Thromb Haemostasis
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Dual antiplatelet therapy with aspirin and clopidogrel is currently the standard therapy after coronary stent implantation to prevent a life-threatening stent thrombosis. However, a variety of procedural and individual factors contribute to the individual patient risk and have to be taken into account to allow for an individual recommendation for both the duration and intensity of the antiplatelet therapy. Obviously, the benefit of the prevention of stent thrombosis by antithrombotic therapy has to outweigh the risk of severe bleeding complications. ⋯ However, in a subgroup of high-risk patients there is insufficient evidence for the benefit of conventional dual antiplatelet regimen. These include i) patients with an indication for anticoagulation, ii) patients with urgent need for an operation requiring a perioperative withholding of antiplatelet therapy, as well as iii) clopidogrel low responders. This review aims to provide a stratification to define patient collectives who may benefit from more individualized antithrombotic regimens on behalf of currently available literature and guidelines.
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Comparative Study
Selective inhibition of the platelet phosphoinositide 3-kinase p110beta as promising new strategy for platelet protection during extracorporeal circulation.
Extracorporeal circulation (ECC) is used in cardiac surgery for cardiopulmonary bypass as well as in ventricular assist devices and for extracorporeal membrane oxygenation. Blood contact with the artificial surface and shear stress of ECC activates platelets and leukocytes resulting in a coagulopathy and proinflammatory events. Blockers of the platelet glycoprotein (GP) IIb/IIIa (CD41/CD61) can protect platelet function during ECC, a phenomenon called "platelet anaesthesia", but may be involved in post-ECC bleeding. ⋯ Tirofiban also inhibited ECC-induced beta-thromboglobulin release. The observed inhibition of platelet-ECC interaction and platelet activation by tirofiban contributes to explain the mechanism of "platelet anaesthesia". TGX-221 represents a promising alternative to GP IIb/IIIa blockade and should be further investigated for use during ECC in vivo.
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In addition to their anticoagulant activity, unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) have important immunomodulatory properties. However, different studies have reported conflicting pro- and anti-inflammatory effects in association with heparin. Moreover, the molecular basis for these heparin effects on inflammation remains unclear. ⋯ In ex-vivo whole blood experiments, pro-inflammatory effects (increased IL-1beta and IL-8 following LPS-stimulation) of heparin were also observed, but only at supra-therapeutic doses (10-200 IU/ml). Our data demonstrate that in the absence of LBP, the direct effect of heparin on LPS-stimulated monocytes is anti-inflammatory. However in whole blood, the immunomodulatory effects of heparin are significantly more complex, with either pro- or anti-inflammatory effects dependent upon heparin concentration.