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The use of pazopanib was associated with a significantly increased risk of severe non-fatal hepatotoxicity in cancer patients.

Background Protamine is widely used to reverse the anticoagulant effects of heparin. Although mild thrombocytopenia is common in patients given protamine after cardiac procedures, acute severe thrombocytopenia has not been described. We encountered a patient who experienced profound thrombocytopenia and bleeding shortly after administration of protamine and performed studies to characterize the responsible mechanism. Study design and methods Patient serum was studied for antibodies that recognize protamine, heparin/protamine complexes and platelets pre-treated with protamine using flow cytometry, ELISA and serotonin release from labeled platelets. Results A high titer IgG antibody was detected in patient serum that recognizes protamine in a complex with heparin or platelet surface glycosaminoglycans (GAG) and activates platelets pre-treated with protamine at concentrations achieved in vivo following protamine infusion. The antibody is distinctly different from those found in patients with heparin-induced thrombocytopenia on the basis of its failure to recognize heparin in a complex with platelet factor 4 (PF4) and to release serotonin from labeled platelets in the absence of protamine. Conclusions Findings made suggest that the patient’s antibody is specific for conformational changes induced in protamine when it reacts with heparin or a platelet surface GAG. Development of severe thrombocytopenia following treatment of this patient with protamine defines a previously undescribed mechanism of drug-induced immune thrombocytopenia. Patients given protamine who produce this type of antibody may be at risk to experience thrombocytopenia if given the drug a second time while antibody is still present.