Platelet activation and neutrophil activation induced by anti-PF4/heparin ICs are distinct processes. (A) Most functional anti-PF4/heparin antibodies are capable of both platelet and neutrophil activation. Whole blood from a healthy donor was incubated with plasma from individual healthy donors (n = 16), plasma from patients with anti-PF4/heparin antibodies who tested negative in the PEA (n = 11), or with plasma from seropositive patients who were PEA positive (n = 16; all at 1:10 dilution), along with PF4 (25 µg/mL) and heparin (1 U/mL). After 30 minutes of incubation, MMP-9 release was measured in plasma. Data shown are representative of 3 independent experiments. *P < .05; ***P < .0005. Results are expressed as mean ± standard deviation. (B) Platelet activation and neutrophil activation are distinct processes. PEA results in patients with anti-PF4/heparin antibodies (n = 27) are plotted as a function of percent MMP-9 release (Spearman r = 0.42; P = .03). Patients who test positive in the PEA but negative in the MMP-9 assay are shown in red. Patients who test positive in the MMP-9 assay but negative in the PEA are shown in yellow. ns, not significant.