K. Aoshima et al., Treatment of disseminated intravascular coagulation (DIC) with all-trans retinoic acid in an endotoxin-induced rat model, SEM THROMB, 24(3), 1998, pp. 227-231
Anticoagulant drugs such as heparin are often administered to patients with
disseminated intravascular coagulation (DIC) who are also being treated fo
r their underlying disease. The pathophysiology of DIC is so varied that tr
eatment with medications other than anticoagulants may be useful. All-trans
retinoic acid (ATRA), which is used for the treatment of acute promyelocyt
ic leukemia (APL), improves DIC in APL. In vitro studies have reported that
ATRA caused downregulation of tissue factor and upregulation of thrombomod
ulin (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 Wis
tar 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 end
otoxin. ATRA improved the increase in thrombin-antithrombin III (TAT) compl
ex and D-dimer in this model. Fibrin deposition in renal glomeruli was inhi
bited by ATRA administration, with an increase in the intensity of immunohi
stochemical TM staining. These findings suggest that ATRA has beneficial ef
fects in the endotoxin-induced rat DIC model. The mechanism may be an upreg
ulation of TM expression on endothelial cells.