scholarly journals Histopathologic and Electron Microscopic Studies on the Acute Toxicity of Ochratoxin A in Rats

1987 ◽  
Vol 24 (5) ◽  
pp. 427-435 ◽  
Author(s):  
M. A. Albassam ◽  
S. I. Yong ◽  
R. Bhatnagar ◽  
A. K. Sharma ◽  
M. G. Prior
Keyword(s):  
Ochratoxin A ◽  
Disseminated Intravascular Coagulation ◽  
Villous Atrophy ◽  
Endothelial Damage ◽  
Male Rats ◽  
Lymphoid Tissues ◽  
Necrotic Enteritis ◽  
Electron Microscopic ◽  
Intravascular Coagulation ◽  
Glomerular Capillaries

Ochratoxin A was given by gavage to male rats. Moribund and dead animals were necropsied, and the surviving rats, including the controls, were killed 48 hours after dosing. Many of the principal rats were moribund, or began dying, within 12 to 24 hours after dosing. Lesions suggestive of disseminated intravascular coagulation were seen by light microscopy as early as 12 hours after dosing; fibrin deposits were in the spleen, brain choroid plexus, glomerular capillaries, liver, and heart. Renal tubular nephrosis, hepatic and lymphoid necrosis, and necrotic enteritis with villous atrophy were also seen. Electron microscopy demonstrated fibrin strands mixed with degranulated platelets, necrotic leukocytes, and swollen endothelial cells in glomerular capillaries. Myocardial changes included focal supercontracted sarcomeres adjacent to intercalated disks. Swollen sarcolemma, lysed myofibrils and fragmented Z-bands with interstitial edema, vascular thrombosis, and endothelial damage were also seen. The acute pathologic changes induced by ochratoxin A in the intestine, liver, and lymphoid tissues were more obvious than the tubular nephrosis, and the development of a disseminated intravascular coagulation-like syndrome with myocardial changes was a complicating factor.

scholarly journals Endothelial Dysfunction Is Associated with Mortality and Severity of Coagulopathy in Patients with Sepsis and Disseminated Intravascular Coagulation

2019 ◽  
Vol 25 ◽  
pp. 107602961985216 ◽  
Author(s):  
Amanda Walborn ◽  
Matthew Rondina ◽  
Michael Mosier ◽  
Jawed Fareed ◽  
Debra Hoppensteadt
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
High Mobility ◽  
Severity Of Illness ◽  
Endothelial Activation ◽  
Endothelial Damage ◽  
Intravascular Coagulation ◽  
Angiopoietin 2 ◽  
Von Willebrand ◽  
Relationship Of

The role of the endothelium in sepsis-associated disseminated intravascular coagulation (DIC) is multifaceted and may contribute substantially to disease severity and outcome. The purpose of this study was to quantify measures of endothelial function, including markers of activation (endocan, Angiopoietin-2 [Ang-2], and von Willebrand Factor), endogenous anticoagulants (tissue factor pathway inhibitor and protein C), and damage-associated factors (High Mobility Group Box 1 [HMGB-1]) in the plasma of patients with sepsis and DIC, and to determine the relationship of these factors with severity of illness and outcome. Plasma samples were collected from 103 adult patients with sepsis within 48 hours of intensive care unit admission. Biomarker levels were measured using commercially available, standardized methods. Disseminated intravascular coagulation was diagnosed according to the International Society of Thrombosis and Hemostasis scoring algorithm. Twenty-eight-day mortality was used as the primary end point. In this study, endothelial damage and dysfunction were associated with the severity of coagulopathy and mortality in DIC patients. Loss of the endogenous anticoagulant protein C and elevation in the vascular regulator Ang-2 were associated with the development of overt DIC. In addition to Ang-2 and protein C, endocan, a biomarker of endothelial activation, and HMGB-1, a mediator of endothelial damage and activation, were significantly associated with mortality. This underscores the contribution of the endothelium to the pathogenesis of sepsis-associated DIC.

scholarly journals Thrombotic Thrombocytopenic Purpura: Report of a Case With Disseminated Intravascular Platelet Aggregation

