Anti-platelet activity

Because of its powerfiil vasodilator action sodium nitroprusside is often used to treat vascular emergencies associated with hypertensive crisis. Since this compound shows some anti-platelet activity both in vitro and in vivo (Levin et al 1982, Hines and Barash 1989) its acute clinical effects may also be mediated, in part, through inhibition of platelet function. Recently, sodium nitroprusside was administered intrapericardially to treat experimentally induced coronary Arombosis in dogs (Willerson et al 1996). As this route of administration of sodium nitroprusside produced less vasodilatation than systemic one, localized administration of this dmg may offer new therapeutic possibilities for the treatment of the coronary thrombosis. 

Indometacin should probably not be used postopera-tively in patients with an increased risk of bleeding (SEDA-8, 103), because of its anti-platelet activity. 

Tripathi, Y.B., S. Pandey, and S.D. Shukla. 1993. Anti-platelet activating factor property of Rubia cordfolia Linn. Indian. Exp. Biol. 31(6) 533-535. 

Compared to heparin, the sulfated chitosan has been shown to possess high anticoagulant potency. Unlike heparin, sulfated chitosan does not show anti-platelet activity, which causes excessive bleeding in patients (Nishimara et al. 1998). 

Ethyl-2 [ (Z)-hydroxyiminol] -5-nitro-3( )-hexene-amide (FK409) is a semi-artifidal fermentation product of Streptomyces griseosporeus No. 16917 that spontaneously generates NO and possesses potent vaso-relaxant and anti-platelet activities (Fukuyama et al. 1995). It is relative unstable, with a half-life of approximately 45 min at 37 C in phosphate buffer. FK409 has been reported to attenuate experimental liver (Ohmori et al. 1998), cardiac (IsoNO et al. 1993), pulmonary (Takeyoshi et al. 

An imidazoquinazoline constitutes still another compound that does not fall in the classification of a nonsteroid antiinflammatory agent yet shows good platelet anti aggregating activity. Condensation of benzyl chloride 128 with the ethyl ester of glycine gives alkylated product... 

A thrombotic tendency is present in diabetes due to an imbalance between prostacyclin and thromboxane. Lipid peroxides and newly generated free radicals are thought to inhibit the vasodilator and anti-platelet effects of endothelial-derived prostacyclin, but stimulate platelet cyclooxygenase activity, thereby promoting the production of thromboxane A2. This leads to vasoconstriction and platelet aggregation - the concept of peroxide vascular tone (Halliwell and Gutteridge, 1989). 

Detwiler and co-workers were the first to demonstrate a role for csPDI in platelet physiology (Chen et al, 1995 Essex et al, 1995). Essex and co-workers (1999, 2001) and Hogg and co-workers (Burgess et al., 2000) showed that the inactivation of csPDI with anti-PDI antibodies and thiol alkylating agents inhibited platelet activation and aggregation. Recent studies have identified two distinct activities for csPDI. 

CysNO is a potent anti-platelet agent Like other nitrosothiols, it increased the intracellular GMP level in platelets in vitro and inhibited collagen-induced platelet aggregation and ADP-induced activation of GP Ilb/IIIa on the platelet surface [45, 47]. However its potency to release NO, stimulate platelet soluble GS and elevate intracellular platelet cGMP was higher than of GSNO [47, 72]. 

The balance of opposing pro- and anti-platelet forces determines the overall hemostatic response. Successful hemostasis is achieved when assorted signal-transduction systems, mediators, white blood cells, and platelet receptors for agonists and adhesion molecules overcome the local resistance against platelet activation to generate... 

Tab. 12.1 NO donors examined in clinical trials for anti-platelet/anti- thrombotic activity.

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