Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrinogen (Fg), plasminogen (Plg), alpha 2-antiplasmin (alpha 2-AP), plasminogen activator (PA), tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (DD) and fibrin(ogen) degradation products (FDP) were studied in 60 subjects: 40 patients with endemic hepatosplenomegaly (20 during acute haematemesis from ruptured oesophageal varices, 20 with endemic hepatosplenomegaly assigned to the same grade of oesophageal varices but with no history of haematemesis) and 20 normal controls. All parameters were markedly altered in the disease groups. Reduced levels of Fg, Plg, alpha 2-AP and PAI were associated with increasing levels of PA, t-PA, DD and FDP. Alterations were most marked in the group complicated by acute bleeding. It was concluded that these patients have an enhanced fibrinolytic state. This was probably aggravated in the haematemesis group by an acute haemostatic imbalance that superimposed the low grade chronic DIC reported in cases of hepatosplenic schistosomiasis.
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PMID:Fibrinolytic parameters during acute haematemesis in endemic hepatosplenomegaly. 814 81

A normally functioning hemostasis system is closely related to liver function. The liver parenchymal cells produce most of the factors and inhibitors of the clotting and fibrinolytic systems, and the RES of the liver greatly aids in the clearance of activation products. Hemostasis defects thus depend on the extent of liver damage. A wide spectrum of defects is found in patients with liver cirrhosis. Owing to impaired protein synthesis, most factors and inhibitors of the clotting and the fibrinolytic systems are markedly reduced. Additionally, abnormal vitamin K-dependent factor and fibrinogen molecules have been encountered. Most patients have hyperfibrinolysis that could be DIC in nature. Thrombocytopenia and thrombocytopathy are also found. Acute or chronic hepatocellular disease may display decreased vitamin K-dependent factor levels, especially factor VII and protein C, with other factors still being normal. If patients go into hepatic failure, the abnormalities resemble those found in liver cirrhosis. Vitamin K deficiency is associated with the production of poorly functioning vitamin K-dependent factors. All other hemostasis parameters are normal. Disturbances associated with liver surgeries again depend on the underlying liver problem. Peritoneovenous shunts (LeVeen) may lead to DIC; bleeding from partially resected liver surfaces is usually a mechanical problem. Severe bleeding is encountered with orthotopic liver transplantation. It is greatly influenced by the activation of the fibrinolytic system. This occurs during the anhepatic phase and during the reperfusion phase. The hyperfibrinolysis is mediated by an intense release of t-PA. Antifibrinolytic drugs, if used cautiously, have markedly reduced bleeding and thus reduced need for blood and blood product substitution.
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PMID:Coagulation defects in liver disease. 817 Feb 58

Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) are the most important factors involved in the regulation of blood fibrinolysis. t-PA converts zymogen plasminogen to plasmin on the surface of endothelial cells to maintain blood fluidity and on the surface of the thrombus to efficiently lyse the thrombus. In circulating plasma, PAI-1 inactivates t-PA by forming an equimolar complex with t-PA to suppress the hyperfibrinolysis of the blood. Both proteins are synthesized by the vascular endothelial cells and secreted from the cells in resting state and in response to several stimuli such as thrombin, endotoxin, cytokines and growth factors. In various diseases such as DIC, thromboembolism and bacterial infection, the plasma concentrations of those two factors vary as a consequence of several stimuli, representing the altered fibrinolytic balance caused by the disease. Measurements of these factors and evaluation of the fibrinolytic balance will be important for determination of the most appropriate method of treatment. Moreover, the high plasma concentration of PAI-1 will be a prognostic marker of the disease and may be a risk factor of thrombotic events. In clinical treatment, t-PA is now widely used as a valuable fibrinolytic agent especially in myocardial infarction.
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PMID:[Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)]. 817 42

