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

Plasma concentration of thrombin-antithrombin III complex (TAT), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-2, D-dimer complex and urokinase-plasminogen activator (u-PA) activity were studied in 30 patients with acute nonlymphoblastic leukemia (ANLL), before and during antileukemic therapy. Fifteen patients showed signs of disseminated intravascular coagulation (DIC), 10 of them classified as M3, 2 as M2 and 3 as M5 subtypes. The initial levels of TAT complex were elevated in all ANLL patients. This increase was more pronounced in patients with DIC (p less than 0.05). TAT increased significantly during the treatment period in all cases. u-PA and PAI-1 levels were elevated but there were no statistically significant differences between patients with and without DIC. PAI-2 levels were below the limit of detection in controls and in patients. However, the initially elevated D-dimer complex levels were significantly higher in DIC cases (p less than 0.01) and they increased during the treatment period. A significant and positive correlation between D-dimer and TAT complex values was found in DIC patients (r = 0.68, p less than 0.001). The high TAT complex and D-dimer levels further increased during chemotherapy treatment strongly suggest a hypercoagulable state with secondary activation of fibrinolysis not severe enough to manifest itself as clinically evident DIC in the majority of cases.
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PMID:Increase in the D-dimer levels during treatment in patients with acute myelogenous leukemia. 142 55

We have studied the activation state of the fibrinolytic system in 39 patients with systemic meningococcal disease (SMD). Patients defined as having fulminant septicemia (n = 13) with high (greater than 700 ng/L) levels of endotoxin (LPS) in plasma and severe coagulopathy, had significantly lower functional levels of plasminogen (P less than 0.05) and alpha-2-antiplasmin (P less than 0.01) and higher antigen levels of plasminogen activator inhibitor 1 (PAI-1) (P less than 0.01), and fibrin degradation products (FDP) (P less than 0.01), but not of PAI-2 (P greater than 0.1) as compared with less severely ill patients (meningitis and meningococcemia) (n = 25). A positive correlation existed between the admission (maximum) levels of LPS and PAI-1 (r = 0.86, P less than 0.0001). Decreasing admission levels of platelets were associated with increasing levels of PAI-1 (r = -0.55, P less than 0.001). After initiation of treatment with antibiotics and fresh frozen plasma, the PAI-1 levels declined rapidly. PAI-1 levels greater than 360 micrograms/L on admission predicted the development of a severe septic shock combined with renal impairment correctly in 12 of 13 patients (92%). None of 25 patients without multiple organ failure had PAI-1 levels greater than 260 micrograms/L. PAI-1 levels greater than 1850 micrograms/L were associated with 100% fatality. The results suggest that in the early phase of fulminant meningococcal septicemia an extensive plasmin generation occurs. On admission, however, high levels of PAI-1 seem to inhibit the plasmin generation, and thereby promote DIC.
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PMID:Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease. 231 89

13-trans retinoic acid (13-trans RA) is an effective inducer of differentiation of acute promyelocytic (APL) cells both in vivo and in vitro. It is used in the induction of remission of patients with APL. We found, by using the promyelocytic NB4 cell line established from a patient with APL, that the induction of differentiation with RA was accompanied by modulation of the plasminogen activation system. The expression of urokinase (uPA) activity was rapidly increased in the growth medium and at the surface of cells treated with RA. The high uPA activity was counteracted both in the growth medium and at the cell surface by an increased plasminogen activator inhibitor (PAI) production and reduction of uPA synthesis. The expression of uPA receptor and PAI-2 were stimulated and persisted at 48 hours from RA addition. The simultaneous induction of CD11b suggests that differentiation results in increased production of both. APL patients often encounter episodes of disseminated intravascular coagulation that are associated with secondary fibrinolytic events. Our results suggest that downregulation of uPA activity results in the decrease of plasmin on the surface of the differentiated cells, which may reduce the occurrence of fibrinolytic episodes of patients with APL.
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PMID:Induction of differentiation of promyelocytic NB4 cells by retinoic acid is associated with rapid increase in urokinase activity subsequently downregulated by production of inhibitors. 814 55

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