Importance of timing of antiaggregant treatment in the prevention of radiation induced enteropathy

Chronic radiation enteropathy (CRE) is an undesirable radiation-induced toxicity and a common health problem in patients with pelvic or abdominal malignancies. Damage to microvascular endothelial cells and connective tissue is blamed to cause this adverse effect. It is shown that platelets are the first cellular elements that initiate the homeostatic and inflammatory responses and release of several proinflammatory and fibrinogenic mediators. Antiplatelet agents such as ticlopidine and clopidogrel were shown to prevent CRE and this effect is believed to be directed by their activities against thrombocytes. However, recent studies have shown that these drugs also induce apoptosis in endothelial cells and may lead to decreased expression of endothelial prostacyclin and thrombomodulin (TM) and increased release of von Willebrand factor which are shown to be major contributors of coagulation process. Assuming that radiation induced apoptosis occur 6-10 h after irradiation, we think that timing of these antiaggregant drugs with irradiation is important and a 6-10 h interval between these may be beneficial to avoid this adverse interaction.