Cross Reactivity Using Activation Assays

Cross-reactivity studies have been performed most frequently using activation assays. However, there are no standard methods for, or even a standard definition of, in vitro cross-reactivity. In one study of LMWH and danaparoid cross-reactivity, an increase in platelet activation in the presence of the drug over baseline was used to determine cross-reactivity (Warkentin, 1996). This definition was used to avoid falsely attributing cross-reactivity to drug-independent platelet activation that is produced by some patients' sera. The reason for this definition was the common phenomenon that platelet activation can be caused by a patient's serum even in the absence of added heparin. In the HIPA test, comparison of the lag time to aggregation can be used to judge cross-reactivity: if a sample shows platelet aggregation with danaparoid or LMWH earlier than in the presence of buffer, then cross-reactivity is present. In general, in vitro cross-reactivity with danaparoid is usually clinically insignificant (Warkentin, 1996; Newman et al., 1998) (see Chapters 12 and 13).

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