A filter device for the prevention of both heparin- and protamine-induced complications associated with extracorporeal therapy.
When extracorporeal blood circulation (ECBC) is used, systemic heparinization is necessary to prevent clotting of the blood in the extracorporeal circuit. However, the high circulating heparin concentration needed often leads to bleeding complications. To avoid these, protamine, a heparin antagonist, is administered at the conclusion of the ECBC procedure to reverse the anticoagulant activity of heparin. Intravenous administration of protamine can cause hypotension and shock. To date, there has been no real alternative to control the bleeding risks associated with systemic use of heparin and the adverse effects resulting from heparin reversal with protamine. A novel approach that might control both the heparin- and the protamine-induced complications is suggested. It consists of placing a blood-compatible filter device containing immobilized protamine (a protamine filter) at the distal end of the ECBC apparatus. The filter removes heparin after heparin serves its anticoagulant purpose in the extracorporeal circuit and before blood is returned to the patient. The filter also allows for an external protamine treatment. Since protamine toxicity results from the direct contact of protamine with cells of the liver, lungs, and other organ tissues, the use of an external protamine treatment would minimize it. Protamine was covalently immobilized onto a cellulosic hollow fiber bundle obtained from a clinically used hemodialyzer. The bundle was accessed to the vascular system of a dog by femoral artery and vein cannulation. In in-vivo experiments the protamine-bound fiber bundle not only removed heparin from the extracorporeal circuit, but also caused no clinically significant hemodynamic change in the animal.(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
V C
VC
College of Pharmacy, University of Michigan, Ann Arbor 48109-1065.
Teng
C L
CL
Kim
J S
JS
D000327:Adsorption; D000380:Agranulocytosis / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D001672:Biocompatible Materials; D004285:Dogs; D005112:Extracorporeal Circulation / Q000295:instrumentation*; D005240:Feasibility Studies; D005260:Female; D005374:Filtration / Q000295:instrumentation; D006439:Hemodynamics / Q000187:drug effects*; D006493:Heparin / Q000009:adverse effects* / Q000494:pharmacology; D011479:Protamines / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
D001672:Biocompatible Materials; D011479:Protamines; D006493:Heparin