Blood filter, heparinase

We propose a new approach that would allow the full heparinization of the extracorporeal device, yet could enable, on-demand, elimination of heparin in the patient s bloodstream. This approach consists of a blood filter containing immobilized heparinase, which could be placed at the effluent of any extracorporeal device (Figure 1). Such a filter could theoretically be used to eliminate heparin after it had served its purpose in the extracorporeal device and before it returned to the patient. In this chapter we discuss our efforts to develop such a filter. Our work has focused on several areas (1) enzyme production (2) enzyme purification (3) characterization of heparinase (4) immobilization of heparinase and (5) in vitro testing of immobilized heparinase. 

Figure 1. Proposed heparin circuit. The extracorporeal device could be a renal dialysis unit or a pump-oxygenator. The heparinase reactor could be part of a blood filter to be used either continuously (in which case heparin would, be added, continuously at the start of the circuit) or at the end of an operation. Heparin could thus be confined to the extracorporeal circuit.

At present, synthetic blood filters are routinely placed at the effluent of extracorporeal devices such as the pump-oxygenator or artificial kidney to remove clots or aggregates formed during the perfusion. The filters used in oxygenators can be as large as 2 L, whereas those used in renal dialysis are only several milliliters. With further development, heparinase could be immobilized to polymers in these filters. In this case, the filter could remove both clots and heparin. 

Fig. 13. Clearance of heparin by the heparinase filter at a blood flow of 120 mL/min as a function of time. Four experiments were conducted for each animal. Broken lines represent the model predictions the closed circles are the experimentally determined clearances. Each point is the mean of three measurements, and the standard deviations are within the size of the symbols in all cases [from Bernstein and Langer (47)].

---