Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Influence of acute portal vein occlusion on blood coagulation and fibrinolysis have not been fully clarified. In this experimental study in mongrel dogs, 1) changes of blood coagulation and fibrinolysis in portal vein and peripheral vein, 2) histological changes in small intestine and 3) activity of plasminogen activator in small intestine were investigated periodically after acute portal vein ligation with or without heparinized hydrophilic catheter-bypass between portal and femoral vein. All five dogs died 81-130 minutes (mean 105 minutes) after portal vein ligation. On the other hand, all five bypassed dogs survived in good condition for more than four hours. Acute portal venous congestion caused hypercoagulable state in portal system and apparent DIC occurred in portal system 10 minutes after portal vein ligation. Activity of tissue plasminogen activator which was observed mostly in the endothelial cells of vessels in submucosal layers of small intestine decreased rapidly and disappeared within 20 minutes after portal vein ligation. To the contrary, with the use of the catheter-bypass procedure, no significant changes of blood coagulation and fibrinolysis were observed. These results indicate clearly that portal venous congestion is the trigger of hypercoagulable state in portal system, which progresses to irreversible DIC in 20 minutes. With the use of the catheter-bypass procedure, portal vein shut-down is performed without any abnormal coagulation and fibrinolysis in portal bed and systemic circulation.
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PMID:[The experimental study of blood coagulation and fibrinolysis in acute portal vein occlusion]. 668 31

I have experienced 35 cases of DIC in my department during last 8 years. These cases were divided into a septic and non-septic groups based on their back-ground, and compared their clinical symptoms and various laboratory findings. The results showed the septic DIC group could be characterized as follows: (1) impairment of the vital organs was more clearly manifested, while hemorrhagic symptoms were mild, (2) the laboratory tests showed almost no tendency for fibrinogen or alpha 2-PI to be decreased or PIC to be increased, (3) the blood PAF (Platelet Activating Factor) level was clearly higher and showed an inverse relationship with the platelet count. On the basis of these clinical findings, I speculated septic DIC involves suppression of secondary fibrinolysis and participation of PAF. In experiment A, I investigated the effects of endotoxin (Et) on the activity of plasminogen activator (PA) in the rabbit renal cortex. In both in vitro and in vivo systems, I could demonstrate the renal cortex PA activity was significantly suppressed by Et. Then, in experiment B, I could confirm, (1) PAF caused a drop in the blood pressure and a decrease in the platelet count that were similar to those induced by Et, and that Et caused a decrease in the platelet count that was inversely accompanied by an increase in PAF, (2) PAF antagonist showed greater efficacy than a protease inhibitor in suppressing the decrease in the blood platelet count.
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PMID:[Clinical and experimental studies of septic DIC in surgical patients, in terms of its characteristic features and pathogenesis]. 787 83

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

During activation of the fibrinolytic system plasminogen is converted to plasmin by tissue plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). t-PA is predominantly released from endothelial cells, u-PA primarily by renal parenchymal cells. The activation of plasminogen is regulated by plasminogen activator inhibitor-1 (PAI-1), plasmin is controlled by alpha 2-plasmin inhibitor. The fibrinolytic system is not only involved in the intravascular dissolution of fibrin (thrombi), it also plays a vital role in normal physiologic reproduction, wound repair, angiogenesis, and tissue remodeling. Fibrinolysis is also a vital component in the pathogenesis of neoplastic disease. It is essential in releasing cells from their primary site of origin, providing nutrition for neoplastic cell growth and promoting cell mobility and motility. In neoplastic cells the degradation of the extracellular matrix proteins is facilitated by excessive expression of u-PA, t-PA, and u-PAR. In many forms of carcinoma increased expression of u-PAR and u-PA is associated with significantly shorter survival. Greater expression of u-PA in breast cancer cells, for example, is associated with shorter survival and increased relapse rate. Progressively aggressive neoplastic cells evidence high expression of u-PA and u-PAR activities, variable expression of t-PA, and enhanced PAI-1 and PAI-2 activities. In acute nonlymphocytic leukemias, poor outcome correlates with high t-PA levels. In acute progranulocytic leukemia there is a high incidence of DIC. Neoplastic prostatic tissue also expresses high u-PA activity and the more aggressive the cell line, the greater the number of u-PAR and the higher the u-PA activity. In gynecologic malignancies, a greater expression of u-PA in combination with cathepsin D is associated with widespread disease and poor prognosis. High u-PA values were also seen in patients with brain, gastric, and hepatic malignancies. It is evident that the plasminogen-plasmin system is a vital component in the biology of neoplastic disease and that it is, in theses conditions, in no way beneficial to the host.
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PMID:The fibrinolytic system in neoplasia. 912 11