Plasma interleukin-6 (IL-6) was higher in patients with disseminated intravascular coagulation (DIC) than in those without DIC. Levels of IL-1 beta and TNF alpha were also significantly higher in patients with DIC. Plasma IL-6 was highest in patients with underlying sepsis and was also high in those with advanced solid cancer. Levels were high in some patients with acute promyelocytic leukaemia and were significantly higher in patients with organ failure than in those without this complication. Plasma IL-6 was higher in DIC patients showing a poor response to therapy than in those with a good response. Incubation with IL-6 caused significant increases in tissue factor activity in mononuclear cells and release of plasminogen activator-1 antigen from human umbilical vein endothelial cells. As increases in IL-6 might give rise to hypercoagulable and hypofibrinolytic states, this may be a cause of DIC and be related to prognosis and organ failure.
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PMID:Increased plasma level of interleukin-6 in disseminated intravascular coagulation. 821 55

In patients with disseminated intravascular coagulation (DIC), hyperfibrinolysis was observed in patients with leukaemia, but hypofibrinolysis was seen in those with sepsis. Although the plasma tissue plasminogen activator (t-PA) level was higher in patients with DIC than in those without DIC, there was no significant difference in t-PA level between the patients with leukaemia and sepsis. Hyperfibrinolysis might not be caused by t-PA derived from leukaemic cells, although the PA antigen level in leukaemic cell homogenates was significantly higher in patients with DIC than in those without DIC. The activation of t-PA by leukaemic cell homogenates in the absence of bromocyan fibrinogen fragments suggested that leukaemic cell homogenates had t-PA stimulator activity. The t-PA stimulator activity was high in both acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL), especially in DIC, but this activity was not detected in chronic myelocytic leukaemia (CML) or normal cells. Since fibrinogen and soluble fibrin monomer complex levels in leukaemic cells were also high in patients with DIC, fibrinogen degradation products might be the major t-PA stimulator in leukaemic cells. This might be one of the causes of hyperfibrinolysis in leukaemia.
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PMID:Stimulation of tissue type plasminogen activator by leukaemic cell homogenates. 821 56

We found that patients with thrombotic thrombocytopenic purpura (TTP) have significantly elevated plasma thrombin antithrombin III complex (TAT) and FDP-D-dimer levels, while the plasmin-alpha 2 plasmin inhibitor complex (PIC) level was only slightly increased. The tissue-type plasminogen activator (t-PA) level was increased, but it was well correlated with the plasminogen activator inhibitor-I (PAI-I) level. These findings suggest that hypercoagulable and hypofibrinolytic states coexist in these patients, in contrast to patients with disseminated intravascular coagulation, who exhibit coexisting hypercoagulable and hyperfibrinolytic states. Levels of vascular endothelial cell markers, such as PAI-I, thrombomodulin (TM), and t-PA, were increased at the onset of TTP, but the level of von Willebrand factor (vWF) antigen was not increased. The outcome in TTP patients was correlated with plasma t-PA and TM levels but not with TAT or PIC. These results suggest that vascular endothelial cell markers, such as TM and t-PA, are released from injured or stimulated endothelial cells, reflecting the degree of vascular endothelial damage, and that the main factor in the pathogenesis of TTP is vascular endothelial cell injury.
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PMID:Increased levels of vascular endothelial cell markers in thrombotic thrombocytopenic purpura. 826 13

We examined vascular endothelial cell markers, thrombomodulin (TM), plasminogen activator inhibitor-I (PAI-I), tissue plasminogen activator (t-PA), and von Willebrand factor, in 80 patients with disseminated intravascular coagulation (DIC). The levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC) and FDP-D-dimer were significantly increased both before and after the onset of DIC, but were not correlated with organ failure or prognosis. However, the PIC/TAT ratio was lower in patients with poor prognosis than in those with good prognosis, and it was also lower in those with organ failure than in those without. Plasma TM, PAI-I, and t-PA levels were increased in DIC patients with organ failure or poor outcome, but were not significantly increased before the onset of DIC. We consider that the prognosis of patients with DIC might be related to organ failure or endothelial cell damage and that plasma levels of TM, PAI-I, and t-PA might be useful in the detection of these disorders and in assessing prognosis. A hypofibrinolytic state might enhance organ failure in patients with DIC.
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PMID:Increased vascular endothelial cell markers in patients with disseminated intravascular coagulation. 826 24

