Treatment of Disseminated Intravascular Coagulation (DIC) with All-trans Retinoic Acid in an Endotoxin-Induced Rat Model

Abstract

Anticoagulant drugs such as heparin are often administered to patients with disseminated intravascular coagulation (DIC) who are also being treated for their underlying disease. The pathophysiology of DIC is so varied that treatment with medications other than anticoagulants may be useful. All-trans retinoic acid (ATRA), which is used for the treatment of acute promyelocytic leukemia (APL), improves DIC in APL. In vitro studies have reported that ATRA caused downregulation of tissue factor and upregulation of thrombomodulin (TM) on endothelial cells as well as APL cells. We examined the effect of ATRA in an endotoxin-induced rat DIC model. DIC was induced in male Wistar rats with a 4-h sustained infusion of endotoxin at a dose of 30 mg/kg. ATRA (20 mg/day) was given every day for 1 week before the injection of endotoxin. ATRA improved the increase in thrombin-antithrombin III (TAT) complex and D-dimer in this model. Fibrin deposition in renal glomeruli was inhibited by ATRA administration, with an increase in the intensity of immunohistochemical TM staining. These findings suggest that ATRA has beneficial effects in the endotoxin-induced rat DIC model. The mechanism may be an upregulation of TM expression on endothelial cells.

Keywords:

All-trans retinoic acid (ATRA) - disseminated intravascular coagulation (DIC) - endotoxin - thrombomodulin