Review Article Aspirin Resistance, Platelet Turnover, and Diabetic Angiopathy: A 2011 Update Matteo Nicola Dario Di Minno ⁎, Roberta Lupoli, Nicola Macarone Palmieri, Anna Russolillo, Agostino Buonauro, Giovanni Di Minno Department of Clinical Experimental Medicine, Regional Reference Centre for Coagulation Disorders; Napoli, Italy abstract article info Article history: Received 19 September 2011 Received in revised form 10 November 2011 Accepted 10 November 2011 Available online 3 December 2011 Keywords: aspirin resistance platelet turnover pairs of aggregating agents stored platelets mouse anti-thrombotic assay diabetic angiopathy In 2004 an editorial article on the so-called “aspirin resistance” and diabetic angiopathy as related to platelet turnover was published by one of us. An update of this issue is now presented. The evidence of an incomplete inhibition of platelet function by aspirin, despite doses of the drug proved to be clinically effective are employed, was first reported in the ‘80s, in studies devoted to platelet turnover. Based on this concept, the possibility of monitoring the entry of newly formed platelets into the circulation after aspirin ingestion was documented by measuring the return of thromboxane biosynthesis by platelets challenged in vitro by pairs of aggregating agents. The data obtained showed that platelets with intact cyclo- oxygenase activity could be detected into the circulation of control individuals as early as 4–6 hrs after aspirin ingestion, but at shorter time intervals in diabetic angiopathy. In the latter setting, it was concluded that “schedules of aspirin which may suffice in normals are not effective in patients with diabetic angiopathy, pre- sumably because these patients have a high rate of entry of new platelets into the circulation”. As many as 25 years after its original publication, the clinical relevance of an accelerated platelet turnover as to “aspirin resistance” has been confirmed and extended to other clinical settings at high risk of ischemic events. Newer aspirin dosing and scheduling, tailored at reducing the individual patient risk related to an in- complete inhibition of platelet function by a standard aspirin dose should now be defined. © 2011 Elsevier Ltd. All rights reserved. Contents Historical Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 Platelet turnover and aspirin resistance: a fresh insight into the risk of ischemia in diabetes mellitus . . . . . . . . . . . . . . . . . . . . . . 342 Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343 Historical Background Human platelet concentrates stored at 22 °C for transfusion pur- poses, although functionally useful in vivo, progressively lose their ag- gregation potential in vitro in response to high concentrations of aggregating agents employed singly. In contrast, they retain full ag- gregation potential and thromboxane biosynthesis in response to low concentrations of aggregating agents in combination [1]. When this was documented in the early 1980s, the philosophy behind was that, rather than in response to high concentrations of single agents, platelet activation in vivo is likely to occur in response to low concentrations of combinations of aggregating agents [2]. As a matter of fact, the synergistic effects of aggregating agents (e.g. epinephrine and collagen) had also been documented both in vitro in mouse plate- lets (rodents are indeed very resistant to thrombosis and their plate- lets do not aggregate in vitro in response to epinephrine employed alone), and in vivo (mice died from thrombosis following a tail vein injection of 150 μg of collagen plus 1.8 μg of epinephrine) [3]. Of note, aspirin protected mice from the thrombotic challenge, in that model system. Based on data achieved on stored human platelet concentrates as well as in mice, the possibility of monitoring the return of thrombox- ane biosynthesis after aspirin ingestion as an index of the entry of new platelets into the circulation (i.e., the platelet turnover) in platelet-rich plasma (PRP) challenged in vitro by low concentrations of combinations of agents was measured [4]. In course of that study, Thrombosis Research 129 (2012) 341–344 ⁎ Corresponding author at: Dipartimento di Medicina Clinica e Sperimentale, AOU Policlinico “FEDERICO II”, Via S. Pansini 5, 80131 Napoli. Tel./fax: +39 081 7462060. E-mail address: dario.diminno@hotmail.it (M.N.D. Di Minno). 0049-3848/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2011.11.020 Contents lists available at SciVerse ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres