However, within the absence of any kind of relevant clinical tests, the in vitro strategy pays to in assessing systems of action

However, within the absence of any kind of relevant clinical tests, the in vitro strategy pays to in assessing systems of action. coronary syndromes (ACS)1 and happens after percutaneous coronary treatment (PCI) also, specifically whenever a stent is positioned.2 Periprocedural usage of platelet glycoprotein (Gp) IIb/IIIa (IIbIIIa) receptor (Gp IIb/IIIa) blockers has been proven to reduce the chance of main adverse cardiac occasions (loss of life, CCG-63808 myocardial infarction, and do it again revascularisation) after PCI with or without coronary stenting.3,4 Usage of Gp IIb/IIIa blockers in addition has been shown to reduce event rates in patients with ACS.5C8 Furthermore, combined use of Gp IIb/IIIa antagonists and low dose heparin reduces the risk of ischaemic complications, without increasing the risk of haemorrhage. Long term restenosis of the dilated segment of a coronary artery remains a problem and occurs in up to 30% of patients after PCI even with the use of stents.9,10 Greater activation of inflammatory processes after PCI predicts restenosis, perhaps by stimulating smooth muscle cell proliferation.11,12 Restenosis results from a combination of smooth muscle proliferation, recoil, and incorporation of thrombus9,13,14 and has remained a problem despite the use of Gp IIb/IIIa receptor blockers.3 Persistent platelet activation, despite the abrogation of aggregation by the Gp IIb/IIIa blockers, may play a key part through the generation of plateletCleucocyte conjugates, increased leucocyte activation, and release of inflammatory mediators and growth factors.11,15,16 P selectin, an adhesion molecule, acts as a marker for activated platelets, which contribute to leucocyte conjugate formation by binding P selectin glycoprotein ligand (PSGL)-1.17 At present, before PCI, a bolus of unfractionated heparin (UFH) is given, with or without additional Gp IIb/IIIa blockade. The main limitation of UFH results from its propensity to bind to positively charged proteins and surfaces. Pharmacokinetic limitations are caused by binding of UFH to plasma proteins, platelet proteins, and endothelial cells, resulting in a variable anticoagulant response and the phenomenon of heparin resistance. Although an exact therapeutic dose of low molecular weight heparin (LMWH) required for PCI is still unknown, it has been suggested as an alternative, since it has a predictable dose response, eliminating the need for assessments of coagulation. In addition, the risk of heparin induced thrombocytopenia is lower with LMWH.18 Data from treatment of ACS suggest benefit CCG-63808 in using LMWH rather than UFH.19,20 Therefore, it has been suggested that use of LMWH in preference to UFH in PCI may be beneficial even though randomised controlled comparisons are not yet available. CCG-63808 The two main thrombin receptors on human platelets are protease activated receptor (PAR)-121 and platelet Gp Ib.22 These receptors act synergistically in the platelet response to thrombin through a necessary cofactor role for Gp Ib during PAR-1 activation.23 Activation of Gp Ib by thrombin, in turn, is inhibited by heparin and this is directly proportional to the chain length of the oligosaccharide.24 The possibility, therefore, exists that heparin may provide additional Rabbit Polyclonal to Glucokinase Regulator protection beyond anticoagulation in PCI by inhibiting platelet activation and that protection is related to the molecular weight of the molecule. To understand better the relative merits of using combinations of Gp IIb/IIIa antagonists with UFH and LMWH to control platelet function, we have analysed platelet activation and aggregation in vitro. Our results confirm that heparin provides protection from thrombin induced platelet activation not afforded by Gp IIb/IIIa antagonists and in addition that UFH may be significantly better in this respect than LMWH. METHODS Reagents and antibodies Collagen, thrombin, and ADP were obtained from Sigma Diagnostics (Poole, UK). Adrenaline was obtained from Helena Biosciences (Sunderland, UK). The PAR-1 agonist hexapeptide SFLLRN (thrombin receptor activating peptide.

Related Posts