miR-19a-3p downregulates tissue factor and functions as a potential therapeutic target for sepsis-induced disseminated intravascular coagulation

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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Pathophysiology of disseminated intravascular coagulation (DIC) progresses at a different rate in tissue factor-induced and lipopolysaccharide-induced DIC models in rats

Blood Coagulation & Fibrinolysis ◽

10.1097/01.mbc.0000061290.28953.57 ◽

2003 ◽

Vol 14 (3) ◽

pp. 221-228 ◽

Cited By ~ 27

Author(s):

Hidesaku Asakura ◽

Yukio Suga ◽

Tomotaka Yoshida ◽

Yasuo Ontachi ◽

Tomoe Mizutani ◽

...

Keyword(s):

Tissue Factor ◽

Disseminated Intravascular Coagulation ◽

Intravascular Coagulation

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Measuring tissue factor (factor III) activity in plasma.

Clinical Chemistry ◽

10.1093/clinchem/35.9.1897 ◽

1989 ◽

Vol 35 (9) ◽

pp. 1897-1900 ◽

Cited By ~ 27

Author(s):

C Fukuda ◽

K Iijima ◽

K Nakamura

Keyword(s):

Tissue Factor ◽

Disseminated Intravascular Coagulation ◽

Coagulation Factors ◽

High Plasma ◽

Mean Value ◽

Chromogenic Substrate ◽

Intravascular Coagulation ◽

Endogenous Inhibitors ◽

Tissue Thromboplastin ◽

The Mean

Abstract This is a method for measuring tissue factor (TF, Factor III, tissue thromboplastin) activity in plasma by using a chromogenic substrate. As pretreatment, the euglobulin fraction of plasma was prepared by removing endogenous inhibitors and heated at 60 degrees C for 3 min to remove fibrinogen. This allowed us to measure the low TF activity in plasma that could not otherwise be measured. Neither phospholipids nor coagulation factors VII, IX, X, or Xa in the samples interfere. Within-run and day-to-day reproducibility were both good. The mean value obtained by this method for normal persons was 1.02 (SD 0.91) arbitrary units/L. A markedly high plasma TF activity of 20 arb. units/L or more was observed in patients with some types of disseminated intravascular coagulation.

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Beneficial effect of JTV-803, a new synthetic inhibitor of activated factor X, against both lipopolysaccharide-induced and tissue factor-induced disseminated intravascular coagulation in rat models

Blood Coagulation & Fibrinolysis ◽

10.1097/00001721-200204000-00009 ◽

2002 ◽

Vol 13 (3) ◽

pp. 233-239 ◽

Cited By ~ 5

Author(s):

H. Asakura ◽

T. Ichino ◽

T. Yoshida ◽

Y. Suga ◽

Y. Ontachi ◽

...

Keyword(s):

Beneficial Effect ◽

Tissue Factor ◽

Disseminated Intravascular Coagulation ◽

Factor X ◽

Rat Models ◽

Intravascular Coagulation ◽

Synthetic Inhibitor

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Microparticle-associated tissue factor activity in dogs with disseminated intravascular coagulation

Journal of Veterinary Medical Science ◽

10.1292/jvms.19-0553 ◽

2020 ◽

Vol 82 (1) ◽

pp. 56-60

Author(s):

Kosuke KOBAYASHI ◽

Kenji BABA ◽

Masaya IGASE ◽

Takako Shimokawa MIYAMA ◽

Satoshi KAMBAYASHI ◽

...

Keyword(s):

Tissue Factor ◽

Disseminated Intravascular Coagulation ◽

Factor Activity ◽

Intravascular Coagulation ◽

Tissue Factor Activity

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Significant Correlations between Tissue Factor and Thrombin Markers in Trauma and Septic Patients with Disseminated Intravascular Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615025 ◽

1998 ◽

Vol 79 (06) ◽

pp. 1111-1115 ◽

Cited By ~ 96

Author(s):

Satoshi Nanzaki ◽

Shigeyuki Sasaki ◽

Osamu Kemmotsu ◽

Satoshi Gando

Keyword(s):

Tissue Factor ◽

Disseminated Intravascular Coagulation ◽

Thrombin Generation ◽

Trauma Patients ◽

Elevated Plasma ◽

Antigen Concentration ◽

Intravascular Coagulation ◽

Factor Antigen ◽

D Dimer

SummaryTo determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 ± 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.

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