A simulated post-angioplasty low molecular weight heparin schedule in a non-human primate model

Due to a variety of pathophysiologic processes the long-term success rate of percutaneous transluminal angioplasty (PTCA) is only 50-70%. Acute restenosis also occurs in 30-40% of patients. Currently, studies are in progress to investigate the influence of low molecular weight heparin (LMWH) prophylaxis on the patency rate after PTCA. Our aim was to determine an optimal schedule to start the LMWH prophylaxis after the routinely performed heparinization. The alterations of the hemostatic parameters during the drug regimen change-over were evaluated. Non-human primates (Macaca mulatta) were divided into 6 treatment groups (n = 3/group). Three groups received heparin i.v. at 15 U/kg to mimic the end phase of therapeutic treatment infusion given 12-24 hrs. after PTCA. Three groups received full heparinization (250 U/kg i.v.) to mimic patients without the above interim phase therapy. Following both regimens, LMWH (Mono-Embolex) (1 mg/kg s.c.) was started at various intervals. The group initially treated with 15 U/kg heparin exhibited a continued anticoagulant effect when LMWH was started 30 min. after the heparin injection. Whereas, when LMWH was started after 2 hrs. the measurable anticoagulant effect was lost during 1 and 3 hrs. after the heparin injection. When LMWH was started 2 or 4 hrs. after the 250 U/kg dose, the anticoagulant response was sustained. Aside from the anti-IIa and the anti-Xa activity, there was no significant difference in other coagulation parameters between these two regimens. The fibrinolytic system was not altered in the therapeutic heparinization group. However, after the initial bolus of 250 mg/kg heparin, the monkeys treated with LMWH exhibited higher t-PA and D-dimer levels. Although our data shows definite differences between the two drug treatment schedules, further studies are warranted before an optimal drug regimen can be suggested for clinical use.