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)

Presence of chronic DIC (disseminated intravascular coagulation) eliciting an impeded blood coagulation has been postulated of late as one of the etiology causing toxemia of pregnancy, for which studies have been immunologically made. These theories remain unestablished. In this regard, the role of complement in blood coagulation has been noted, and their correlation is being elucidated. The author introduced a concept of complement to etiological theory of an impeded blood coagulation origin, by which toxemia of pregnancy was studied with emphasis placed on their correlation. The results obtained are as follow: 1) Thrombin and thromboplastin allowed in vitro to decreases the potency of complement, and the lowering also was seen even in the case of simultaneous supplement of urokinase and plasminogen. 2) The decrease also was periodically seen in rabbit's DIC experimentally made. 3) An increase in CH50, C3, C4, and factor B of normal pregnancy were of significance when compared with those of the control (p less than 0.001), while C1 inactivator decreased significantly (p less than 0.001). 4) CH50 was 52.2 +/- 2.4U/ml in severe toxemia, a decrease being of significance (p less than 0.01) as compared with that in third trimester of normal pregnancy. Those other parameters which tended to decrease included hemolytic activity of alternative pathway (AP-CH50), C4, and factor B except C1 inactivator with a trend being high.
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PMID:[Studies on relationship between complement and blood coagulation system in toxemia of pregnancy (author's transl)]. 706 48

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis utilizing a large pore gel showed that human fibrinogen (Fbg) in plasma resolved into 3 components which were tentatively designated as high molecular weight Fbg (HMW), low molecular weight Fbg1 (LMW1) and low molecular weight Fbg2 (LMW2) in order of their electrophoretic mobilities. Their estimated molecular weight were 360,000, 325,000 and 290,000 respectively. In normal plasma the ratio of HMW: LMW1: LMW2 was 71: 27: 2. Subunit chain analysis of Fbg species suggests that one of the A alpha chains in the predominant type of LMW1 is an A alpha remnant designated as A alpha', the molecular weight of which is about half that of the A alpha chain of HMW. The subunit chain formulas for the major forms of HMW and LMW1 are considered as (A alpha/1, 2)2 (B beta)2 (gamma)2 and (A alpha/1, 2) (A alpha') (B beta)2 (gamma)2 respectively. Although it is widely accepted that limited proteolysis of A alpha chain by plasmin might be the cause of Fbg heterogeneity, the conversion of HMW to LMW1 was not observed in the earliest stage of fibrinogenolysis induced by urokinase. However incubation of plasma induced the conversion of HMW to LMW1, even when t-aminomethyl-cyclohexane carboxylic acid or heparin was added to the plasma. These findings suggest that an unknown mechanism independent of plasmin or thrombin is responsible for the Fbg heterogeneity in blood. Clinically it is noticeable that the relative amount of LMW1 decreased markedly in disseminated intravascular coagulation (DIC). Animal models of DIC also exhibited essentially the same Fbg heterogeneity pattern as observed in DIC patients, when the levels of Fbg were recovering after the consumption caused by intravascular coagulation. In DIC it is considered that the consumption and compensatory production of Fbg results in the relative increase of HMW which is the freshly synthesized Fbg.
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PMID:[Studies on fibrinogen heterogeneity in disseminated intravascular coagulation]. 717 13

The importance of the anticoagulant properties of protein S is illustrated by the high incidence of thromboembolic events in individuals with protein S-deficiency. A 7 year old girl was hospitalized with purpura-like bruises and lesions on both thighs after she had suffered from febrile infection. A subsequently developing thrombosis of the left V. femoralis was treated successfully with urokinase. Haemostaseological investigations showed no signs of disseminated intravascular coagulation. However, isolated severe degradation or all protein S-components due to the presence of a circulating autoantibody to protein S was found. After several months the antibody was detectable not any more, activity and antigens of protein S were normal.
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PMID:[Severe acquired protein S deficiency with thrombophlebitis after febrile infection in a 7-year-old girl]. 762 27

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

Coagulopathy is a well recognised complication of peritoneovenous shunting for ascites. The relative contributions of primary fibrinolysis and disseminated intravascular coagulation remain controversial. Plasminogen activating activity was significantly lower in malignant ascites (n = 10, median < 0.02 (range < 0.02-1.26) IU/ml) than in alcoholic ascites (n = 10, 1.07 (0.30-1.49) IU/ml) (p < 0.05). Fibrinolytic activity was determined by a balance between tissue plasminogen activator and plasminogen activator inhibitor-1. There was no significant difference between the two groups in the concentration of tissue plasminogen activator (34 (12-64) ng/ml in malignant ascites v 29 (12-43) ng/ml in alcoholic ascites), but the concentration of plasminogen activator inhibitor-1 was significantly higher in malignant ascites (736 (213-1651) ng/ml) than in alcohol ascites (29 (12-43) ng/ml) (p < 0.05). Malignant ascites contained significantly higher concentrations of urokinase (0.7 (< 0.1-1.3) ng/ml v 0.2 (< 0.1-0.6) ng/ml in alcoholic ascites) and plasminogen activator inhibitor-2 (33 (< 6-140) ng/ml v 9 (< 6-28) ng/ml alcoholic ascites). The plasminogen activating activity of alcohol ascites may lead to primary fibrinolysis after peritoneovenous shunting. The considerably lower activity found in malignant ascites may explain why coagulopathy after shunting is less pronounced in this group of patients.
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PMID:Fibrinolytic activity of ascites caused by alcoholic cirrhosis and peritoneal malignancy. 817 65

