The Pathophysiology of Disseminated Intravascular Coagulation

1999 ◽  
Vol 82 (08) ◽  
pp. 713-717 ◽  
Author(s):  
Janneke Timmerman ◽  
Marcel Levi ◽  
Hugo ten Cate
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Factor Viia ◽  
Underlying Disease ◽  
Gram Negative Bacteria ◽  
Catalytic Complex ◽  
Gram Negative ◽  
Intravascular Coagulation ◽  
Disease States ◽  
Wide Range ◽  
A Cell

IntroductionDisseminated intravascular coagulation (DIC) can be defined as “an acquired syndrome characterized by the activation of intravascular coagulation up to intravascular fibrin formation. The process may be accompanied by secondary fibrinolysis or inhibited fibrinolysis.”1 Being an acquired disorder, DIC occurs in a wide range of underlying disease states, including sepsis (both by Gram positive and Gram negative bacteria), burns, preeclampsia, malignancy, and polytrauma.1 In the majority of conditions, the pathogenesis of DIC remains only partly understood, an exception is Gram negative septicemia. In the following chapter, we will discuss the presumed mechanism by which DIC is elicited in different pathological states. The initiation of DIC follows the presentation of the glycoprotein tissue factor (TF) at a cellular surface, being either an intact or perturbed cell, or a cell membrane remnant.2 The extracellular TF molecules may interact with circulating factor VIIa to form a catalytic complex. The complex binds the coagulation zymogen factors IX and X. This leads to proteolytic cleavage of these molecules, yielding enzymatically active factors IXa and Xa and promoting the activation of prothrombin to thrombin (Fig. 1).

scholarly journals Endotoxins and Anti-endotoxins (Their Relevance to the Anaesthetist and the Intensive Care Specialist)

1989 ◽  
Vol 17 (1) ◽  
pp. 49-55 ◽  
Author(s):  
J. G. Brock-Utne ◽  
S. L. Gaffin
Keyword(s):  
Intensive Care ◽  
Organ Failure ◽  
Disseminated Intravascular Coagulation ◽  
Systemic Circulation ◽  
Toxic Effects ◽  
Gram Negative Bacteria ◽  
Intestinal Ischaemia ◽  
Gram Negative ◽  
Intravascular Coagulation ◽  
Care Specialist

Endotoxins (lipopolysaccharides, LPS) are potent bacterial poisons always present within the intestines in considerable amounts. Several pathophysiological conditions such as hypovolaemia, hypoxia, intestinal ischaemia, burns and radiation lead to a breakdown in the barrier and depending upon the extent of the injury, endotoxins enter the systemic circulation in increasing amounts. Antibiotics do not inactivate the endotoxins which continue to exert their toxic effects leading to nausea, vomiting, diarrhoea, fever, disseminated intravascular coagulation, vascular collapse and organ failure. When nonabsorbable antibiotics are given prior to the insult, systemic endotoxaemia is prevented. Immunotherapy, using anti-lipopolysaccharide IgG, inactivates plasma endotoxins, destroys gram-negative bacteria and opsonises them and may become a major form of therapy. An outline of endotoxin and anti-lipopolysaccharide and its importance to the anaesthetist and intensive care specialist is presented.

scholarly journals Attempt to Develop Rat Disseminated Intravascular Coagulation Model Using Yamakagashi (Rhabdophis tigrinus) Venom Injection

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 160
Author(s):  
Akihiko Yamamoto ◽  
Takashi Ito ◽  
Toru Hifumi
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Clinical Condition ◽  
Underlying Disease ◽  
Fibrinogen Concentration ◽  
Blood Coagulation Factors ◽  
Fixed Amount ◽  
Intravascular Coagulation ◽  
Measurement Limit ◽  
Human Pathology ◽  
Rhabdophis Tigrinus

Disseminated intravascular coagulation, a severe clinical condition caused by an underlying disease, involves a markedly continuous and widespread activation of coagulation in the circulating blood and the formation of numerous microvascular thrombi. A snakebite, including that of the Yamakagashi (Rhabdophis tigrinus), demonstrates this clinical condition. Thus, an animal model using Yamakagashi venom was constructed. Yamakagashi venom was administered to rats, and its lethality and the changes in blood coagulation factors were detected after venom injection. When 300 μg venom was intramuscularly administered to 12-week-old rats, (1) they exhibited hematuria with plasma hemolysis and died within 48 h; (2) Thrombocytopenia in the blood was observed in the rats; (3) irreversible prolongation of prothrombin time in the plasma to the measurement limit occurred; (4) fibrinogen concentration in the plasma irreversibly decreased below the measurement limit; and (5) A transient increase in the plasma concentration of D-dimer was observed. In this model, a fixed amount of Rhabdophis tigrinus venom injection resulted in the clinical symptom similar to the human pathology with snakebite. The use of the rat model is very effective in validating the therapeutic effect of human disseminated intravascular coagulation condition due to snakebite.

