The effects of chloroquine on bleeding time and disappearance of platelet 5-hydroxytryptamine in rabbits.

Abstract

Chloroquine inhibits platelet aggregation in vitro and in vivo. Because inhibition of platelet aggregation may prolong bleeding time, the effect of chloroquine administration on bleeding time and disappearance of platelet serotonin, which may affect bleeding time, were studied. Platelets were harvested from 12 rabbits. They were labelled with (111)In to tag individual platelets and (14)C-labelled 5-hydroxytryptamine (5HT) or serotonin. Doubly labelled platelets from the rabbits were returned to their donors. At timed intervals, from 2 to 66 hours, blood samples were drawn and platelets collected. (111)In and (14)C were separately counted. In 6 experiments, the animals served as control and received normal saline intraperitoneally (IP) daily for 4 days; the other 6 rabbits served as test and were given a therapeutic dose of chloroquine phosphate (10 mg/kg, IP) daily for 4 days. Indium disappeared in an exponential fashion in both control and test groups. The fraction of indium disappearing per hour was significantly less in chloroquine-treated rabbits than in control rabbits (P <.001). Ninety-nine percent of the indium-labelled platelets disappeared in 7.0 days in chloroquine-treated rabbits and 5.8 days in control rabbits (P <.001). Bleeding times in chloroquine-treated and control rabbits were not significantly different (64.8 +/- 2.2 vs. 62.3 +/- 4.0 sec, respectively). However, the labelled platelet serotonin disappeared more slowly in chloroquine-treated rabbits than in control rabbits. (K for chloroquine-treated and control rabbits was 0.0096 +/- 0.0064 and 0. 0254 +/- 0.0016; respectively, P <.001). Chloroquine prolongs platelet survival but does not affect bleeding time in rabbits. Chloroquine also slows down the disappearance of labelled platelet serotonin. We propose that chloroquine increases the recycling of platelet 5HT, passing it on from platelet to platelet in rabbits and this may have a role in the maintenance of hemostasis.