Relative effects of heparin and sulodexide on prevention of thrombus formation and growth

ABSTRACTS

S162

OF 12TH NATIONAL

Vol. 70, Suppl. 1

CONGRESS

s 09 PHARMACODYNAMICPROPERTIES OF A NEW LOW MOLECULARWEIGHT HEPARIN, PARNAPARIN. Job Harenberg, 1st Medical Department, Faculty of Clinical Medicine, Mannheim, University of Heidelberg, Germany. Parnaparin is a low molecular weight heparin with a specific activity of 90 anti-factor Xa units-mg. Following the intravenous administration of increasing doses, markedly higher anti-Xa and lower anti-IIa/APTT activities were detected with respect to those

following

unfractioned

heparin

administration.

A dose-re-

sponse relationship as to the anti-Xa activity was clearly ted, with much higher values for areas under the activity

detec curve<

of anti-Xa than of anti-IIa activity. Following the subcutaneous (SC) administration of increasing doses, the same clear-cut sepa ration between anti-Xa and anti-IIa/APTT activities was evidenced, the former being noticeably more marked than the latter when corn pared to unfractionated heparin administration. The anti-Xa pharmacodynamic effect showed an evident dose-response relationship, confirmed by the rising values of the area under the activity curves

and of the

plasma

half-lives.

period of 7 days, the pharmacodynamic confirmed a lack of accumulation.

After values

a SC administration at the

steady-state

s 10 GLYCOSAMINOGLYCANS: PHARMACOLOGICAL PROPERTIES AND METHODS OF ASSESSING CLINICAL EFFICACY. G.M. Andreozzi and S.Signorelli, Institute of Internal Medicine “A. Francaviglia”, Chair of Angiology, University of Catania, Italy. Clinical efficacy of glycosaminoglycans (GAGS) is based upon their antithrombotic, fibrinolytic and antiatherogenic activities. Antithrombotic activity: GAGS accelerate thrombin inhibition by antithrombin III and heparin cofactor II. They have been shown to exert antithrombotic effect in animal models and in humans, particularly in the prevention of postoperative venous thrombosis. Reduction of restenosis and of miointimal proliferation after carotid surgery has also been reported. Fibrinolityc activity: evidence of the profibrinolityc activity of GAGS comes from in vitro and in vivo studies. The proposed mechanisms are through stimulation of the release of t-PA, inhibition of PAI and enhancement of plasminogen activation induced by physiological activators. Recent studies on animal models have documented actual lytic effects of GAGS and especially of low molecular weight dermatan sulfate on preformed thrombi. Antiatherogenic activity: this property has been evaluated since long time ago in studies on membrane phospholipids and on hypolipemic capacity. Some epidemiological studies have also shown a reduction of cardiovascular events in patients with previous ischemic attacks and stroke. There are ongoing studies with the eco-duplex and color-flow-mapping methods which are new tools potentially useful to evaluate the effect of these drugs on the vessel wall. An increase of the elastic tone of the arterial wall by administration of GAGS in patients with peripheral arterial disease has been reported by studies employing plethysmographic and doppler methods. This activity is more evident in the initial phase of the arteriopathy and in diseases associated with substantial damage of the wall as in case of hypertension and diabetes. ‘The GAGS improve vascular permeability as shown by the reduction of microproteinuria in patients with the syndrome ot%immestiel~Wilson~~