Extracorporeal enzymatic heparin removal: use in a sheep dialysis model.
Extracorporeal medical devices such as the hemodialyzer rely on systemic heparinization to prevent thrombus formation. Heparin, however, can lead to serious hemorrhagic complications. A blood filter containing immobilized heparinase, a heparin specific enzyme, was used to degrade heparin into small fragments which have significantly less anticoagulant activity than the parent compound. The heparinase filter was tested in the extracorporeal circuit during the hemodialysis of adult sheep. At a blood flow of 200 ml/min, the clearance of heparin varied from 50 to 70 ml/min (N = 16) depending on the amount of immobilized heparinase in the filter. Hemolysis was insignificant as measured by the animals' red cell counts, hematocrit, total hemoglobin and a plasma-free hemoglobin value of 89 +/- 33 mg/dl (N = 16) (less than 1% of the total hemoglobin). The white cell counts dropped to 47 +/- 7% (N = 16) of the initial value at 20 minutes and rebounded to 72 +/- 10% (N = 16) after one hour. The platelet counts decreased to 55 +/- 8% (N = 16) of the initial value after one hour. No change in heparin clearance was observed when reactors were used repeatedly in adult sheep over a 10 week period. The red cell counts, white cell counts, platelet counts, total hemoglobin and hematocrit did not change after 10 weeks of exposure to the device. These results suggest that with further study, heparinase may be useful in removing heparin used to anticoagulate blood in extracorporeal circuits.
Department of Chemical Engineering, Harvard MIT Division of Health Sciences and Technology, Cambridge, Massachusetts.
H
H
Bernstein
V C
VC
Yang
D
D
Lund
M
M
Randhawa
W
W
Harmon
R
R
Langer
D000818:Animals; D004195:Disease Models, Animal; D004867:Equipment Design; D005260:Female; D005417:Flavobacterium / Q000201:enzymology; D006403:Hematologic Tests; D006493:Heparin / Q000097:blood*; D006494:Heparin Antagonists / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use*; D019763:Heparin Lyase; D011133:Polysaccharide-Lyases / Q000096:biosynthesis / Q000494:pharmacology / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000295:instrumentation / Q000379:methods*; D012756:Sheep
D006494:Heparin Antagonists; D006493:Heparin; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase