scholarly journals Recombinant Human Soluble Thrombomodulin Contributes to a Reduction In-Hospital Mortality of Acute Cholangitis with Disseminated Intravascular Coagulation: A Propensity Score Analyses of a Japanese Nationwide Database

2020 ◽  
Vol 252 (1) ◽  
pp. 53-61
Author(s):  
Kunio Tarasawa ◽  
Kenji Fujimori ◽  
Kiyohide Fushimi
Keyword(s):  
Propensity Score ◽  
Hospital Mortality ◽  
Disseminated Intravascular Coagulation ◽  
Acute Cholangitis ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
Nationwide Database ◽  
Recombinant Human Soluble Thrombomodulin

Recombinant human soluble thrombomodulin and mortality in sepsis-induced disseminated intravascular coagulation

2016 ◽  
Vol 115 (06) ◽  
pp. 1157-1166 ◽  
Author(s):  
Kazuma Yamakawa ◽  
Shinjiro Saito ◽  
Shigehiko Uchino ◽  
Daisuke Kudo ◽  
Yusuke Iizuka ◽  
...  
Keyword(s):  
Propensity Score ◽  
Confidence Interval ◽  
Disseminated Intravascular Coagulation ◽  
Bleeding Complications ◽  
Control Group ◽  
Clinical Settings ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
All Cause Mortality ◽  
Recombinant Human Soluble Thrombomodulin

SummaryRecombinant 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.

The Glycosaminoglycan of Recombinant Human Soluble Thrombomodulin Affects Antithrombotic Activity in a Rat Model of Tissue Factor-Induced Disseminated Intravascular Coagulation

1992 ◽  
Vol 67 (03) ◽  
pp. 366-370 ◽  
Author(s):  
Katsuhiko Nawa ◽  
Teru Itani ◽  
Mayumi Ono ◽  
Katsu-ichi Sakano ◽  
Yasumasa Marumoto ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Disseminated Intravascular Coagulation ◽  
Rat Model ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
Platelet Counts ◽  
Recombinant Human Soluble Thrombomodulin

SummaryPrevious studies on recombinant human soluble thrombomodulin (rsTM) from Chinese hamster ovary cells revealed that rsTM was expressed as two proteins that differed functionally in vitro due to the presence (rsTMp) or absence (rsTMa) of chondroitin-4-sulfate. The current study evaluates the in vivo behavior of rsTM in rats and in a rat model of tissue factor-induced disseminated intravascular coagulation (DIC). rsTMp was more potent than rsTMa for prolongation of the activated partial thromboplastin time (APTT) and their in vivo half-lives determined by ELISA were 20 min for rsTMp and 5.0 h for rsTMa. Injection of a tissue factor suspension (5 mg/kg) resulted in DIC as judged by decreased platelet counts and fibrinogen concentrations, prolonged APTT, and increased fibrin and fibrinogen degradation products (FDP) levels. A bolus injection of either rsTM (0.2 mg/kg) 1 min before induction of DIC essentially neutralized effects on platelets, fibrinogen, and FDP levels, and had only a moderate effect on APTT prolongation. The dose of anticoagulant to inhibit the drop in platelet counts by 50% (ED50) was 0.2 mg/kg rsTMa, 0.07 mg/kg rsTMp, and 7 U/ kg heparin. The effect of increasing concentrations of rsTM and heparin on bleeding times were compared in experiments involving incision of the rat tail. Doubling of the bleeding times occurred at 5 mg/kg rsTMa, 3 mg/kg rsTMp or 90 U/kg heparin. These values represent a 25-fold increase over the ED50 for rsTMa, 43-fold for rsTMp and 13-fold for heparin. These results suggest that rsTMp is a potent anticoagulant to inhibit the platelet reduction when injected prior to the induction of DIC in rats.

87. Recombinant human soluble thrombomodulin for obstetric disseminated intravascular coagulation

2018 ◽  
Vol 13 ◽  
pp. S72
Author(s):  
Takuma Yamada ◽  
Taro Fukuda ◽  
Risa Yoshimoto ◽  
Takuji Ueno ◽  
Takehiko Takeda ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
Recombinant Human Soluble Thrombomodulin
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