Clinical Features and Treatment Outcomes of Six Patients with Disseminated Intravascular Coagulation Resulting from Acute Promyelocytic Leukemia and Treated with Recombinant Human Soluble Thrombomodulin at a Single Institution

OBJECTIVE: Acute promyelocytic leukemia (APL) is characterized by the proliferation of blasts with distinct morphology and promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) transcripts. Although the treatment outcome is dramatically improved by all-trans retinoic acid (ATRA), life-threatening bleeding from enhanced fibrinolytic-type disseminated intravascular coagulation (DIC) remains a serious clinical problem, and a standard treatment has not been established. However, recent reports indicate that recombinant human soluble thrombomodulin (rTM) is effective against DIC. METHODS: To elucidate the clinical characteristics and outcomes of DIC resulting from APL, we retrospectively analyzed 10 patients with DIC resulting from APL at our institution over a six year period. Of the 10 patients, four were treated with serine protease inhibitors (SPI) and six were treated with rTM. The diagnosis of DIC was based on the diagnostic criteria of the Japanese Ministry of Health and Welfare. In addition to treating APL with ATRA, rTM was administered for six consecutive days. RESULTS: The DIC was resolved within seven days after initiating treatment in 25.0% (1/4) of the patients in the SPI group and 66.6% (4/6) of the patients in the rTM group. Although the rTM group consisted of patients with life-threatening bleeding who required RCC transfusion, a prompt resolution rate and reduced DIC score without progression of bleeding was achieved in this group. All patients were alive after the 28-day observation period. CONCLUSION: Based on the present findings, rTM administration may be an effective, safe, and feasible therapeutic modality, producing a rapid resolution without progression of hemorrahage.