Immune thrombocytopenia following injection of anti-hPF4/heparin antibody and heparin.

(A) Mice transgenic for both FcγRIIA and hPF4 (▪, ■), transgenic for FcγRIIA only (♦, ⋄), and transgenic for hPF4 only (▴, ▵) were injected with 400 μg antibody IP followed by daily subcutaneous injections of heparin (20 U per mouse). Platelet counts, obtained at the time points indicated, are shown as a percentage of baseline values for transgenic mice treated with anti-hPF4/heparin (▪, ♦, ▴) or isotype control (■, ⋄, ▵) antibodies. Only the transgenic FcγRIIA/hPF4 mice injected with anti-hPF4/heparin antibody and heparin developed severe thrombocytopenia, as shown by an 80% drop in the platelet count. (B) Nadir platelet counts following antibody and heparin injections. The graph shows the mean nadir platelet counts as the percentage ± one SD of baseline for mice transgenic for both FcγRIIA and hPF4 (▪), transgenic for FcγRIIA only (▨), and transgenic for hPF4 only (■) treated with anti-hPF4/heparin or isotype control antibodies prior to heparin injections. The nadir for the double-transgenic mice treated with anti-hPF4/heparin antibody and heparin was 78.6% ± 10.8% below baseline platelet counts, which was significantly different from the control subjects (*P < .001, ANOVA). The nadir counts for the transgenic lines treated with isotype control antibody were not significantly different.