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Thromb Haemost 1991; 65(05): 504-510
DOI: 10.1055/s-0038-1648180
Original Article
Schattauer GmbH Stuttgart

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

Authors

  • Raffaele De Caterina

    The Laboratory for Thrombosis and Vascular Research, C.N.R. Institute of Clinical Physiology, Pisa, Italy

  • Rosa Sicari

    The Laboratory for Thrombosis and Vascular Research, C.N.R. Institute of Clinical Physiology, Pisa, Italy

  • Walter Bernini

    The Laboratory for Thrombosis and Vascular Research, C.N.R. Institute of Clinical Physiology, Pisa, Italy

  • Guido Lazzerini

    The Laboratory for Thrombosis and Vascular Research, C.N.R. Institute of Clinical Physiology, Pisa, Italy

  • Giuliana Buti Strata

    The Laboratory for Thrombosis and Vascular Research, C.N.R. Institute of Clinical Physiology, Pisa, Italy

  • Daniela Giannessi

    The Laboratory for Thrombosis and Vascular Research, C.N.R. Institute of Clinical Physiology, Pisa, Italy
Further Information

Publication History

Received 16 October 1990

Accepted after revision 18 January 1991

Publication Date:
24 July 2018 (online)

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Summary

Ticlopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.