title: Anticoagulant effects of a low molecular weight heparinoid (Org 10172) in human volunteers and haemodialysis patients.
abstract: Org 10172, a low MW heparinoid derived from animal intestinal mucosal tissue, has a mean molecular weight of 6500 D and a specific activity of 8.0 anti-Xa U/mg. Its elimination half-life after i.v. administration is 18 hours. Six human volunteers received repeated single i.v. injections of 800 and 3200 anti-Xa units of Org 10172, 5000 IU heparin or placebo. Bleeding time, platelet count and plasma beta thromboglobulin were not affected by Org 10172 or heparin. Heparin stimulated ADP-induced platelet aggregation (0.2 uM; p less than 0.05) and inhibited thrombin induced aggregation (0.3 U/ml; p less than 0.05), while the heparinoid lacked these effects. Heparin increased plasma platelet factor 4, whereas Org 10172 had no effect. In contrast to heparin Org 10172 had only a minor effect on the activated partial thromboplastin time and thrombin time, while both compounds induced anti-Xa activity in plasma. In a crossover study in six haemodialysis patients, both heparin and Org 10172 (34.4 and 22.4 anti-Xa units/kg/body weight) successfully prevented clotting of the extracorporeal circuit. Microscopical analysis of the artificial kidney membranes showed that the 34.4 unit Org 10172 dosage was as effective as heparin in preventing fibrin deposition. The haemostatic and coagulation effects were as expected from those observed in the volunteers except that there was a slower elimination of the plasma anti-Xa response. In addition heparin and Org 10172 (34.4 anti-Xa units/kg) inhibited the Xa-induced platelet aggregation (0.5 U/ml; p less than 0.01 and p less than 0.001 respectively).
authors.forename: H
authors.initials: H
authors.lastname: ten Cate
authors.forename: C P
authors.initials: CP
authors.lastname: Henny
authors.forename: J W
authors.initials: JW
authors.lastname: ten Cate
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
authors.forename: M C
authors.initials: MC
authors.lastname: Mooy
authors.forename: S
authors.initials: S
authors.lastname: Surachno
authors.forename: J M
authors.initials: JM
authors.lastname: Wilmink
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006025:Glycosaminoglycans / Q000494:pharmacology / Q000627:therapeutic use*; D006497:Heparan Sulfate; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000502:physiology; D006435:Renal Dialysis; D013918:Thrombin Time; D001620:beta-Thromboglobulin / Q000378:metabolism
chemical_list: D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005170:Factor X; D015951:Factor Xa; D005337:Fibrin; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D010978:Platelet Factor 4; D001620:beta-Thromboglobulin; C035838:danaparoid