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Heparin employed in extracorporeal circuits often leads to hemorrhagic complications. Protamine employed for heparin neutralization can cause adverse hemodynamic responses. To control both types of complications, the authors propose an approach that consists of placing a filter device containing immobilized protamine (defined as a protamine filter) at the termination of the extracorporeal blood circulation (ECBC) procedure. This protamine filter would remove heparin from the extracorporeal circuit before heparin is returned to the patient. Meanwhile, the filter would also permit external protamine treatment. Since protamine toxicity generally results from the interaction of protamine with certain cells present in the liver, lungs, and tissues, the use of external protamine would minimize its potential adverse effects. Protamine was immobilized on a hollow fiber bundle obtained from a conventional hemodialyzer. Preliminary studies show that the protamine bound bundle is capable of neutralizing the anticoagulant activity of heparin both in vitro and in vivo. In addition, the protamine filter has abolished the hypotensive response normally associated with protamine reversal of heparin, as indicated by the insignificant changes in blood pressure, pulse rate, pulmonary artery systolic/diastolic pressures, and cardiac output. Further in vivo studies involving the use of dogs, as well as investigation of the activation of the complement system by the protamine filter, are currently being conducted.