Effects of an enzymatically depolymerized heparin as compared with conventional heparin in healthy volunteers.
A low molecular weight heparin (LMW-heparin) with a mean molecular weight of 4900 dalton was prepared by controlled enzymatic depolymerization of conventional porcine mucosal heparin. The effects of 2,500, 5,000 and 10,000 U (XaI; 29, 58 and 116 mg) on factor Xa inhibition (XaI), factor IIa inhibition (IIaI), APTT, AT III and platelet count were compared to those of 5,000 U (XaI; 26 mg) of conventional heparin given s.c. to 6 healthy volunteers. 5,000 U (XaI; 58 mg) of LMW-heparin was given i.v. A dose related response with regard to the XaI and the IIa-inhibitory activities with peak values at 4 hours after the s.c. injections was obtained. An increase of the XaI/IIaI ratio over the time after injection was seen only after i.v. administration of the LMW-heparin. The APTT was only slightly prolonged and remained within normal range after s.c. injection. AT III and platelet counts were unaffected. The biological half life of the LMW-heparin was 111 minutes if assayed by Xa inhibition, 76 minutes if assayed by IIa inhibition and 40 minutes if assayed by APTT. A strong correlation between the XaI activities obtained and body weight was seen, indicating that LMW-heparin should be administered individually according to body weight.
D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D001822:Body Burden; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D005260:Female; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D019763:Heparin Lyase; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010314:Partial Thromboplastin Time; D011108:Polymers; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011487:Protein Conformation; D011516:Prothrombin / Q000037:antagonists & inhibitors
D011108:Polymers; D000990:Antithrombin III; D011516:Prothrombin; D005170:Factor X; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase