Effects of recombinant human soluble thrombomodulin and danaparoid sodium for sepsis-induced disseminated intravascular coagulation

2012 ◽  
Vol 19 (4) ◽  
pp. 603-608 ◽  
Author(s):  
Takeshi Umegaki ◽  
Kenichiro Nishi ◽  
Kiyohiko Hatano ◽  
Akihisa Okamoto ◽  
Nobuyuki Hamano ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Danaparoid Sodium ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
Recombinant Human Soluble Thrombomodulin

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

scholarly journals Associations Among Coagulation-Related Variables, Resolution of Disseminated Intravascular Coagulation (DIC), and Mortality in Patients with Sepsis-Induced DIC Treated with Recombinant Human Soluble Thrombomodulin: A Retrospective Observational Study

2021 ◽  
Author(s):  
Chieko Mitaka ◽  
Izumi Kawagoe ◽  
Daizoh Satoh ◽  
Masakazu Hayashida
Keyword(s):  
Platelet Count ◽  
Observational Study ◽  
Disseminated Intravascular Coagulation ◽  
Early Phase ◽  
Degradation Products ◽  
International Normalized Ratio ◽  
Soluble Thrombomodulin ◽  
Intravascular Coagulation ◽  
Before And After ◽  
Recombinant Human Soluble Thrombomodulin

Abstract Background: We evaluated associations among coagulation-related variables, resolution of disseminated intravascular coagulation (DIC), and mortality in patients with sepsis-induced DIC treated with recombinant human soluble thrombomodulin (rTM). Methods: We retrospectively investigated patients with sepsis-induced DIC treated with rTM. Changes in coagulation-related variables before and after treatment with rTM were examined. Further, associations between coagulation-related variables and DIC resolution were evaluated. Results: A total of 123 patients were included. The platelet count, prothrombin international normalized ratio (PT-INR), and fibrin/fibrinogen degradation products (FDP) significantly (p < 0.001) improved after rTM administration in survivors (n = 98), but not in nonsurvivors (n = 25). However, the DIC score significantly (p < 0.001) reduced not only in survivors but also in nonsurvivors. PT-INR before rTM was significantly (p = 0.0029) lower in patients attaining than not attaining DIC resolution (n = 87 and 36, respectively). The 28-day mortality was significantly lower in patients attaining than not attaining DIC resolution (11.5% vs. 41.7 %, p = 0.0001).Conclusions: The DIC score significantly reduced after rTM in both survivors and nonsurvivors. rTM might play an important role in improving DIC, especially when treatment with rTM is initiated in the early phase of DIC.

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