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Platelets and the Antiplatelet Drugs: From Bench to Bedside and Back

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (10 July 2023) | Viewed by 8778

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Special Issue Editor

Prof. Dr. Hong-Guang Xie

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Guest Editor

1. Division of Clinical Pharmacology, General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
2. Department of Pharmacology, College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
Interests: antiplatelet drugs; biologics and biosimilars; cardiovascular pharmacology; clinical pharmacology; clopidogrel resistance; complement C4b-binding protein; drug-metabolizing enzymes; drug transporters; hemostasis; inflammation; oxidative stress; personalized medicine; pharmacogenomics; pharmacokinetics; platelet; thrombosis; trimethylamine N-oxide

Special Issue Information

Dear Colleagues,

Circulating platelets, in particular those with hyperactivity, play an essential role in the initiation and progression of thrombotic vascular diseases, such as coronary artery disease and ischemic stroke. Thus, antiplatelet drugs are widely used for the prevention of all thrombosis-associated vascular diseases. On the one hand, the thorough dissection of the physiology and pathophysiology of platelets in their entire life cycle (including young reticulated immature platelets) provides potential therapeutic targets for the discovery and development of novel antiplatelet drugs, such as COX1 inhibitors, P2Y12 receptor antagonists, GP IIb/IIIa inhibitors or receptor blockers, PAR1 receptor blockers, and more. On the other hand, clinical research studies and evaluations of marketed antiplatelet drugs would help us better understand the nature of these drugs for optimal patient care and also for the further improvement of drug research and development. This Special Issue of the Journal of Clinical Medicine, titled "Platelets and the Antiplatelet Drugs: from bench to bedsite and back", will focus on recent advances in basic research and clinical studies of platelets and the antiplatelet drugs (marketed or in the pipeline), all of which lie in the scope of the above-designated title. Contributions on these and related topics are welcome, including original papers and review articles.

Prof. Dr. Hong-Guang Xie
Guest Editor

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Keywords

antiplatelet drug
drug resistance to aspirin or clopidogrel
dual antiplatelet therapy (DAPT)
hemostasis
high on-treatment platelet reactivity (HTPR)
inflammation
personalized medicine
platelet (biochemistry, molecular biology, physiology, and pathophysiology)
systems medicine
thrombosis

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Published Papers (4 papers)

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Research

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14 pages, 728 KiB

Open AccessArticle

Association of ADP-Induced Whole-Blood Platelet Aggregation with Serum Low-Density Lipoprotein Cholesterol in Patients with Coronary Artery Disease When Receiving Maintenance Ticagrelor-Based Dual Antiplatelet Therapy

by Bernadeta Chyrchel, Olga Kruszelnicka, Ewa Wieczorek-Surdacka and Andrzej Surdacki

J. Clin. Med. 2023, 12(13), 4530; https://doi.org/10.3390/jcm12134530 - 6 Jul 2023

Cited by 2 | Viewed by 1843

Abstract

The degree of platelet inhibition in patients undergoing dual antiplatelet therapy (DAPT) affects cardiovascular outcomes after acute coronary syndromes (ACS) and/or percutaneous coronary intervention. Our aim was to search for correlates of residual ex vivo platelet reactivity and circulating soluble P-selectin (sP-selectin), an index of in vivo platelet activation, in patients being treated by DAPT with ticagrelor. Adenosine diphosphate (ADP)-induced platelet aggregability (by multiple electrode aggregometry) and plasma sP-selectin were estimated in 62 stable post-ACS subjects (46 men and 16 women; mean age: 64 ± 10 years; 30 with type 2 diabetes (T2DM)) undergoing maintenance DAPT with ticagrelor and aspirin. These patients did not exhibit heart failure or other relevant coexistent diseases except for properly controlled T2DM, mild renal insufficiency, and hypertension. We also assessed this in 64 subjects on clopidogrel-based DAPT matched for age, sex, and T2DM status. ADP-induced platelet aggregation was below the optimal levels (190–460 arbitrary units (AU) * min) in most patients receiving ticagrelor-based DAPT, especially in those with below-median (<1.9 mmol/L) serum concentrations of low-density lipoprotein cholesterol (LDL-c) (128 ± 61 vs. 167 ± 73 AU * min for below-median and above-median LDL-c, respectively, p = 0.025). In contrast, platelet reactivity did not differ by LDL-c on clopidogrel-based DAPT (246 ± 101 vs. 268 ± 108 AU * min for below-median and above-median LDL-c, respectively, p > 0.4). Plasma sP-selectin was found to be unrelated to serum LDL-c when receiving DAPT with ticagrelor (p > 0.4) or clopidogrel (p > 0.8). In conclusion, our preliminary observational study suggests the association of lower residual ex vivo platelet aggregability with better LDL-c control in patients undergoing ticagrelor-based maintenance DAPT, which does not appear to be reflected by plasma sP-selectin. Whether the serum LDL-c level should be considered among the factors affecting the degree of platelet inhibition for those treated with ticagrelor-based DAPT needs to be investigated in larger studies. Full article

(This article belongs to the Special Issue Platelets and the Antiplatelet Drugs: From Bench to Bedside and Back)