Select Gram-negative Aerobic Bacteria

2012 ◽  
pp. 90-101
Author(s):  
David R. McNamara ◽  
Franklin R. Cockerill
Keyword(s):  
Cell Wall ◽  
Sepsis Syndrome ◽  
Vital Role ◽  
Klebsiella Pneumonia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Neisseria Meningitides ◽  
A Cell ◽  
Normal Human ◽  
Specific Species

Gram-negative bacteria may be rod-shaped (bacilli), spherical (cocci), oval, helical, or filamentous. Cytoplasmic membrane is surrounded by a cell wall consisting of a peptidoglycan layer and an outer cell membrane. Gram-negative bacteria are widely distributed in the natural environment. They are commensals with many animals and play a vital role in normal human physiology as intestinal commensals. Gram-negative bacteria are the cause of various human illnesses. The gram-negative bacterial cell wall contains various lipopolysaccharide endotoxins. Endotoxins trigger intense inflammation and the sepsis syndrome during infection. Specific species of gram-negative bacteria such as Neisseria meningitides, Moraxella catarrhalis, Acinetobacter, Vibrio, Klebsiella pneumonia, Salmonella, Pseudomonas aeruginosa, and Haemophilus influenza are reviewed.

Functional analysis of the lysis genes of Staphylococcus aureus phage P68 in Escherichia coli

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2331-2342 ◽  
Author(s):  
Marian Takáč ◽  
Angela Witte ◽  
Udo Bläsi
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Functional Analysis ◽  
Transmembrane Domains ◽  
Class I ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Reading Frame ◽  
Double Stranded Dna ◽  
A Cell

Double-stranded DNA phages of both Gram-positive and Gram-negative bacteria typically use a holin–endolysin system to achieve lysis of their host. In this study, the lysis genes of Staphylococcus aureus phage P68 were characterized. P68 gene lys16 was shown to encode a cell-wall-degrading enzyme, which causes cell lysis when externally added to clinical isolates of S. aureus. Another gene, hol15, was identified embedded in the −1 reading frame at the 3′ end of lys16. The deduced Hol15 protein has three putative transmembrane domains, and thus resembles class I holins. An additional candidate holin gene, hol12, was found downstream of the endolysin gene lys16 based on two predicted transmembrane domains of the encoded protein, which is a typical trait of class II holins. The synthesis of either Hol12 or Hol15 resulted in growth retardation of Escherichia coli, and both hol15 and hol12 were able to complement a phage λ Sam mutation. The hol15 gene has a dual start motif beginning with the codons Met1-Lys2-Met3…. Evidence is presented that the hol15 gene encodes a lysis inhibitor (anti-holin) and a lysis effector (actual holin). As depolarization of the membrane converted the anti-holin to a functional holin, these studies suggested that hol15 functions as a typical dual start motif class I holin. The unusual arrangement of the P68 lysis genes is discussed.

scholarly journals Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1496-1502 ◽  
Author(s):  
PM Sandset ◽  
BJ Warn-Cramer ◽  
SL Maki ◽  
SI Rapaport
Keyword(s):  
Factor Viia ◽  
Factor V ◽  
Activity Levels ◽  
Cell Surfaces ◽  
Extrinsic Pathway ◽  
Intravascular Coagulation ◽  
Disease States ◽  
Shwartzman Reaction ◽  
Thrombotic Complications

Abstract We have reported earlier that immunodepletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation (DIC) induced by infusing a low concentration of tissue factor (TF). We now describe the effect of immunodepletion of EPI in rabbits administered endotoxin. Cortisone-treated rabbits were administered anti-rabbit EPI immunoglobulin (IgG) or Fab fragments or were administered control nonimmune material before an injection of endotoxin. In four of seven rabbits administered anti-EPI, plasma EPI activity levels were reduced by 70% to 80% of initial levels for 6 to 8 hours. In these rabbits the endotoxin induced extensive DIC, as evidenced by substantial decreases in fibrinogen, factor V, factor VIII, and platelets, and gross hemorrhagic necrosis of the kidneys due to massive deposition of fibrin in the glomerular microcirculation (the generalized Shwartzman reaction). In three rabbits administered anti- EPI, plasma EPI levels were only transiently reduced. In these rabbits and in four rabbits administered nonimmune IgG or Fab, endotoxin induced minimal to moderate intravascular clotting and deposits of fibrin were not found in the glomerular capillaries. Because it is believed that TF expressed on monocytes triggers endotoxin-induced coagulation, these data are taken as evidence that EPI functions as a natural anticoagulant that can regulate factor VIIa/TF activity expressed on cell surfaces in vivo. They support a hypothesis that EPI prevents thrombotic complications that might otherwise result from exposure of blood to cytokine-induced generation of small amounts of TF on cell surfaces in many inflammatory and infectious disease states.

scholarly journals Endotoxin protein: a B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes.

1976 ◽  
Vol 144 (3) ◽  
pp. 821-827 ◽  
Author(s):  
B M Sultzer ◽  
G W Goodman
Keyword(s):  
B Cell ◽  
Lipid A ◽  
Protein A ◽  
Cell Wall Protein ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Lipopolysaccharide Endotoxin ◽  
Polyclonal Activator ◽  
A Cell ◽  
Cell Mitogen

A cell wall protein that is ordinarily complexed to the lipopolysaccharide endotoxin in gram-negative bacteria has been separated by the use of aqueous phenol. The protein is active as a B-cell mitogen and polyclonal activator of murine lymphocytes including the C3H/HeJ strain which is a nonresponder to lipoplysaccharide or lipid A.

