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.