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12 pages, 3316 KiB

Open AccessArticle

Human Nanoplatelets as Living Vehicles for Tumor-Targeted Endocytosis In Vitro and Imaging In Vivo

by Lu Dai, Yehong Liu, Shuang Ding, Xiaowei Wei and Baoan Chen

J. Clin. Med. 2023, 12(4), 1592; https://doi.org/10.3390/jcm12041592 - 17 Feb 2023

Cited by 1 | Viewed by 1822

Abstract

Recent studies have shown human platelets can access the tumor microenvironment by passive diffusion across capillaries or via activated immune cells. In a previous study, we exploited this affinity of platelets for tumor cells as part of a new approach to target tumors with modified platelets. Therefore, the engineering of human nanoplatelets as living vehicles for in vivo tumor-targeted near-infra-red fluorescence (NIRF) imaging and the delivery of cytotoxins to tumor cells by endocytosis are described in this study. Nanoplatelets with an average diameter of 200 nm were prepared by mild sonication of kabiramide C (KabC)-loaded human platelets. The sealed plasma membrane of the nanoplatelets allows them to accumulate and retain membrane-permeable chemicals, such as epidoxorubicin (EPI) and KabC. Tumor-targeted imaging functionalities were engineered on the nanoplatelets by surface-coupling transferrin, Cy5 and Cy7. High-resolution fluorescence imaging and flow cytometry analyses showed that the nanoplatelets loaded with EPI and Cy5 targeted human myeloma cells (RPMI8226 cells) that over-expressed the transferrin receptor. The endocytosis of the nanoplatelets by RPMI8226 cells was transferrin-dependent and induced apoptosis. The test results also showed that the nanoplatelets functionalized with transferrin and Cy7 and injected in mice bearing RPMI8226 cells-derived myeloma xenotransplants accumulated in the tumor tissue and could be used for high-contrast in vivo NIRF imaging of early-stage tumors. Nanoplatelets represent a new class of living nano-vehicles that may efficiently target and deliver therapeutic agents and imaging probes to diseased tissues including tumors. Full article

(This article belongs to the Special Issue Platelets and the Antiplatelet Drugs: From Bench to Bedside and Back)

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11 pages, 1244 KiB

Open AccessArticle

Diurnal Oscillations of Fibrinolytic Parameters in Patients with Acute Myocardial Infarction and Their Relation to Platelet Reactivity: Preliminary Insights

by Joanna Boinska, Marek Koziński, Michał Kasprzak, Michał Ziołkowski, Jacek Kubica and Danuta Rość

J. Clin. Med. 2022, 11(23), 7105; https://doi.org/10.3390/jcm11237105 - 30 Nov 2022

Cited by 1 | Viewed by 1558

Abstract

There is limited information about diurnal changes in fibrinolysis parameters after acute myocardial infarction (AMI) and their relationship with on-treatment platelet reactivity. The aim of this study was to assess tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), α2-antiplasmin (α2-AP) activity, and plasmin–antiplasmin (PAP) complexes in 30 AMI patients taking dual antiplatelet therapy (DAPT), i.e., acetylsalicylic acid and clopidogrel. Fibrinolytic parameters were assessed at four time points (6 a.m., 10 a.m., 2 p.m., and 7 p.m.) on the third day after AMI using immunoenzymatic methods. Moreover, platelet reactivity was measured using multiple-electrode aggregometry, to assess potential differences in fibrinolytic parameters in low/high on-aspirin platelet reactivity and low/high on-clopidogrel platelet reactivity subgroups of patients. We detected significant diurnal oscillations in t-PA and PAI-1 levels in the whole study group. However, PAP complexes and α2-AP activity were similar at the analyzed time points. Our study reveals a potential impact of DAPT on the time course of fibrinolytic parameters, especially regarding clopidogrel. We suggest the presence of diurnal variations in t-PA and PAI-1 concentrations in AMI patients, with the highest levels midmorning, regardless of platelet reactivity. Significantly elevated levels of PAI-1 during the evening hours in clopidogrel-resistant patients may increase the risk of thrombosis. Full article

(This article belongs to the Special Issue Platelets and the Antiplatelet Drugs: From Bench to Bedside and Back)

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Review

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28 pages, 854 KiB

Open AccessReview

The Role of Platelets in the Pathogenesis and Pathophysiology of Adenomyosis

by Sun-Wei Guo

J. Clin. Med. 2023, 12(3), 842; https://doi.org/10.3390/jcm12030842 - 20 Jan 2023

Cited by 7 | Viewed by 2892

Abstract

Widely viewed as an enigmatic disease, adenomyosis is a common gynecological disease with bewildering pathogenesis and pathophysiology. One defining hallmark of adenomyotic lesions is cyclic bleeding as in eutopic endometrium, yet bleeding is a quintessential trademark of tissue injury, which is invariably followed by tissue repair. Consequently, adenomyotic lesions resemble wounds. Following each bleeding episode, adenomyotic lesions undergo tissue repair, and, as such, platelets are the first responder that heralds the subsequent tissue repair. This repeated tissue injury and repair (ReTIAR) would elicit several key molecular events crucial for lesional progression, eventually leading to lesional fibrosis. Platelets interact with adenomyotic cells and actively participate in these events, promoting the lesional progression and fibrogenesis. Lesional fibrosis may also be propagated into their neighboring endometrial–myometrial interface and then to eutopic endometrium, impairing endometrial repair and causing heavy menstrual bleeding. Moreover, lesional progression may result in hyperinnervation and an enlarged uterus. In this review, the role of platelets in the pathogenesis, progression, and pathophysiology is reviewed, along with the therapeutic implication. In addition, I shall demonstrate how the notion of ReTIAR provides a much needed framework to tether to and piece together many seemingly unrelated findings and how it helps to make useful predictions. Full article

(This article belongs to the Special Issue Platelets and the Antiplatelet Drugs: From Bench to Bedside and Back)

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