An in vitro phagocytosis method to predict the in vivo potential of integrin antagonists/agonists to induce thrombocytopenia

摘要

This invention relates to the use of an in vitro cell-based phagocytosis method to determine the potential of integrin antagonists or agonists to induce thrombocytopenia. The method measures the extent of phagocytosis in samples containing (i) platelets, (ii) an integrin antagonist or agonist and (iii) a sample known to contain or which may contain integrin antagonist or agonist drug-dependent anti-platelet antibodies. The phagocytosis process in the method is preferably measured using chemiluminescence or dyes. The method is useful for screening integrin antagonists/agonists, such as glycoprotein IIb/IIIa receptor (GPIIb/IIIa) antagonists, for their phagocytotic and therefore thrombocytopenic potential in the presence of drug-dependant antibodies. The present methods are also useful for identifying patients who may be at risk to develop thrombocytopenia mediated by treatment with an integrin antagonist or agonist. This invention is also useful for the identification of new integrin antagonists or agonists which do not mediate the binding of drug-dependent antibodies to platelets and which do not mediate thrombocytopenia.