Effect of pyridostigmine (Mestinon) on human platelet aggregation

Normal platelet functions are critical for achieving primary haemostasis. Numerous medications have been shown to affect platelet functions. Pyridostigmine (Mestinon), an orally active cholinesterase inhibitor that is commonly used to treat myasthenia gravis has been documented to cause epistaxis and prolonged bleeding after a cut in anectodal reports. This study was initiated after a patient diagnosed to have myasthenia gravis, developed multiple bruises a week after being started on Mestinon. The objective of this study was to investigate the effect of Mestinon on platelet aggregation stimulated with various agonists in vitro.

A stock solution of Mestinon was prepared by dissolving Mestinon tablet in normal saline. A serial dilution of Mestinon solutions was then prepared from this stock solution. Fresh whole blood from a normal healthy individual was added to this series of diluted Mestinon solutions. These samples were then tested for platelet aggregation using Chrono-log platelet impedance aggregometer with various platelet agonists. Mestinon-free whole blood sample was used for control. The patient's whole blood sample taken at the time of bruises was also tested for platelet aggregation using the same method.

The results showed that in the presence of pyridostigmine (Mestinon), platelet aggregation was inhibited in response to ADP and collagen stimulations. However, when agonists such as ristocetin and arachidonic acid were used, aggregation of platelets was detectable even though the degree of aggregation was relatively reduced when compared with control samples. This pattern of anti-platelet aggregation was also seen in the patient sample.

Pyridostigmine interferes with human platelet aggregation and uncommonly in susceptible patient may result in bleeding tendency. Thus, healthcare workers need to be aware of this uncommon side effect of pyridostigmine.