A Retrospective Observational Study on the Administration Duration of Recombinant Human Soluble Thrombomodulin in Patients with Infection-induced Disseminated Intravascular Coagulation

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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Effect of Recombinant Human Soluble Thrombomodulin on Coagulation-Related Variables in Patients With Sepsis-Induced Disseminated Intravascular Coagulation: A Retrospective Observational Study

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211050356 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110503

Author(s):

Chieko Mitaka ◽

Izumi Kawagoe ◽

Daizoh Satoh ◽

Masakazu Hayashida

Keyword(s):

Platelet Count ◽

Observational Study ◽

Disseminated Intravascular Coagulation ◽

Degradation Products ◽

International Normalized Ratio ◽

Fibrinogen Degradation Products ◽

Soluble Thrombomodulin ◽

Intravascular Coagulation ◽

Before And After ◽

Recombinant Human Soluble Thrombomodulin

To evaluate associations among coagulation-related variables, resolution of disseminated intravascular coagulation (DIC) and mortality, we retrospectively investigated 123 patients with sepsis-induced DIC treated with recombinant human soluble thrombomodulin (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. The platelet count, prothrombin international normalized ratio (PT-INR), and fibrin/fibrinogen degradation products (FDP) significantly ( p < .001) improved after rTM administration in survivors (n = 98), but not in nonsurvivors (n = 25). However, the DIC score significantly ( p < .001) reduced in survivors and in nonsurvivors. Among coagulation-related variables examined before rTM, only PT-INR was significantly ( p = .0395) lower in survivors than in nonsurvivors, and PT-INR before rTM was significantly ( p = .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 = .0001). In conclusion, the initiation of rTM administration before marked PT-INR elevation may be important to induce DIC resolution and thus to decrease mortality in patients with sepsis-induced DIC. Conversely, the treatment with rTM in patients with marked PT-INR elevation may be not so effective in achieving such goals.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648448 ◽

1992 ◽

Vol 67 (03) ◽

pp. 366-370 ◽

Cited By ~ 16

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.

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