scholarly journals The effect of activated protein C in the experimental disseminated intravascular coagulation model formed by lipopolysaccharide infusion

2020 ◽  
Vol 35 (11) ◽  
Author(s):  
Abdullah Şahin ◽  
Nazmi Özer
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
Activated Protein C ◽  
Intravascular Coagulation

The Leiden Mutation and Activated Protein C Resistance as Risk Factors for Disseminated Intravascular Coagulation in Acutely Poisoned Patients

2006 ◽  
Vol 44 (1) ◽  
pp. 53-57
Author(s):  
Mirosław Prazanowski ◽  
Barbara Kur ◽  
Małgorzata Barańska ◽  
Waldemar Lutz ◽  
Bożena Piłacik ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
Activated Protein C ◽  
Activated Protein C Resistance ◽  
Intravascular Coagulation

Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C–deficient mice

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4823-4827 ◽  
Author(s):  
Marcel Levi ◽  
Janine Dörffler-Melly ◽  
Pieter Reitsma ◽  
Harry Büller ◽  
Sandrine Florquin ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
Activated Protein C ◽  
Intravascular Coagulation ◽  
Cytokine Activation ◽  
Tnf Α ◽  
Single Allele ◽  
Factor Α ◽  
Heterozygous Deficiency

Abstract In the pathogenesis of sepsis and disseminated intravascular coagulation (DIC), dysfunctional anticoagulant pathways are important. The function of the protein C system in DIC is impaired because of low levels of protein C and down-regulation of thrombomodulin. The administration of (activated) protein C results in an improved outcome in experimental and clinical studies of DIC. It is unknown whether congenital deficiencies in the protein C system are associated with more severe DIC. The aim of the present study was to investigate the effect of a heterozygous deficiency of protein C on experimental DIC in mice. Mice with single-allele targeted disruption of the protein C gene (PC+/–) mice and wild-type littermates (PC+/+) were injected with Escherichia coli endotoxin (50 mg/kg) intraperitoneally. PC+/–mice had more severe DIC, as evidenced by a greater decrease in fibrinogen level and a larger drop in platelet count. Histologic examination showed more fibrin deposition in lungs, kidneys, and liver in mice with a heterozygous deficiency of protein C. Interestingly, PC+/– mice had significantly higher levels of proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, indicating an interaction between the protein C system and the inflammatory response. Survival was lower at 12 and 24 hours after endotoxin in the PC+/– mice. These results confirm the important role of the protein C system in the coagulative-inflammatory response on endotoxemia and may suggest that congenital deficiencies in the protein C system are associated with more severe DIC and adverse outcome in sepsis.

Recombinant Thrombomodulin and Activated Protein C in the Treatment of Disseminated Intravascular Coagulation

1999 ◽  
Vol 82 (08) ◽  
pp. 718-721 ◽  
Author(s):  
Ikuro Maruyama
Keyword(s):  
Endothelial Cells ◽  
Tissue Factor ◽  
Blood Coagulation ◽  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
Activated Protein C ◽  
Coagulation Cascade ◽  
Regulation System ◽  
Luminal Surface ◽  
Intravascular Coagulation

IntroductionThe blood coagulation cascade is regulated by the luminal surface of the endothelial cell lining.1 Endothelial cells synthesize tissue factor pathway inhibitor (TFPI), which, in part, binds to the cell surface glycosaminoglycans and inhibits factors Xa, VIIa, and tissue factor.2 Endothelial cells also produce and exhibit thrombomodulin (TM) on their luminal surface.3 TM is a kind of thrombin receptor that forms a 1:1 complex with thrombin. In this complex, thrombin activates protein C (PC) more than 1,000-fold more than thrombin alone. TM then loses its procoagulant activities, which include fibrinogen clotting, activation of factors V and VIII, and platelet activation. Thus, TM converts thrombin from a procoagulant protease to an anticoagulant. Pathologic states, such as an endothelial injury or perturbation or continuous rapid coagulation cascade activation, overcomes the endothelial regulating activity, resulting in the development of intravascular coagulation and the induction of disseminated intravascular coagulation (DIC). Theoretically, then, supplementing soluble TM or activated PC (APC) to reconstitute the endothelial coagulation regulation system in the circulation and regulate pathologically-activated blood coagulation could be beneficial. In this chapter, application of soluble TM and APC in the treatment of DIC is reviewed.

scholarly journals Activation and complexation of protein C and cleavage and decrease of protein S in plasma of patients with intravascular coagulation

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 455-461 ◽  
Author(s):  
MJ Heeb ◽  
D Mosher ◽  
JH Griffin
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Coagulation Test ◽  
Major Band ◽  
Intravascular Coagulation ◽  
Protein C Inhibitor ◽  
Dependent Protein

Abstract Activated protein C (APC) is inhibited by two major plasma inhibitors (PCIs). To find evidence for in vivo complexation of APC, immunoblotting studies were performed on plasmas of 85 patients with suspected disseminated intravascular coagulation (DIC). Samples from 62 of these patients contained 5% to 35% of protein C antigen in APC:inhibitor complexes, indicating that protein C activation and inhibition had occurred. In 24 normal plasmas, no detectable APC:PCI complexes were observed (less than 5%). Patients with higher levels of complexes had more abnormal coagulation test data for DIC. The major band of APC complexes detected by anti-protein C antibodies did not react with antibodies to the heparin-dependent protein C inhibitor (PCI- 1) previously described. Rather, APC was complexed with another recently described plasma protein C inhibitor, PCI-2. Immunoblotting studies for protein S, the cofactor for APC, revealed that the majority of the DIC patient plasmas contained a higher than normal proportion of protein S in cleaved form, suggesting that protein S may have been proteolytically inactivated. Protein S total antigen levels were also found to be low in DIC patients, excluding those with malignancy. These studies support the hypothesis that the protein C pathway is activated during DIC.

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