Recent Change in Treatment of Disseminated Intravascular Coagulation in Japan

Abstract

This study investigated the time trends and hospital factors affecting the use of drugs for infectious disease-associated disseminated intravascular coagulation (DIC) based on a national administrative database. A total of 14 324 patients with infectious disease-associated DIC were referred to 1041 hospitals from 2010 to 2012 in Japan. Patients' data were collected from the administrative database to determine time trends and hospital factors affecting the use of drugs for DIC. Three study periods were established, namely, the fiscal years 2010 (n ¼ 3308), 2011 (n ¼ 5403), and 2012 (n ¼ 5613). The use of antithrombin, heparin, protease inhibitors, and recombinant human soluble thrombomodulin (rhs-TM) for DIC was evaluated. The frequency of use of antithrombin, heparin, and protease inhibitors decreased while that of rhs-TM significantly increased from 2010 to 2012 in Japan (25.1% in 2010, 43.1% in 2011, and 56.8% in 2012; P < .001, respectively). Logistic regression showed that the study period was associated with the use of rhs-TM in patients with DIC. The odds ratio (OR) for 2011 was 2.34 (95% confidence interval [CI], 2.12-2.58; P < .001) whereas that for 2012 was 4.34 (95% CI, 3.94-4.79; P < .001). A large hospital size was the most significant factor associated with the use of rhs-TM in patients with DIC (OR, 3.14; 95% CI, 2.68-3.66; P < .001). The use of rhs-TM has dramatically increased. A large hospital size was significantly associated with the increased use of rhs-TM in patients with DIC from 2010 to 2012 in Japan.

A summary of the Japan septic disseminated intravascular coagulation study

“…Recombinant human soluble thrombomodulin (rhTM), like AT, is frequently used as an anticoagulant for treating DIC 18, 23. Thrombomodulin is a receptor of thrombin and protein C on the endothelial cell surface and plays an important role in the regulation of coagulation and the innate immune system 24.…”

Management of disseminated intravascular coagulation: current insights on antithrombin and thrombomodulin treatments

“… 4 Based on the national administrative database in Japan, Murata et al also reported the use of drugs for sepsis-induced DIC from 2010 to 2012. 11 In both of these studies, antithrombin (AT) and recombinant human soluble thrombomodulin (rhTM) were frequently used for the treatment of sepsis-induced DIC in Japan ( Table 1 ). However, the frequencies of heparin treatment differed greatly between the two studies.…”

“…However, the frequencies of heparin treatment differed greatly between the two studies. 4 , 11 Although the indications for heparin treatment were unclear for patients with sepsis-induced DIC in the study by Murata et al, 11 they were specified in the Japan-Septic DIC study. 4 In the report by Murata et al, heparin treatment was not administered solely for the treatment of sepsis-induced DIC.…”

“…In conclusion, investigators recommended weekly rhTM treatment with moderate quality of evidence after evaluation using the Grading of Evidence, Assessment, Development and Evaluation approach. 47 Although rhTM is being widely used in clinical settings for treatment of DIC in Japan, 4 , 11 rhTM is currently being evaluated by a Phase III international RCT in other countries. 48…”

Effects of combination therapy using antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation

“…Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation (DIC) is widely performed in Japan [ 1 ], and antithrombin concentrate and recombinant thrombomodulin are the two most popular agents utilized for this treatment [ 2 ]. However, not a single anticoagulant has proven to be effective.…”