Patients with acute promyelocytic leukemia (APL) are at high risk for the development of life-threatening thrombotic and hemorrhagic complications, particularly during induction chemotherapy. This propensity has been attributed to the release of tissue factor (TF)-like procoagulants from the leukemic cells leading to disseminated intravascular coagulation (DIC). However, recent data suggest that the pathogenesis of the coagulopathy is more complicated and may involve activation of the generalized proteolytic cascade resulting in either clotting and/or excessive fibrinolysis. Furthermore, controversy exists regarding the mechanism(s) responsible for the activation of either clotting or fibrinolysis. The malignant promyelocyte may act directly to activate coagulation and/or fibrinolysis. Alternatively, reactive inflammatory cells, which express procoagulant and/or profibrinolytic activities may play an essential role. A third possibility may involve endothelial cell expression of mediators with procoagulant/profibrinolytic properties. Putative profibrinolytic mechanisms include the release of urokinase-type and tissue-type plasminogen activators, decreases in plasminogen activator inhibitor-1 and 2, and decreases in alpha-2 plasmin inhibitor. Putative procoagulant mechanisms include the release of tissue factor, Cancer Procoagulant, or cytokines such as interleukin-1, tumor necrosis factor and vascular permeability factor. Putative anticoagulant mediators include annexins, a group of proteins in human tissue which bind phospholipids and have anticoagulant activity, which have been reported in patients with APL. The current treatment of APL is rapidly evolving because of the efficacy of all-trans retinoic acid (ATRA). All-trans retinoic acid promotes terminal differentiation of leukemic promyelocytes leading to complete remission in the majority of patients with APL with rapid resolution of the coagulopathy. Although the mechanism by which this occurs has not been established, preliminary data suggest that ATRA blocks the downregulation of the thrombomodulin gene and the up-regulation of the tissue factor gene induced by tumor necrosis factor. Since APL is a relatively uncommon disorder, the collaboration of cooperative oncology groups will be important to study patients receiving ATRA or conventional chemotherapy to further elucidate the mechanism(s) of the coagulopathy.
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PMID:New insights into the pathogenesis of coagulation dysfunction in acute promyelocytic leukemia. 822 Jan 53

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

The sole administration of urokinase causes no initial prolongation of activated partial thromboplastin time (A-PTT), but thereafter produces serious progressive prolongation of A-PTT; it also causes a progressive, severe decrease in fibrinogen levels and alpha 2-plasmin inhibitor activity by depletion. The antithrombogenicity of urokinase is not caused by prevention of blood coagulation system activation by antithrombin effect, but by secondary fibrinolysis by plasmin. Consequently, the administration of urokinase as a sole anticoagulant results in activation of coagulation and fibrinolysis, and, as a result, induces disseminated intravascular coagulation. Therefore, it is concluded that administration of urokinase is an inadequate anticoagulation therapy unless it is combined with other antithrombin agents.
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PMID:Danger of urokinase as an anticoagulant with left ventricular assist devices. 857 15

Previous work has shown that disseminated intravascular coagulation (DIC) may produce multiple organ failure, including adult respiratory distress syndrome, by obstruction of visceral micro circulation by microclots DIC can be produced by sepsis. This study tests the ability of a plasminogen activator to prevent death from an intravenous injection of killed Escherichia coli by causing lysis of the microclots. Subjects were two groups of 8 pigs each with body weight of 60-70 lbs. Killed Escherichia coli were injected IV in 16 pigs. Invasive monitoring was used to record physiologic data during the 5.0-hr experimental period. Urokinase injected 20 min after the injection of Escherichia coli organisms significantly prevented mortality, acidosis, and development of blood incoagulability. We conclude that plasminogen activator can significantly prevent fatal Escherichia coli (septic) shock without causing bleeding.
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PMID:A new approach to the treatment of experimental septic shock. 865 1

Coagulation and fibrinolysis factors were studied in six patients after local thrombolysis with urokinase (720,000 IU). Transient abnormalities, such as prolonged prothrombin time, decreased plasminogen and alpha 2-antiplasmin activities, decreased fibrinogen, and increased fibrin degradation products were seen on the day after thrombolysis, but tended to return to the normal range on the 4th day except for one patient who suffered from disseminated intravascular coagulation. Antithrombin III activity did not change so much. Therefore, the dosage of urokinase should be as low as possible to prevent fluctuations in the coagulation and fibrinolysis system.
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PMID:Coagulation and fibrinolysis study after local thrombolysis of a cerebral artery with urokinase. 871 52


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