All-trans retinoic acid is partially effective against lipopolysaccharide-induced but not against tissue-factor-induced disseminated intravascular coagulation in rat models

All-trans retinoic acid (ATRA) has been introduced to the management of acu te promyelocytic leukemia (APL) as a differentiation treatment. This drug n ot only causes complete remission, but also improves disseminated intravasc ular coagulation (DIC) without adding anticoagulants in APL. We have attemp ted to determine whether ATRA is effective against DIC in rat models induce d by tissue factor (TF) or lipopolysaccharide (LPS), because the anticoagul ant effect of ATRA has been considered to induce thrombomodulin upregulatio n and TF downregulation on endothelial cells as well as on APL cells. In ma le Wistar rats, DIC was induced by a 4-h infusion of thromboplastin (3.75 U /kg) or lipopolysaccharide (30 mg/kg). The rats were given ATRA orally each day at a dose of 100 mg/kg per day for 1 week before the injection of TF o r LI'S in ATRA treatment groups, or given low molecular weight heparin (LMW H) 10 min before the injection of TF or LPS (200 U/kg, bolus intravenously) in LMWH treatment groups. No significant changes in hemostatic parameters or markers of organ dysfunction were caused by the ATRA administration, whi le DIC was significantly improved by LMWH in the TF-induced model. DIC was significantly improved by both ATRA and LMWH in the LPS-induced model. Thes e findings suggested that ATRA was useful for treating DIC only in the LPS- induced model, and that drug efficacy should be carefully assessed because the agents used to induce DIC considerably influenced the outcome. (C) 2001 Lippincott Williams & Wilkins.