Disseminated intravascular coagulation in association with arterial aneurysm has been reported in several cases. Reports have suggested a continuous deposition of fibrin and/or platelets at the site of the aneurysm followed by fibrinolysis as responsible for this disorder. To further investigate this theory we studied the in vivo binding of an indium-111-labelled monoclonal antibody against human tissue plasminogen activator (t-PA), a proteolytic enzyme involved in the fibrinolysis. Six patients admitted to the hospital for elective resection of an abdominal aortic aneurysm with a mural thrombus were examined. One day before the operation the antibody was injected intravenously. Scintigrams acquired just prior to operation and tissue samples obtained at the operation revealed an increased t-PA accumulation in the wall of the aneurysm. The study demonstrates in vivo, focally increased fibrinolytic activity in the aneurysm, explaining the coagulopathy observed in these patients.
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PMID:In vivo demonstration of focal fibrinolytic activity in abdominal aortic aneurysms. 827 70

New assays for thrombin-antithrombin III complex, plasmin-alpha 2-plasmin inhibitor complex, FDP-D-dimer, t-PA/PAI-1 complex and prothrombin fragment F1+2 are reviewed as molecular markers for disseminated intravascular coagulation (DIC). These are sensitive to early stage indication of DIC. Fluctuation of their levels was also relative to the state of DIC. It is therefore believed that they will play an important role in the diagnosis of DIC, as solid members of its parameter. On the other hand, t-PA/PAI-1 complex is suggested to be the complication marker of DIC, such as multiple organ failure (MOF), as its level was thought to reflect endothelial cell stimulation during DIC.
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PMID:[New useful parameters or makers in diagnosis and condition. Analysis of disseminated intravascular coagulation--mainly molecular markers]. 843 26

Ancrod is a purified coagulant venom which renders blood incoagulable by cleaving fibrinopeptide A (FPA) from fibrinogen, but the mechanism involved in the clearance of fibrin from the circulation is unknown. To investigate the fibrinolytic response to ancrod, and to increase understanding of clearance mechanisms, six patients with peripheral vascular disease causing claudication were infused with ancrod at 2 u/kg over 6 h followed by 2 u/kg at 12 h intervals for 38 h. Venous blood samples were taken at time 0, 3, 6, 25 and 49 h for assay of fibrinogen (Fbg), fibrinopeptide A (FPA), total fibrin(ogen) degradation products (TDP), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (tPA), urinary type plasminogen activator (u-PA), plasminogen, alpha 2 antiplasmin (alpha 2 AP) and plasminogen activator inhibitor-1 (PAI-1). Fibrinogen (median and range) was 2.3 (1.4-3.90) g/l at time 0 and thereafter was undetectable. FPA rose from 2.5 (1.8-3.6) to 600 and 188 pmol/l at 3 h and 6 h and remained elevated. TDP, FbDP and FgDP increased greatly following ancrod while there was no evidence of XL-FDP. The surprising increase in FgDP during defibrination suggests either that fibrinogen is digested following its incorporation into circulating fibrin protofibrils or that some of the fibrin subunits in the photofibril retain one of the two fibrinopeptide A's. tPA and uPA remained unchanged. Plasminogen fell from 125 (100-155)% to 79 (40-118)% at 49 h and alpha 2 AP fell from 91 (75-107)% to 24 (10-35)% at 49 h. The level of PAI-1 was depressed during defibrination, with the exception of the 6 h data. The results demonstrate that ancrod removes FPA from fibrinogen to produce non-cross-linked (soluble) fibrin. This is cleared from the circulation without evidence of an increase in the circulating activities of the plasminogen activators, tPA or UK, but with evidence of plasminogen activation and consumption.
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PMID:The fibrinolytic response to ancrod therapy: characterization of fibrinogen and fibrin degradation products. 845 76


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