A System for Heparin Removal

Abstract

Extracorporeal medical machines rely on systemic heparinization to improve blood compatibility. However, heparin can lead to serious complications such as hemorrhaging. We propose a new approach to control heparin levels by employing a blood filter containing immobilized heparinase. Such a filter could potentially enable heparinization of an extracorporeal circuit without simultaneous heparinization of the patient. The principal findings of our work thus far include (1) increasing volumetric enzyme production over 1000-fold from previously published procedures; (2) purifying heparinase by over 1000-fold from the crude cell extracts; (3) characterizing the biochemical properties of heparinase; (4) isolating the first heparinase inhibitors; (5) immobilizing heparinase with 91% activity recovery and excellent stability; and (6) demonstrating that columns as small as 1.5 mL can remove clinically used quantities of heparin in aqueous medium and in blood.