Blood ◽  
1973 ◽  
Vol 42 (5) ◽  
pp. 805-814 ◽  
Author(s):  
P. B. Neame ◽  
J. Lechago ◽  
E. T. Ling ◽  
A. Koval
Keyword(s):  
Platelet Aggregation ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Disseminated Intravascular Coagulation ◽  
Endothelial Lining ◽  
Electron Microscopic ◽  
Thrombocytopenic Purpura ◽  
Intravascular Coagulation ◽  
Coagulation Study ◽  
Platelet Aggregates ◽  
Vascular Occlusions

Abstract The nature and etiology of the vascular occlusions encountered in thrombotic thrombocytopenic purpura (TTP) have been subject to controversy for a number of years. Disseminated platelet thrombosis has been suggested in the earlier literature, although later views have favored fibrin thrombi resulting from vascular damage or disseminated intravascular coagulation (DIC). The serial coagulation study and the lightand electron-microscopic findings in a case of TTP are described here. The multiple vascular occlusions were due to the presence of densely packed platelet aggregates in which a variable quantity of fibrin was present. Less commonly, loose platelet aggregates were noted. Fibrin under the endothelial lining was occasionally observed in relationship to the vascular occlusion and was thought to be secondary to the release of various substances from aggregating platelets. The serial coagulation study and the histologic examination of tissues showed no evidence of disseminated intravascular coagulation. This case shows that the occlusions observed in TTP can be due to disseminated intravascular platelet aggregation in the absence of DIC. Although TIP might be of variable etiology, it is felt that cases showing disseminated intravascular platelet aggregation should be distinguished from DIC in order to plan therapy on a rational basis.

Biochip Array Analysis of Various Mediators of Inflammation in Disseminated Intravascular Coagulation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2302-2302 ◽  
Author(s):  
Saud Rahman ◽  
Debra Hoppensteadt ◽  
Josephine Cunanan ◽  
Rachael Davis ◽  
Nasir Sadeghi ◽  
...  
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Conflicts Of Interest ◽  
Vascular Dysfunction ◽  
Tumor Necrosis Factor Receptor ◽  
Neuron Specific Enolase ◽  
Endothelial Damage ◽  
Intravascular Coagulation ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Mediators Of Inflammation ◽  
Circulating Levels

Abstract Abstract 2302 Disseminated intravascular coagulation is a polypathologic syndrome which involves blood, endothelial and target organ dysfunction resulting in the generation of various mediators of vascular dysfunction, hemostatic aberrations and hemodynamic disturbances. In addition, various disorders of target organs such as kidney, liver, heart and brain are observed. Uncontrolled protease generation results in the formation of various mediators of inflammation such as neuron specific enolase (NSE), neutrophil gelatinase associated lipocalin (NGal) and soluble tumor necrosis factor receptor 1 (TNF R1). Endothelial damage results in the generation of thrombomodulin (TM) and endogenous coagulation/fibrinolysis results in D- Dimer formation. In order to study the circulating levels of these mediators, a Biochip array method (Randox, Oceanside, CA) was utilized with samples obtained from clinically diagnosed DIC (n=100) and normal individuals (n=10). The results are summarized in the following table. Circulating levels of these mediators were markedly increased in DIC patients in comparison to normals. The most striking increase was noted in NGal (4–6 fold) and TNF R1 (10 fold). Other mediators were also increased in the DIC group, however the data was broadly scattered. These results indicate that beside the aberration in the hemostatic system NGal and TNF R1 along with other inflammatory mediators may play a major role in the pathophysiology of DIC.MarkerNormal ControlsDIC BaselineCRP (ug/ml)3.47 + 0.913.11 + 0.2*NSE (ng/ml)6.11 + 8.610.78 + 1.6*NGAL(ng/ml)306.45 + 25.51376.56 + 48.5*TNFR1 (ng/ml)0.35 + 0.013.89 + 0.3*DD (ng/ml)232.8 + 74.41318.94 + 80.5*TM (ng/ml)3.4 + 0.33.16 + 0.2 P=<0.05 Disclosures: No relevant conflicts of interest to declare.

