title: Rapid improvement of coagulopathy by all-trans retinoic acid in acute promyelocytic leukemia.
abstract: Treatment of acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA) was associated with rapid improvement in hemostatic markers. We made serial analyses of various hemostatic parameters in seven newly diagnosed APL patients. In all patients at diagnosis, plasma fibrinogen/fibrin degradation product (fragment-E), cross-linked fibrin degradation product (D-dimer fragment), thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex were elevated, indicating the presence of disseminated intravascular coagulation (DIC). Antithrombin III (ATIII) levels were normal in all patients except for the patient with congenital ATIII deficiency. In four patients subsequently treated with ATRA without anticoagulant therapy, these hemostatic markers returned to near-normal levels by day 7 of treatment, indicating that DIC was essentially resolved. By contrast, in three patients who received conventional chemotherapy with a continuous low-dose heparin, improvement of coagulopathy was slower than in patients treated with ATRA. These results suggest that ATRA therapy exerts the rapid improvement in abnormal hemostatic markers in APL patients without any anticoagulant therapies, by inducing differentiation of leukemic cells and, in turns no massive release of procoagulant or fibrinolytic substances from these cells.
authors.affiliation: Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawai
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Kizaki
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: T
authors.initials: T
authors.lastname: Kamata
authors.forename: H
authors.initials: H
authors.lastname: Uchida
authors.forename: T
authors.initials: T
authors.lastname: Moriki
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: M
authors.initials: M
authors.lastname: Tokuhira
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D001780:Blood Coagulation Tests; D004211:Disseminated Intravascular Coagulation / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006487:Hemostasis; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000150:complications; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D014212:Tretinoin