Bleeding tendency in dual antiplatelet therapy with aspirin/clopidogrel: rescue of the template bleeding time in a singl
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ORIGINAL CLINICAL INVESTIGATION
Open Access
Bleeding tendency in dual antiplatelet therapy with aspirin/clopidogrel: rescue of the template bleeding time in a single-center prospective study Raul Altman1*, Ana J Rivas1 and Claudio D Gonzalez2,3
Abstract Background: Patients with heightened platelet reactivity in response to antiplatelet agents are at an increased risk of recurrent ischemic events. However, there is a lack of diagnostic criteria for increased response to combined aspirin/clopidogrel therapy. The challenge is to identify patients at risk of bleeding. This study sought to characterize bleeding tendency in patients treated with aspirin and clopidogrel. Patients/methods: In a single-center prospective study, 100 patients under long-term aspirin/clopidogrel treatment, the effect of therapy was assayed by template bleeding time (BT) and the inhibition of platelet aggregation (IPA) by light transmission aggregometry (LTA). Arachidonic acid (0.625 mmol/L) and adenosine diphosphate (ADP; 2, 4, and 8 μmol/L) were used as platelet agonists. Results: Bleeding episodes (28 nuisance, 2 hematuria [1 severe], 1 severe proctorrhagia, 1 severe epistaxis) were significantly more frequent in patients with longer BT. Template BT ≥ 24 min was associated with bleeding episodes (28 of 32). Risk of bleeding increased 17.4% for each 1 min increase in BT. Correlation was found between BT and IPAmax in response to ADP 2 μmol/L but not to ADP 4 or 8 μmol/L. Conclusion: In patients treated with dual aspirin/clopidogrel therapy, nuisance and internal bleeding were significantly associated with template BT and with IPAmax in response to ADP 2 μmol/L but not in response to ADP 4 μmol/L or 8 μmol/L. Keywords: nuisance bleeding, bleeding time, platelet, inhibition of platelet aggregation, IPA
Introduction Until recently, long-term antiplatelet therapy for the prevention of atherothrombotic disease was limited to aspirin (ASA). The availability of thienopyridines, particularly clopidogrel (CLOP), represented an important addition to the physician’s armamentarium. The combination of CLOP and ASA in patients with acute coronary syndrome (ACS) reduces the risk of reinfarction, stroke, and death by 20% compared with ASA alone [1]. Nevertheless, the current therapy options for these patients are suboptimal. Despite the use of available antiplatelet therapies, the recurrence of ischemic events in patients * Correspondence: [email protected] 1 Centro de Trombosis de Buenos Aires, Buenos Aires, Argentina Full list of author information is available at the end of the article
with ACS is still increasing and bleeding remains an important, and often underappreciated, risk with these therapies. Patient noncompliance because of bleeding contributes to thrombosis events. The exact mechanism of benefit has not yet been elucidated but is clearly related not just to inhibition of platelet aggregation (IPA) but also to modification of the many consequences of the platelet activation-endothelial relationships [2]. The current gold standard for
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