Antithrombotic strategies in elderly patients with acute coronary syndrome

Central illustration. Anti-thrombotic strategies in patients with acute coronary syndrome. ACS: acute coronary syndrome; ADP: adenosine diphosphate; CAD: coronary artery disease; CRP: C-reactive protein; IL-6; interleukin-6; DAPT: dual antiplatelet therapy; GRACE: Global Registry of Acute Coronary Events; NSTEMI: non-ST-segment elevation myocardial infarction; PAI-1: plasminogen activator inhibitor-1; PCI: percutaneous coronary intervention; PG12: prostaglandin 12; PPI: proton pump inhibitor; PRECISE-DAPT: PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy; REACH: REduction of Atherothrombosis for Continued Health; STEMI: ST-segment elevation myocardial infarction; TIMI: Thrombolysis In Myocardial Infarction; Vwf: von Willebrand factor.

     

Irreversible oxidations of platelet proteins after riboflavin-UVB pathogen inactivation

Pathogen inactivation technologies are known to alter in vitro phenotype and functional properties of platelets. Because pathogen inactivation generates reactive oxygen species, oxidative stress is considered as one of the plausible cause at the origin of the platelet storage lesion acceleration after treatment. To date proteomics has been used to document the protein variations to picture out the impact. Here, platelet concentrates were prepared from buffy-coats in Intersol additive solution, leukoreduced and pathogen inactivated using a riboflavin/UVB treatment. At day 2 of storage the platelet proteomes of control (untreated) and treated platelet concentrates were investigated against the site specific oxidation by liquid chromatography coupled to tandem mass spectrometry in a shotgun experiment. The shotgun approach detected 9350 peptides (and 2534 proteins) of which 1714 were oxidized. Eighteen peptides were found exclusively oxidized in treated platelets whereas 3 peptides were only found oxidized in control. The present data evidenced an interference with several proteins involved in platelet aggregation and platelet shape change (such as talin and vinculin).     

Consensus and controversies in platelet transfusion: Trigger for indication, and platelet dose

Platelet transfusion is about to commemorate its 50th year since its introduction in therapeutics. It is then surprising to see, that in spite of reaching this respectful age, we have not been able to definitely establish all the aspects related to its clinical use. Some of these facets are platelet transfusion threshold and the platelet dose to administer. Historically, two different transfusion triggers have been used for prophylactic and therapeutic platelet transfusions. For prophylactic platelet transfusion an increasing body of evidences suggests that a transfusion trigger of 10 x 10(9) per liter is appropriate for most clinical settings. In contrast, evidence for supporting a certain therapeutic transfusion trigger is lacking. Nevertheless, there is consensus that the platelet count should not be allowed to fall below 50 x 10(9) per liter in patients with acute bleeding. Another important aspect still pending of clear definition is the issue of the platelet dose to be transfused. It has been addressed by some small studies but a definite answer to this important clinical issue is, at least so far, still pending. The results of two ongoing trials, one sponsored by NIH through the Clinical Trials Network in Transfusion Medicine and Hemostasis and the other promoted by the BEST Collaborative Group are expected to help us to clearly defining the more effective and efficient way to transfuse platelet concentrates.     

Quel traitement antithrombotique après un remplacement valvulaire aortique percutané ?

The performance and indications of transvalvular aortic valve implantation or TAVI has considerably expanded and is now the first therapeutic line option in the management of severe aortic stenosis. The targeted population shares both high risk of ischemic complications, particularly stroke or subclinical leaflet thrombosis of the bioprothesis, as well as hemorrhagic complications, strongly correlated to death. Based on previous experience with intracoronary stents, a dual antiplatelet therapy has been recommended by experts’ consensus. This paradigm is now challenged by the observed increased risk of hemorrhagic complications without a reduction of ischemic events. Moreover, the role of non-vitamin K oral anticoagulant in patients undergoing TAVI remains to be determined. Several large ongoing randomized controlled trials will likely change our practice within the next coming year.     

Stratégie de prise en charge d’un patient porteur d’endoprothèses coronaires pharmacoactives à haut risque thrombotique pour une gastrectomie totale

We report the case of a 70-year-old patient, with two drug-eluting stents (DES), scheduled for a complete gastrectomy for a gastric cancer. This case underlines management problems regarding a patient with a high risk of DES thrombosis in case of AAP withdrawal and a high risk of bleeding in case of AAP maintenance. At this time, no evidence-based recommendation is available for clinicians to manage these patients. Our strategy was therefore based on platelet function monitoring test, which is however neither available in clinical practice nor validated to predict haemorrhagic risk. Several biologic tests are under study; they could be useful to guide perioperative management of antiplatelet therapy in the clinical setting of surgical patients with DES.     

Variable extent of platelet responsiveness to clopidogrel inhibition: "clopidogrel resistance"?

During percutaneous coronary angioplasty, platelet inhibition by clopidogrel and aspirin has drastically decreased the risk of thrombotic occlusion of the stented vessels. However, despite the widespread use of these drugs, the incidence of acute or subacute stent thrombosis remains elevated, concerning 1 to 2% of the treated patients. Considerable differences in the responsiveness to clopidogrel could be observed, suggesting a possible underlying biological resistance. "Clopidogrel resistance" has recently been associated to an increased risk of thrombotic events following coronary angioplasty. Variations in enteric absorption, biotransformation in the liver by the CYP3A4, changes in the ADP receptor P2Y12, abnomalies of intraplatelet signal transduction, extent of platelet activation, class angina, diabetes mellitus may account for the considerable interindividual response variability widely reported. In this view, laboratory tests evaluating "clopidogrel resistance" might be useful tools for the identification and follow-up of patients at higher thrombotic risk. Indeed, in these patients, further platelet inhibition can be achieved by higher doses of clopidogrel.