Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin.
Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia characterized by the proliferation of blasts with distinct morphology, a specific balanced reciprocal translocation t(15;17), and life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL, although hemorrhage-related death during the early phase of therapy remains a serious problem. Moreover, population-based studies have shown that the incidence of early death during induction chemotherapy is nearly 30 %, and the most common cause of death is associated with hemorrhage. Thus, development of a novel treatment strategy to alleviate abnormal coagulation in APL patients is urgently required. Recombinant human soluble thrombomodulin (rTM) comprises the active extracellular domain of TM, and has been used for treatment of DIC since 2008 in Japan. Use of rTM in combination with remission induction chemotherapy, including ATRA, produces potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL. This review article discusses the pathogenesis and features of DIC caused by APL, as well as the possible anticoagulant and anti-leukemic action of rTM in APL patients.
Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Kochi, 783-8505, Japan, ikezoet@kochi-u.ac.jp.
Takayuki
T
Ikezoe
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications*; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use*; D018180:Thrombomodulin / Q000737:chemistry / Q000627:therapeutic use*
D000925:Anticoagulants; D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin