Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Abstract

It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low-or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

The Impact of CYP2C19 Loss-of-Function Polymorphisms, Clinical, and Demographic Variables on Platelet Response to Clopidogrel Evaluated Using Impedance Aggregometry

“…The frequency of CYP2C19-reduced function genotypes (IM and PM) shows wide interethnic variation ranging from 20% to 65% in different populations. 15,16 In our population, the frequency of the genotypes mentioned earlier was 38.9%.…”

Effects of Omega-3 Polyunsaturated Fatty Acids and Their Metabolites on Haemostasis—Current Perspectives in Cardiovascular Disease

“…A meta-analysis of 15 randomised controlled trials provided evidence that omega-3 PUFAs inhibited blood platelet aggregation [ 22 ]. Marine omega-3 PUFAs were also observed to overcome aspirin resistance (acetylsalicylic acid (ASA)) [ 28 , 55 ]. In studies on laboratory animals, it was demonstrated that ASA enhanced the antiplatelet effect of fish oil [ 56 ].…”

Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions

“…High percentage of individuals usually experiences antiplatelet therapy resistance that impairs successful prevention of cardiovascular events, and some determinants of resistance to antiplatelet therapy are gender responsive [141][142][143][144][145][146]. A prospective study on 160 patients with stable coronary heart disease (118 men and 42 women, aged 65:2 ± 7:8 years), indeed, showed a sex-related response to long-term double antiplatelet therapy (75 mg/day aspirin and clopidogrel for three months): female gender was more predisposed to resistance to both aspirin and clopidogrel compared to men [19].…”