Sequential Use of Recombinant Factor VIIa and FEIBA in a Pediatric Patient with Disseminated Intravascular Coagulation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4066-4066
Author(s):  
Paulette Bryant ◽  
Theresa Sunderland ◽  
Mark Mogul
Keyword(s):  
Pediatric Patient ◽  
Disseminated Intravascular Coagulation ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Blast Crisis ◽  
Single Agent ◽  
Philadelphia Chromosome ◽  
Coagulation Factor ◽  
Leg Pain ◽  
Intravascular Coagulation

Abstract The persistence of abnormal coagulation test results and bleeding after standard treatment in the setting of disseminated intravascular coagulation (DIC) can pose a significant challenge. Recombinant Factor VIIa (Novo Nordisk) has been used in the pediatric population for treatment of hemophilia patients with inhibitors and in various other instances as a single agent to manage coagulopathy. (1) The use of NovoSeven and FEIBA (Baxter Hyland Immune) has been reported in use of adult patients with factor deficiencies and coagulation factor inhibitors. (2) The synergistic use of NovoSeven and FEIBA to improve clinical bleeding caused by DIC in a pediatric patient is being described. A 15 year old African American male presented with a 2 month history of leg pain and a WBC of 400K. He was diagnosed with Philadelphia chromosome positive CML and treated with Allopurinol and Imatinib. After 7 months on Imatinib, he presented in septic shock. His WBC increased to 50.8K with 44% myeloblasts. Flow cytometry confirmed myeloid blast crisis. The patient was admitted to the PICU on broad spectrum antibiotics. Within 12 hours of admission, he required ventilatory assistance. Central lines were placed in the right subclavian vein, right femoral vein and left radial artery. He began bleeding from his nostrils, endotracheal tube and all of his central line sites. Mitoxantrone and Cytarabine were started. Patient was noted to have DIC with PT> 20 sec, APTT> 40 sec, platelets of 23K and D-Dimers of 11.86 (normal <0.42 mcg/ml). His Fibrinogen level was maintained above 300mg/dl during the first 8 days of admission. By hospital day 2, the patient received numerous units of FFP, platelets and PRBC, but he continued to bleed. NovoSeven was started due to volume concerns and increased bleeding. He had improvement in his coagulation tests but no improvement in his bleeding. On hospital day 3, NovoSeven was given intravenously alternating with FEIBA. The patient received NovoSeven 100 micrograms/kg IV q 12 hours. About 6 hours from the NovoSeven dose, FEIBA was given on a q 12 hour schedule at 50 units/kg IV. Significant improvement was seen with the coagulation profile immediately and the bleeding improved in 6 hours. The patient was discharged from the PICU 15 days from his admission with no clinical adverse events associated with the administration of the NovoSeven and FEIBA. He has subsequently tolerated a haploidentical transplant from his sister and he remains in continuous remission. Nigel Key and colleagues have described improved clinical clotting response with prothrombin complex concentrate (PCC) and NovoSeven. They hypothesized that the coagulation proteins in PCC have a longer half life impacting on the effectiveness of NovoSeven. (2) The use of FEIBA and NovoSeven is risky without a widely available clinical assay to assess responsiveness to NovoSeven. This anecdotal report suggests that FEIBA and NovoSeven can be given sequentially without adverse thrombotic events. Further study in monitoring NovoSeven and using sequential agents may be helpful in patients who prove unresponsive to NovoSeven alone.

scholarly journals New Diarylheptanoid from Garuga pinnata Roxb

2013 ◽  
Vol 61 (2) ◽  
pp. 131-134 ◽  
Author(s):  
Mst Taslima Khatun ◽  
M. Mahboob Ali Siddiqi ◽  
Al-Mansur MA ◽  
MH Sohrab ◽  
AFM Mustafizur Rahman ◽  
...  
Keyword(s):  
Brine Shrimp ◽  
Microbial Growth ◽  
Stem Bark ◽  
Diffusion Method ◽  
Gram Negative Bacteria ◽  
Disc Diffusion ◽  
Disc Diffusion Method ◽  
Gram Negative ◽  
Wide Range ◽  
Bacteria And Fungi

9´-Desmethylgaruganin I has been isolated from the dichloromethane extract of the stem bark of Garuga pinnata Roxb. The crude extract was screened for antimicrobial activity against a wide range of gram-positive and gram-negative bacteria and fungi by disc diffusion method and cytotoxicity by brine shrimp lethality bioassay. The dichloromethane extract showed moderate inhibitory activity to microbial growth and weak cytotoxicity having LC90 25.703?g-mL–1 DOI: http://dx.doi.org/10.3329/dujs.v61i2.17058 Dhaka Univ. J. Sci. 61(2): 131-134, 2013 (July)

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