Genetically Determined Platelet Reactivity and Related Clinical Implications

Strisciuglio, Teresa; Gioia, Giuseppe Di; Biase, Chiara De; Esposito, Massimiliano; Franco, Danilo; Trimarco, Bruno; Barbato, Emanuele

doi:10.1007/s40292-015-0104-5

Cited by 5 publications

(3 citation statements)

References 59 publications

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“…Nitric oxide synthase 3 plays a key role in platelets function by reducing aggregation. The polymorphisms Glu298Asp and intron4 (an allele) contribute to atherosclerosis development and risk of CAD and also influence platelet reactivity in patients with acute coronary syndromes (ACS) on DAPT (20,21). Furthermore it was recently demonstrated that the effect of Glu298Asp is offset by a loading dose of DAPT in stable CAD patients undergoing elective PCI (22).…”

Section: Platelets Receptorsmentioning

confidence: 99%

Impact of genetic polymorphisms on platelet function and response to anti platelet drugs

Strisciuglio¹,

Franco²,

Gioia³

et al. 2018

Cardiovasc. Diagn. Ther

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Cardiovascular genomic consists in the identification of polymorphic genes responsible for the susceptibility to cardiovascular disease including coronary artery disease (CAD). Genes involved in platelet activation and aggregation play a key role in the predisposition to CAD. A considerable inter-variability of platelet response to agonists and to drugs exists and in particular the hyper-reactivity phenotype seems to be heritable. Besides glycoproteins and receptors expressed on platelets surface whose mutations significantly impact on platelet function, moreover researchers in the last decades have paid great attention to the genes involved in the response to anti-platelet drugs, considering their pivotal role in the treatment and outcomes of CAD patients especially those undergoing PCI. With the outbreak of advanced techniques developed to analyse human genetic footprints, researchers nowadays have shifted from genetic linkage analysis and a candidate gene approach toward genome-wide association (GWAS) studies and the analysis of miRNA-mRNA expression profiles.

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Section: Platelets Receptorsmentioning

confidence: 99%

Impact of genetic polymorphisms on platelet function and response to anti platelet drugs

Strisciuglio¹,

Franco²,

Gioia³

et al. 2018

Cardiovasc. Diagn. Ther

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“…The results of the present study suggest that through the use of the blood tryptase concentration, together with the immunohistochemical investigation for anti-tryptase antibody staining in samples from the lung, glottis, and skin (at the site of administration of medications and contrast medium), it is possible to realize a very reliable diagnostic workflow of anaphylactic death (Figure 5). In fact, previous studies reported in the literature [61][62][63][64][65][66][67][68] have not clearly expressed how to establish a specific diagnosis of anaphylactic death. This diagnostic workflow should be used to establish an anaphylactic reaction as the cause of death with a large margin of certainty.…”

Section: Discussionmentioning

confidence: 99%

Anaphylactic Death: A New Forensic Workflow for Diagnosis

et al. 2021

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Anaphylaxis is a life-threatening or fatal clinical emergency characterized by rapid onset, and death may be sudden. The margin of certainty about the diagnosis of anaphylactic death is not well established. The application of immunohistochemical techniques combined with the evaluation of blood tryptase concentrations opened up a new field of investigation into anaphylactic death. The present study investigated eleven autopsy cases of anaphylactic death, carried out between 2005 and 2017, by the Departments of Forensic Pathology of the Universities of Foggia and Catania (Italy). An analysis of the medical records was carried out in all autopsies. Seven autopsies were carried out on males and four on females. Of the eleven cases, one showed a history of asthma, one of food ingestion, two of oral administration of medications, six did not refer any allergy history, and one subject was unknown. All cases (100%) showed pulmonary congestion and edema; 7/11 (64%) of the cases had pharyngeal/laryngeal edema and mucus plugging in the airway; only one case (9%) had a skin reaction that was found during external examination. Serum tryptase concentration was measured in ten cases, and the mean value was 133.5 µg/L ± 177.9. The immunohistochemical examination using an anti-tryptase antibody on samples from the lungs, pharynx/larynx, and skin site of medication injection showed that all cases (100%) were strongly immunopositive for anti-tryptase antibody staining on lung samples; three cases (30%) were strongly immunopositive for anti-tryptase antibody staining on pharyngeal/laryngeal samples; and eight cases (80%) were strongly immunopositive for anti-tryptase antibody staining on skin samples. We conclude that a typical clinical history, blood tryptase level >40 µg/L, and strongly positive anti-tryptase antibody staining in the immunohistochemical investigation may represent reliable parameters in the determination of anaphylactic death with the accuracy needed for forensic purposes.

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“…As a major metabolizing enzyme, CYP2C19 is involved in catalyzing the bioactivation of many commonly used drugs in humans [ 1 ]. Clopidogrel is a thienopyridine derivative that has antiplatelet effects through the inhibition of platelet adenosine receptors (e.g., P2Y12) after bioactivation by the cytochrome P450 metabolic system [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Distribution of CYP2C19 polymorphisms in Mongolian and Han nationals and the choice of specific antiplatelet drugs

Wang

Hu-ping

2017

Int J Clin Pharm

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Background Individualized medication reviews may improve our understanding of the distribution of CYP2C19 polymorphisms in ethnic populations. Objective To evaluate differences in CYP2C19 gene polymorphisms between Mongolian and Han nationals and determine the effect of adjustments of antiplatelet treatments according to the genetic profile in patients undergoing percutaneous coronary intervention (PCI). Setting Prospective, observational, single-center study. Methods 397 patients diagnosed with acute coronary syndrome were enrolled. Additionally, 186 patients undergoing PCI were given different treatments according to their CYP2C19 genotypes. Patients with the genotype of an extensive metabolizers (EMs; *1/*1) were co-administered aspirin 100 mg/day and clopidogrel 75 mg/day, following a loading dose of 300 mg; intermediate metabolizers (IMs; e.g., *1/*2 and *1/*3) and poor metabolizers (PMs; e.g., *2/*2 and *2/*3) were administered a loading dose of 180 mg ticagrelor, followed by a maintenance dose of 90 mg twice a day. Results In Mongolians, 60.79% of patients were EMs, which was significantly higher than that in Han nationals (P = 0.002). In Han individuals, 62.14% of patients were IMs and PMs, which was significantly higher than that in Mongolians (P < 0.05). Three patients died, and the frequency of adverse events during follow-up was significantly higher in patients given conventional treatment than in patients given tailored treatment (P = 0.039). However, differences in metabolism subtypes did not affect the incidence of adverse reactions. Conclusions There were differences in CYP2C19 polymorphisms between Mongolians and Hans. Effective, safe therapy was achieved by tailoring antiplatelet drug therapy based on genotype.

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Genetically Determined Platelet Reactivity and Related Clinical Implications

Cited by 5 publications

References 59 publications

Impact of genetic polymorphisms on platelet function and response to anti platelet drugs

Impact of genetic polymorphisms on platelet function and response to anti platelet drugs

Anaphylactic Death: A New Forensic Workflow for Diagnosis

Distribution of CYP2C19 polymorphisms in Mongolian and Han nationals and the choice of specific antiplatelet drugs

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