The Elimination of Labelled Fibrinogen in Galactosamine-Induced Experimental Hepatitis in Rabbits

1975 ◽  
Author(s):  
I. Mahn ◽  
C. Reuter ◽  
H. Merkel ◽  
G. Müller-Berghaus
Keyword(s):  
Liver Disease ◽  
Intravenous Injection ◽  
Disseminated Intravascular Coagulation ◽  
Isotonic Saline ◽  
Coagulation Factors ◽  
Virus Hepatitis ◽  
Intravascular Coagulation ◽  
Coagulation Defect ◽  
Deutsche Forschungsgemeinschaft ◽  
Glomerular Capillaries

The intravenous injection of D-galactosamine-HCl into animals induces a liver disease resembling virus hepatitis in man in its histological and clinico-phatological features. In a previous study disseminated intravascular coagulation was demonstrated by tracing fibrin-rich microdots in the renal glomerular capillaries, especially if the fibrinolytic system was inhibited by EACA (Thromb. Res. 1, 473, 1972). In order to differentiate between disturbance of synthesis and disseminated intravascular coagulation, investigations with 125I-fibrinogen were performed in rabbits treated with D-galactosamine (1 g/kg) and EACA (0.5 g/kg xhr). In rabbits infused with galactosamine and EACA the elimination of 125I-fibrinogen was increased in comparison to the control animals treated with EACA or isotonic saline only. If heparin (750 u/kg × hr) was infused additionally to galactosamine and EACA, the accelerated decay of labelled fibrinogen was prevented. The occurrence of 125I-activity in organs was pronounced in animals exhibiting microdot formation. These experiments indicate that due to a diminished synthesis of coagulation factors in this model of hepatitis disseminated intravascular coagulation may contribute to the coagulation defect.(Supported by the Deutsche Forschungsgemeinschaft, Bad Godesberg, Germany.)

scholarly journals Systemic Inflammatory Response Syndrome in Nonhuman Primates Culminating in Multiple Organ Failure, Acute Lung Injury, and Disseminated Intravascular Coagulation

2009 ◽  
Vol 37 (6) ◽  
pp. 799-804 ◽  
Author(s):  
Renee R. Hukkanen ◽  
H. Denny Liggitt ◽  
Robert D. Murnane ◽  
Charles W. Frevert
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Disseminated Intravascular Coagulation ◽  
Experimental Manipulation ◽  
Endothelial Damage ◽  
Multiple Organ ◽  
Systemic Inflammatory Response ◽  
Major Surgery ◽  
Intravascular Coagulation ◽  
Toxicological Studies

The systemic inflammatory response syndrome (SIRS) is a clinicopathological manifestation of overexuberant acute-phase inflammation caused by infectious or noninfectious etiologies. The systemic release of pro-inflammatory cytokines, chemokines, and lipid and vasoactive mediators induces endothelial damage and microvascular thrombosis, potentially culminating in disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MOD) or failure (MOF). We present five cases in the pig-tailed macaque and olive baboon where SIRS resulted in MOF, ARDS, DIC, and the Waterhouse-Friderichsen syndrome; each with gross and histological elements manifested as edema, deposition of fibrin, hemorrhage, and thrombosis. In the described cases, SIRS was the end-common pathway for multiple risk factors that parallel those documented in humans: major surgery, obstetric complications, and infection. The diagnosis of SIRS should be considered when evaluating nonhuman primate (NHP) cases of MOF manifesting with histological evidence of vascular leakage. Experimental manipulation of NHP models may be complicated by SIRS and accompanying rapid clinical decompensation. Such adverse events may compromise toxicological studies and should be avoided when possible.

scholarly journals An Electron Microscopic Study of Thrombin-Induced Disseminated Intravascular Coagulation

Blood ◽  
1967 ◽  
Vol 29 (2) ◽  
pp. 169-181 ◽  
Author(s):  
WILLIAM MARGARETTEN ◽  
ILONA CSAVOSSY ◽  
DONALD G. McKAY
Keyword(s):  
Light Microscopy ◽  
Rat Kidney ◽  
Reticuloendothelial System ◽  
Electron Microscopic ◽  
Intravascular Coagulation ◽  
Major Mechanism ◽  
Shwartzman Reaction ◽  
Kidney Liver ◽  
Fibrin Thrombi ◽  
Glomerular Capillaries

Abstract Fibrin thrombi due to slow intravascular coagulation appear simultaneously in rat kidney, liver, lung, and spleen, although the kidney is the only organ to show fibrin by light microscopy. The strands of fibrin are frequently associated with aggregation and viscous metamorphosis of platelets, particularly in the lungs. Some fibrin is eliminated by the reticuloendothelial system and through damaged glomeruli, but the major mechanism of removal is intravascular dissolution. Ischemic changes secondary to thrombosis are more prominent in glomerular capillaries than in other tissues. The morphologic observations are discussed in relation to "preparation" for the generalized Shwartzman reaction.

