Pentosan polysulfate sodium has been marketed for over fifty years for the treatment of subacute or chronic arteriosclerotic and thrombotic vascular diseases and the follow-up treatment after injection therapy for acute situations and for prophylaxis. Experiments showed that pentosan polysulfate sodium inhibited thrombin-induced platelet aggregation in platelet-rich human plasma (11). Scully and Kakkar (10) revealed heparin cofactor II to be the most important cofactor of in the antithrombin effect of pentosan polysulfate sodium, as verified in healthy volunteers by Dol (8).

It seems reasonable to conclude that pentosan polysulfate sodium inhibits thrombin-induced platelet aggregation by two pathways, indirectly by inhibition of the endogenous coagulation cascade and, directly through heparin cofactor II. Synergistic effects the lipolytic effect of pentosan polysulfate sodium is based on the release of lipoproteinlipase. In patients with increased blood lipid levels, the drug acts to decrease total cholesterol, triglycerids and beta-lipoprotein concentrations which improve the beta/alpha-lipoprotein relationship.
There can be no doubt that pentosan polysulfate sodium causes a substantial inhibition of platelet aggregation in vivo, an ability of clear significance to antithrombotic therapy. On these grounds, the administration of pentosan polysulfate sodium as a thrombocyte aggregation blocker has become a routine therapy, for example in vascular surgery in several countries (9).

An increase of fibrinolysis by activation of the endogenous pathway via factor XII and prekallikrein was shown. The activation of antithrombin III isoforms by heparan sulphate glycosaminoglycans and other sulphated polysaccharides, for example pentosan polysulfate sodium, resulted in thrombolysis (1, 3, 4). Joffe demonstrated a therapeutic effect in prevention of postoperative deep vein thrombosis (2). Vinazzer (7) and Szirmai (6) showed a reduction in the incidence of recurrent cerebrovascular events by pentosan polysulfate sodium - ibidem. 

References

1) Carlson TH, Kolman MR, Piepkorn M: Activation of antithrombin III isoforms by heparan sulphate glycosaminoglycans and other sulphated polysaccharides. Blood Coagul Fibrinolysis. 1995; 6: 474-480.
2) Joffe S: Drug prevention of postoperative deep vein thrombosis. A compararative study of calcium heparinate and sodium pentosan polysulfate. Arch Surg. 1976; 111: 37-40.
3) Klauser RJ: Induction of fibrinolysis by polyanions in human plasma. Thromb Haemost. 1988; 60: 324-327.
4) Marsh NA, Gaffney PJ: The effect of pentosan polysulphate (SP54) on the fibrinolytic enzyme system. An experimental animal study. Folia Haematol Int Mag Klin Morphol Blutforsch. 1986; 113: 255-261.
5) Nagasaki T, Lieberman MA: Heparin potentiates the action of plasma membrane-associated growth stimulatory activity. J Cell Physiol. 1987; 133: 365-371.
6) Szirmai I, Kamondi A. Perfusion. 1993; 8/93: 314-320.
7) Vinazzer H: [Prevention of recurrence of cerebrovascular thromboses. A randomized comparative study of acetylsalicylic acid and sodium pentosan polysulfate]. Fortschr Med. 1987; 105: 79-85.
8) Dol F, Sie P, Dupouy D, Boneu B: Effect of pentosan polysulphate administration in man on the formation of covalent complexes between heparin cofactor II and thrombin generated in plasma by contact activation. Thromb Haemost. 1986; 56: 295-298.
9) Kollár L et al.: Internal carotid stent implantation with angioscopic control. Acta chirurgica Hungarica. 1997; 36: 168-169.
10) Scully MF, Kakkar VV: Identification of heparin cofactor II as the principal plasma cofactor for the antithrombin activity of pentosan polysulphate (SP54). Thromb Res. 1984; 36: 187-194.
11) Sie P, Fernandez F, Caranobe C, Gabaig AM, Boneu B: Inhibition of thrombin-induced platelet aggregation and serotonin release by antithrombin III and heparin cofactor II in the presence of standard heparin, dermatan sulfate and pentosan polysulfate. Thromb Res. 1984; 35: 231-236.