Investigating the Mechanisms of Hyporesponse to Antiplatelet Approaches

Abstract

Hyporesponsiveness, or resistance, to antiplatelet therapy may be a major contributor to poorer outcomes among cardiac patients and may be attributed to an array of mechanisms—both modifiable and unmodifiable. Recent evidence has uncovered clinical, cellular, and genetic factors associated with hyporesponsiveness. Patients with severe acute coronary syndromes (ACS), type 2 diabetes, and increased body mass index appear to be the most at risk for hyporesponsiveness. Addressing modifiable mechanisms may offset hyporesponsiveness, while recognizing unmodifiable mechanisms, such as genetic polymorphisms and diseases that affect response to antiplatelet therapy, may help identify patients who are more likely to be hyporesponsive. Hyporesponsive patients might benefit from different dosing strategies or additional antiplatelet therapies. Trials correlating platelet function test results to clinical outcomes are required. Results from these studies could cause a paradigm shift toward individualized antiplatelet therapy, improving predictability of platelet inhibition, and diminishing the likelihood for hyporesponsiveness. Copyright © 2008 Wiley Periodicals, Inc.

Influence of Cardiometabolic Risk Factors on Platelet Function

“…Platelets from diabetic patients are more prone to form spontaneous microaggregates [130], to adhesion, to aggregation in response to agonists [131], and to be less sensitive to antiaggregants [132]. Biochemical abnormalities associated with these impairments of platelet function can be detected by elevation of intracellular calcium levels and expression of platelet activation markers including PMPs, which in patients with T2DM can be used as potential predictors of CV outcomes [133].…”

Platelet aggregability and anticoagulant proteins activity during dobutamine stress echocardiography in asymptomatic patients four months after percutaneous coronary intervention

“…Although the mortality rate from IHD declined over last four decades all over the world, it is still responsible for a third of all deaths in the patients older than 35 years 1,2 . An important factor in the disease incidence and complications during the percutaneous coronary interventions (PCI) is a platelet aggregability, changes in these parameters and resistance to antiplatelet therapy [3][4][5][6][7] . The aggregation of platelets and activation process of hemostasis during myocardial ischemia within the physical or mental stress can be an important factor in stent thrombosis after the PCI 4 .…”

“…The most important physiological functions of platelets are: active participating in all phases of hemostasis, both physical and chemical processes, as well as the release and activity of specific platelet factors. In addition, they have a role in the process and maintaining the integrity of the endothelium, phagocytosis, body detoxification and transport of goods [5][6][7][8] . Platelets play a key role in the pathophysiology of thrombosis after the plaque rupture.…”

Description of Response to Aspirin and Clopidogrel in Outpatients With Coronary Artery Disease Using Multiple Electrode Impedance Aggregometry

“…4 Failure of antiplatelet treatment to prevent recurrent thrombotic episodes, also called clinical resistance to antiplatelet treatment, is in part associated with biological inefficiency of aspirin or clopidogrel to inhibit platelet activation and aggregation induced by arachidonic acid or ADP, respectively. 5,6 Clinical resistance to antiplatelet drugs used at fixed recommended doses may also be related with a high residual platelet activation after treatment initiation. [7][8][9][10][11][12] Several laboratory assays, different in their concept, are sensitive to detect high platelet reactivity (HPR) on treatment with aspirin or clopidogrel.…”

“…[7][8][9][10][11][12] Several laboratory assays, different in their concept, are sensitive to detect high platelet reactivity (HPR) on treatment with aspirin or clopidogrel. 5,6 Multiple electrode aggregometry (MEA) performed in whole blood is a point-of-care computerized assay based on the principle of impedance aggregometry. 13,14 Multiple electrode aggregometry and other assays have been mainly studied in trials that evaluated HPR on aspirin or clopidogrel treatment within the first month after the PCI.…”