibodies to PF4 developed in HIT trigger
the production of tissue factor by monocytes, and this effect could
account in vivo for hypercoagulability and thrombotic complications in
affected patients.
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