The etiology of acute pancreatitis is based on several causes, among which idiopathic nature (< 30%) is second to biliary stone disease (60-70%). It is still under debate whether alcohol as the main cause of chronic pancreatitic disease can cause acute pancreatitis. Based on Opie's "obstruction theory" of 1901 and experimental data, it is now widely accepted that the gallstone passage into or through the terminal biliopancreatic ductal system triggers acute (necrotizing) pancreatitis by causing pancreatic ductal obstruction. However, the sequential intracellular mechanisms in the pathogenesis of acute pancreatitis remain unclear. A co-localization hypothesis has been proposed to explain the premature intracellular activation of trypsinogen to trypsin: due to a yet unknown defect in the intracellular protein transport and sorting system within the acinar cell, lysosomal hydrolases (i.e. cathepsin B) and secretory proteins (i.e. trypsinogen) co-localize in a fragile postgolgi vacuole where activation can occur. In addition, alterations of exo- and endocytosis at the apical pole exist (i.e. secretion block). The pathophysiological events are characterized by local and systemic hypovolemia and (micro)circulatory failure aggravating necrosis, followed by ARDS, renal failure and several other severe complications (i.e. sepsis and DIC). The systemic overflow of proteolytic enzymes (i.e. PLA-2) and kinins plays a major role as mediating factor in severe cases, resulting in multiorgan failure.
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PMID:[Etiology, pathogenesis and pathophysiology of acute pancreatitis]. 928 10

An investigation was made for the significance of changes of coagulation and fibronolytic system in intensive infection with multiple system organ failure (MSOF). In 68 cases with various degrees of infection, hematological examinations, including estimation of PT, APTT, Fg, Fn and D-Dimer, activation of coagulation factor II, VII, X, XII (F II, F VII, F X, F XII), AT-III, PLG, alpha(2)-AP, t-PA and count of platelets were carried out. The results were as follows: In intensive infection with MSOF, PT and APTT increased significantly; activity of F II, F VII, F X and F XII decreased significantly platelet count and Fn decreased markedly; concentration of Fg and D-Dimer increased significantly; activity of PAI increased markedly; activity of t-PA and alpha(2)-AP decreased slightly. The incidence of MSOF not combined with DIC was 38.5%, but that combined with DIC was 79.7% (P < 0.01). It is suggested that DIC is the most important factor in the disorder of coagulation and fibrinolytic system. It play an important role in the pathogenesis and development of MSOF.
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PMID:[An investigation on the changes of coagulation and fibrinolytic system in intensive infection with multiple organs failure]. 959 27

We evaluated the effect of r-hirudin and/or tissue-plasminogen activator (t-PA) in a model of DIC in rabbits induced by i.v. infusion of 100 micrograms/kg/h/6 h endotoxin. Rabbits were treated with saline (endotoxin control group), r-hirudin at 0.3 mg/kg/h/6 h, t-PA at 0.3 mg/kg for 90 min and r-hirudin plus t-PA at the doses described above. The best results were achieved when r-hirudin and t-PA were infused together. This treatment reduced the consumption of platelets and protein C and attenuated the increase of PAI-1 more efficiently than r-hirudin or t-PA alone. r-Hirudin plus t-PA also resulted in the lowest formation of fibrin deposits in the kidneys. Finally, mortality at 24 h dropped from 70% in the endotoxin control group to 40%, 10% and 0% in the t-PA, r-hirudin and r-hirudin plus t-PA groups respectively. None of the t-PA-infused rabbits which had died by 24 h showed macroscopic signs of haemorrhage. r-Hirudin alone was better than t-PA alone, as was shown by fibrin deposits and mortality. We conclude that r-hirudin and t-PA given simultaneously were more efficient than either given alone in this model of DIC. Effective thrombin inhibition, which could influence other pathophysiological mechanisms apart from coagulation, together with the improvement in fibrinolysis, would explain these results.
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PMID:Effect of the administration of recombinant hirudin and/or tissue-plasminogen activator (t-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits. 1023 73

This study evaluated hemostatic data in 28 patients with newly diagnosed acute promyelocytic leukemia (APL) and 15 patients with relapsed APL. Activated partial thromboplastin time and prothrombin time were prolonged at initial onset of APL. Plasma level of fibrinogen was significantly decreased in patients with initial disease of APL, but it was not decreased significantly during the relapse of APL. Plasma fibrin and fibrinogen degradation products levels were significantly increased and platelet counts significantly decreased in both groups. Plasma levels of antiplasmin significantly decreased at initial onset but not during relapse. Plasma levels of antithrombin were within normal range in patients with initial disease but significantly decreased in those with relapse. Plasma levels of D-dimer, soluble fibrin monomer (sFM), plasmin-plasmin inhibitor complex (PPIC), and thrombin antithrombin complex (TAT) levels were significantly high in both groups. Plasma levels of PPIC, sFM, and D-dimer were significantly higher at initial onset of APL than during relapse. However, there was no significant difference in DIC score between patients with initial onset and those with relapse; plasma levels of tissue factor (TF) significantly increased in both groups, but they were significantly higher at initial onset of APL than during relapse. TF and tissue type plasminogen activator (t-PA) antigen levels in leukemic cell lysate were significantly increased in both groups, and they were significantly lower during relapse than at initial onset. Hemostatic abnormalities occurring in patients with relapsed APL might be the result of the decrease of TF and t-PA in leukemic cells. These findings suggest that DIC in APL patients with relapse might not be caused only by TF and t-PA and thus should be treated with different therapy from patients with initial onset of APL.
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PMID:Decreased tissue factor and tissue-plasminogen activator antigen in relapsed acute promyelocytic leukemia. 1086 7


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