Fibrin Deposition and Removal in Disseminated Intravascular Coagulation Induced by Endotoxin and Saline Loading: Radioautographic Findings in Rats

1978 ◽  
Vol 40 (02) ◽  
pp. 499-511 ◽  
Author(s):  
H Heyes ◽  
W Mohr ◽  
W Theiss
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Degradation Products ◽  
Radioactive Material ◽  
Fibrin Deposition ◽  
Intravascular Coagulation ◽  
Saline Loading ◽  
Shwartzman Reaction ◽  
Kidney Liver ◽  
Kinetics Of ◽  
Glomerular Capillaries

SummaryIn rats a single injection of endotoxin followed by an infusion of normal saline induced the generalized Shwartzman reaction. The presence of disseminated intravascular coagulation (DIC) was demonstrated by measuring plasma fibrinogen, platelet counts, schistocytes, plasma haemoglobin, fibrin(ogen) degradation products, and fibrin thrombi in the glomerular capillaries. 125I-fibrinogen was given after triggering DIC in order to examine the fibrinogen turnover in plasma and the kinetics of fibrin deposition and removal in kidney, liver, and spleen. 125I-fibrinogen turnover was found to be highly accelerated. Early deposition and removal were observed in the kidneys, while a later peak with a more delayed fall of radioactivity was noted in liver and spleen. On histological examination fibrin could be seen only in the glomerular capillaries and only in the early phase of DIC. In radioautographs radioactive material was localized in the glomerular capillaries, the Kupffer’ cells of the liver, and in the perifollicular macrophages of the spleen. Comparing the results obtained by scintillation counting to those obtained by light microscopy it can be assumed that radioactivity in kidneys is correlated to fibrin deposition in glomerular capillaries and to an accumulation of fibrin(ogen) degradation products in liver and spleen.

Disseminated intravascular coagulation and status epilepticus

Neurology ◽  
1998 ◽  
Vol 51 (2) ◽  
pp. 629-631 ◽  
Author(s):  
A. Felcher ◽  
C. Commichau ◽  
Q. Cao ◽  
M. J. Brown ◽  
A. Torres ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Body Temperature ◽  
Disseminated Intravascular Coagulation ◽  
Laboratory Data ◽  
Endothelial Damage ◽  
Autopsy Findings ◽  
Intravascular Coagulation

Status epilepticus has been associated with disseminated intravascular coagulation (DIC), but little is known regarding the pathogenesis of this uncommon association. We describe a 41-year-old woman with status epilepticus resulting in death in whom laboratory data demonstrated profound activation of the coagulation and fibrinolytic systems; autopsy findings were consistent with DIC. The occurrence of DIC in status epilepticus may be related to widespread endothelial damage secondary to seizure-induced hyperpyrexia. Body temperature should be closely monitored in patients with prolonged seizures.

CARE OF THE CRITICALLY ILL CHILD: THE PROBLEM OF DISSEMINATED INTRAVASCULAR COAGULATION

PEDIATRICS ◽  
1970 ◽  
Vol 46 (5) ◽  
pp. 767-773
Author(s):  
William E. Hathaway
Keyword(s):  
Critically Ill ◽  
Disseminated Intravascular Coagulation ◽  
Signs And Symptoms ◽  
Coagulation Factors ◽  
Endothelial Damage ◽  
Bleeding Diathesis ◽  
Intravascular Coagulation ◽  
Laboratory Confirmation ◽  
Tissue Thromboplastin ◽  
Critically Ill Child

A critically ill child should be suspected of the complication of disseminated intravascular coagulation when evidence of the following signs and symptoms are present: (1) the potential of a triggering substance or event such as endotoxin, tissue thromboplastin (damaged tissue), endothelial damage, or proteolysis; (2) multiple system involvement producing coma, renal shutdown, respiratory disease, and shock; (3) a bleeding diathesis; and (4) a hemolytic anemia associated with fragmented and burred red cells. Laboratory confirmation should include evidence for depletion of coagulation factors consumed during clotting (i.e., platelets, fibrinogen, and factors II, V, and VIII). Treatment consists of heparinization, replacement of depleted factors if needed, and supportive care, which includes removal of the triggering event.

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