The effect of heparin fragments of different molecular weights on experimental thrombosis and haemostasis.
The effect of heparin fragments of different molecular weights has been compared with that of conventional sodium heparin on experimental thrombosis in vivo and ex vivo and experimental haemostasis in vivo. In the first part of the study fragments of different molecular weights were given (4,900, 6,500, 9,500 and 22,200 dalton). All preparations including the control gave a significant prolongation of the haemostatic plug formation time in the rabbit mesenteric microcirculation, and all except the fragment with the lowest molecular weight reduced the frequency of jugular vein thrombosis (induced by a combination of endothelial denudation and stasis). There was a correlation between the XaI activity of the different heparin fragments and frequency of thrombosis. Using an ex vivo method (modification of Chandler's model) a dose dependent lag phase until start of thrombus formation was found. In the second part of the study a dose response investigation was made comparing different doses of a fragment (6,500 dalton) with conventional heparin in the same XaI doses (10, 30 and 60 units/kg). Sodium heparin in the highest dose prolonged the haemostatic plug formation time whereas none of the fragment doses did. The lowest dose both of the fragment and conventional heparin did not reduce the frequency of thrombosis, whereas the two higher doses did. Thus it may be possible to obtain preventive effect on thrombus formation with a heparin fragment.
D000818:Animals; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000378:metabolism; D019763:Heparin Lyase; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000494:pharmacology; D011133:Polysaccharide-Lyases / Q000378:metabolism; D011817:Rabbits; D013927:Thrombosis / Q000517:prevention & control
D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D005170:Factor X; D006493:Heparin; D015951:Factor Xa; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase