title: Recombinant human soluble thrombomodulin and mortality in sepsis-induced disseminated intravascular coagulation. A multicentre retrospective study.
abstract: Recombinant human soluble thrombomodulin (rhTM) is a novel class of anticoagulants for treating disseminated intravascular coagulation (DIC). Although rhTM is widely used in clinical settings throughout Japan, there is limited clinical evidence supporting the use of rhTM in patients with sepsis-induced DIC. Furthermore, rhTM is not approved for DIC treatment in other countries. This study aimed to clarify the survival benefits of rhTM administration in critically ill patients. Data from 3,195 consecutive adult patients who were admitted to 42 intensive care units for the treatment of severe sepsis or septic shock between January 2011 and December 2013 were retrospectively analysed, and 1,784 patients were diagnosed with DIC based on the scoring algorithm from the Japanese Association for Acute Medicine DIC (n = 645, rhTM group; n = 1,139, control group). Propensity score matching created 452 matched pairs, and logistic regression analysis revealed a significant association between rhTM administration and lower in-hospital all-cause mortality in the propensity score-matched groups (odds ratio, 0.757; 95 % confidence interval, 0.574-0.999, p = 0.049). Inverse probability of treatment weighted and quintile-stratified analyses also revealed significant associations between rhTM administration and lower in-hospital all-cause mortality. Survival time in the propensity score-matched rhTM group was significantly longer than that in the propensity score-matched control group (hazard ratio, 0.781; 95 % confidence interval, 0.624-0.977, p = 0.03). Bleeding complications were not more frequent in the rhTM groups. In conclusion, this study demonstrated that rhTM administration is associated with reduced in-hospital all-cause mortality among patients with sepsis-induced DIC.
authors.affiliation: Mineji Hayakawa, MD, PhD, Emergency and Critical Care Center, Hokkaido University Hospital, N14W5 Kita-ku, Sapporo 060-8648, Japan, Tel.: +81 11 706 7377, Fax: +81 11 706 7378, E-mail: mineji@dream.com.
authors.forename: Mineji
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Kazuma
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Saito
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Uchino
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kudo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Sanui
authors.forename: Kohei
authors.initials: K
authors.lastname: Takimoto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Mayumi
authors.forename: Kota
authors.initials: K
authors.lastname: Ono
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D057216:Propensity Score; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D018805:Sepsis / Q000150:complications; D012995:Solubility; D018180:Thrombomodulin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin
keywords: Sepsis; coagulation abnormality; disseminated intravascular coagulation; mortality; thrombomodulin