Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:New approaches for anticoagulation in extracorporeal therapy. 283 16

Dermatan sulphate does not catalyse the inactivation of factor Xa. However, the low molecular weight (LMW) dermatan sulphate Desmin 370 has been shown to generate circulating anti-Xa activity following administration to humans. Using a single batch of Desmin 370, we measured 3 U/mg of anti-Xa activity by amidolytic assay in vitro. The material responsible for this activity had a lower molecular weight range (6000 and 1800 Da) than Desmin 370 and was more highly sulphated than the bulk of the drug. Heparinase digestion of Desmin 370 eliminated 90% of the in vitro anti-Xa activity without significantly interfering with its ability to potentiate inactivation of thrombin by HCII, suggesting that the anti-Xa activity is not due to dermatan sulphate and is probably heparin. When 125I-labelled Desmin 370 together with 40 mg/kg carrier drug was administered intravenously to a rabbit, anti-Xa activity was readily detectable in the plasma for up to 10 h and had a longer half-life than the sulphated radiolabel. Most of this anticoagulant activity was recovered from the plasma by Polybrene affinity chromatography and was probably a sulphated glycosaminoglycan. Administration of the heparinase-digested drug to a rabbit resulted in 70% less anti-Xa activity than the undigested drug. We conclude that Desmin 370 contains detectable quantities of biologically active low molecular weight heparin, which is responsible for persistent anti-Xa activity following intravenous administration.
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PMID:Low molecular weight heparin is responsible for the anti-Xa activity of Desmin 370. 881 78