Multifactorial Background for a Low Biological Response to Antiplatelet Agents Used in Stroke Prevention

Abstract

Effective platelet inhibition is the main goal of the antiplatelet therapy recommended as a standard treatment in the secondary prevention of non-embolic ischemic stroke. Acetylsalicylic acid (aspirin) and clopidogrel are commonly used for this purpose worldwide. A low biological response to antiplatelet agents is a phenomenon that significantly reduces the therapeutic and protective properties of the therapy. The mechanisms leading to high on-treatment platelet reactivity are still unclear and remain multifactorial. The aim of the current review is to establish the background of resistance to antiplatelet agents commonly used in the secondary prevention of ischemic stroke and to explain the possible mechanisms. The most important factors influencing the incidence of a low biological response were demonstrated. The similarities and the differences in resistance to both drugs are emphasized, which may facilitate the selection of the appropriate antiplatelet agent in relation to specific clinical conditions and comorbidities. Despite the lack of indications for the routine assessment of platelet reactivity in stroke subjects, this should be performed in selected patients from the high-risk group. Increasing the detectability of low antiaggregant responders, in light of its negative impact on the prognosis and clinical outcomes, can contribute to a more individualized approach and modification of the antiplatelet therapy to maximize the therapeutic effect in the secondary prevention of stroke.

A Case of Atypical Capsular Warning Syndrome of Long Duration

“…Aspirin and clopidogrel are commonly used for prevention of recurrence of ischemic stroke 17) ; however, patients with low biological response to these antiplatelet agents have a tendency to produce a significant reduction on the therapeutic effect of the antiplatelet drugs, carrying a worse prognosis of ischemic events 17) . The biological response is measured by various platelet function tests which aim to check the degree of aggregation and activation of platelets 17) . In our patient, the precise biological response to the antiplatelet drugs was not evaluated because the platelet function tests were not performed.…”

Antithrombotic and anticoagulation therapies in cardiogenic shock: a critical review of the published literature

“…Systemic inflammatory response syndrome may significantly affect the response to aspirin by alternative pathways of platelet activation with hyperproduction of thromboxane A2 regardless of the arachidonic acid pathways. 11 Catecholamine burst, as a compensatory mechanism and systemic inflammatory response syndrome, may directly activate platelets that are non‐sensitive to aspirin. 12 …”

Biomarkers for Antiplatelet Therapies in Acute Ischemic Stroke: A Clinical Review

“…Other causes for resistance include the pharmaceutical preparation, anion efflux pump, interaction of platelets with other cells like endothelial cells or monocytes, accelerated platelet turnover, and activation of an alternate pathway for metabolism ( 57 ). Metabolic syndromes like diabetes mellitus because of hyper glycation of platelet protein but prediabetes is independent of resistance ( 56 , 58 , 59 ) hypercholesterolemia, increased body weight (obesity) ( 60 , 61 ) smoking ( 62 ), and interaction with some drugs like Proton Pump Inhibitors (PPIs), e.g., esomeprazole and clopidogrel, and Non-Steroidal Anti-Inflammatory Drugs (NSAIDS), e.g., Ibuprofen and Aspirin ( 50 , 53 – 55 , 57 , 63 , 64 ). Examples of antiplatelet resistance causes are shown in Figure 1 .…”

“…So, it is important to measure the inhibition of the platelet function in patients with AIS who have HTPR ( 72 ). The different platelet function testing methods are bleeding time, light transmission platelet aggregation (LTA), impedance platelet aggregation, lumi-aggregometry, and tests based on platelet function methods combined with viscoelastic tests, such as Thromboelastographs (TEGs)/platelet mapping systems, Rotational Thromboelastometry (ROTEM) platelets, and others, where Flow Cytometry is used to test the platelet activation, and Radio- or Enzyme-Linked Immuno Assay measure the thromboxane A2 metabolites ( 8 , 57 , 73 – 75 ).…”