THE EFFECTS OF SULFATED POLYSACCHARIDES ON INHIBITION OF THROMBOSIS INDUCED BY DIFFERENT STIMULI

Higher doses of heparin are usually required to achieve a therapeutic effect in patients undergoing elective hip surgery than in patients with idiopathic deep vein thrombosis (DVT). One explanation for this difference is that more heparin is required to prevent thrombosis in hip surgery them recurrent thrombosis in DVT, because the stimulus initiating thrombus formation in each situation is different. This suggests that different procoagulant stimuli may be more or less sensitive to inhibition by heparin. To test this possibility, we measured the effects of heparin (SH), pentosan polysulfate (SP54), and dermatan sulfate (DS) on inhibition of thrombus formation induced by tissue thromboplastin (TTP, 1 mgAg), thrombin (Ha, 1 UAg)/ or Factor Xa (Xa, 20 μt/kg) using a jugular vein/hypercoagulation/stasis ipggel in rabbits. Thrombus size was measured as the amount of ¹²⁵I-fibrin incorporated into a thrombus formed in jugular veins of rabbits, treated with varying concentrations of SH, SP54 or DS. First, we established the dose of each sulfated polysaccharide (SPS) that was required to inhibit thrombus formation induced by TTP by ∼75%. We then used these doses to assess their ability to inhibit thrombus formation induced by Ha or Xa. SH and SP54 were less effective in inhibiting Ila-induced thrombus formation (<62%), while DS was more effective and inhibited thrombus formation by 95%. In contrast, the doses of SP54 and DS which inhibited TTP-induced thrombosis by ∼75%, inhibited Xa-induced thrombus formation by 60 and 71% respectively, while SH inhibited Xa-induced thrombus formation by 98%. We conclude that sensitivity to inhibition of the 3 different procoagulant stimuli by the various SPS, differs significantly. The choice of SPS as an antithrombotic agent should take into consideration the stimulus initiating thrombosis in each clinical situation.