INCREASED PLATELET RESPONSIVENESS FOLLOWING CORONARY STENTING - HEPARIN AS A POSSIBLE ETIOLOGIC FACTOR IN STENT THROMBOSIS

Aims Platelet activation may be a determinant of thrombotic and resten otic complications following intracoronary stenting. In order to measu re the effect of stenting on platelet activation antigen expression we used whole blood flow cytometry in 18 patients undergoing Palmaz-Scha tz stenting (treated with full anticoagulation) and compared these wit h a group of 18 patients undergoing elective angioplasty. The effects of low molecular weight heparin and unfractionated heparin on platelet behaviour were also studied, both in vitro and in vivo to determine t he contribution of prolonged heparin therapy to platelet activation fo llowing stenting. Methods and Results Fibrinogen binding to activated GPIIb-IIIa, and surface expression of P-selectin, GPIb and GPIIb-IIIa antigens were measured in unstimulated peripheral blood samples (rest) and on stimulation with adenosine diphosphate (0.1-10 mu mol.l(-1)) a nd thrombin (0.02-0.16 U.ml(-1)). No changes were seen in resting samp les following angioplasty or stenting. Agonist responsiveness was unal tered after angioplasty, but in stented patients antigen expression in response to thrombin was significantly reduced (P less than or equal to 0.04), whilst the adenosine diphosphate response was significantly increased (P = 0.01). Similar effects were observed in patients with u nstable angina treated with either low molecular weight heparin or unf ractionated heparin in vivo. In vitro, both unfractionated and low mol ecular weight heparin inhibited thrombin-induced platelet activation, but stimulation of adenosine diphosphate responses was more marked wit h unfractionated than low molecular weight heparin. Conclusions There was a significant increase in platelet responsiveness to adenosine dip hosphate following intracoronary stenting in patients treated with con ventional anticoagulants. This was probably a consequence of treatment with heparin. Activation of platelets by heparin may explain the incr eased rate of stent thrombosis in patients treated with anticoagulant therapy. Low molecular weight heparins stimulate platelets less than u nfractionated heparin.