Effects of Ticlopidine, a new platelet function suppressing drug in patients with prosthetic heart valves

Abstract

The effect of ticlopidine (fig. 1), a new platelet aggregation inhibitor, was studied in 15 patients with Björk-Shiley prosthetic heart valves (6 aortic, 6 mitral, 3 aortic and mitral). The patients were 9 men and 6 women, aged 22 to 55 years old, who had had valve prostheses placed 2 to 43 months (mean 23.7 months) prior to entry into the study. They received 200mg of ticlopidine, divided into two oral doses, daily, and were followed up for more than 3 months. Platelet adhesiveness and aggregation were examined 1, 2, and 4 weeks, and 3 months after the treatment, and the values were compared to those obtained before the treatment. Platelet adhesiveness was determined by a modified technique of Salzman. A Sienco dual sample aggregation meter was used to measure changes of platelet aggregation through light transmission of citrated platelet-rich plasma to which adenosine diphosphate (ADP) had been added. The platelet count of the plasma sample was adjusted to a range of 250-350, 000/mm3. Student's paired t-test was used for statistical significance.Platelet adhesiveness decreased significantly at 1 week, 2 weeks, and 3 months after the treatment, but no significant change was found at 4 weeks (fig. 2).In every patient, platelet aggregation induced by 4μM ADP (final concentration) showed an obvious reduction one week after the treatment, and this effect continued for more than 3 months (fig. 3). A similar reduction in the aggregation caused by 20μM ADP (final concentration) was observed. In many cases, the aggregation caused by 20μM ADP, which showed the second phase of aggregation, changed after the treatment to show only the first phase of aggregation (fig. 4). Ticlopidine inhibited both the first and the second phase of ADP-induced aggregation. This dosage seemed to cause a reduction in platelet aggregation about 3 days after the start of the treatment.We did not observe any interaction between ticlopidine and warfarin in this study.None of the patients had clinical symptoms or side effects due to ticlopidine and no episodes of thromboembolism occurred during the examination period. Bleeding time increased slightly at 4 weeks after the treatment. No abnormal alteration was observed in the white blood cell counts, coagulation time, fibrinogen level, fasting blood sugar, serum electrolites, total protein, hepatic and renal function tests at 4 weeks and 3 months after the treatment.Ticlopidine seems to be a useful platelet function suppressing drug for patients with prosthetic heart valves.