New approaches for anticoagulation in extracorporeal therapy.
The need to fully heparinize patients undergoing extracorporeal therapy often leads to hemorrhagic complications. Two approaches have been used to solve this problem. The first involves full heparinization of blood entering the extracorporeal device followed by the elimination of heparin from the blood returned to the patient using an immobilized heparinase reactor system. Animal studies have demonstrated the successful elimination of heparin's anticoagulant activity using this reactor. The second approach uses very low molecular weight (VLMW) heparins with improved properties. Although low molecular weight heparins and heparinoids have been successfully used in hemodialysis, these preparations are polydisperse mixtures. New VLMW heparins are described which are pure, monodisperse, structurally defined drugs and show improved pharmacokinetics and greater specificity than heparin. The separation of ATIII and HCII mediated activity against factors IIa and Xa may permit extracorporeal therapy with only partial anticoagulation resulting in increased antithrombotic activity with decreased hemorrhagic side-effects. Finally, these VLMW heparins suggest certain desirable structural characteristics in the design blood compatible non-thrombotic synthetic polymers for use in extracorporeal devices.
Linhardt
R J
RJ
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.
Langer
R
R
D004800:Enzymes, Immobilized; D005112:Extracorporeal Circulation; D006470:Hemorrhage / Q000517:prevention & control; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D019763:Heparin Lyase; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D011133:Polysaccharide-Lyases
D004800:Enzymes, Immobilized; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase