Reduced Reactivity Towards Anti-Protamine Antibodies of a Low Molecular Weight Protamine Analogue

Abstract

Protamine sulfate has been used routinely following cardiovascular surgery to reverse the anticoagulant activity of heparin. This clinical use, however, at times, is associated with adverse effects ranging from mild hypotension to severe, idiosyncratic fatal reactions [1–4]. In general, protamine responses can be distinguished into either via a nonimmunologic pathway or via an immunoglobin-mediated pathway. Adverse reactions produced by the first mechanism are more common and can be largely aborted using conventional pressor agents and slow protamine administration. Anaphylactic-type responses produced by the second pathway (termed “Type I protamine hypersensitivity”), however, are unpredictable, life threatening, and not readily manageable by clinical intervention. More than 100 protamine-related deaths have been reported in the literature that is attributed to this mechanism [1–4]. Owing to this immunopathogenic function of protamine, a large population of diabetic patients is at high risk to acquire severe protamine response following heparin reversal, primarily due to the routine use of protamine zinc insulin (PZI) or neutral protamine Hagedorn (NPH) by such patients. Indeed, several cases of anaphylaxis to protamine masquerading as insulin allergy have been reported to occur in protamine-containing insulin-dependent diabetes [5,6].