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)

We had rare opportunities to examine changes in fibrin degradation products (FDP)-D-dimer (DD), thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PIC) and other coagulation parameters during the clinical courses of living-related partial liver transplantation (LRPLT). In seven out of eight recipients without severe rejection and/or disseminated intravascular coagulation (DIC), FDP-DD values reached their maximum at 5 to 10 days after transplantation, then gradually decreased. On the other hand, TAT values rose to the maximum at anhepatic or reperfusion phase of liver transplantation. These data represent hypercoagulation in consequence of tissue thromboplastin activation after extensive operation. Changes in PIC, tissue-type plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) in the clinical course of case 1 suggested that fibrinolysis was suppressed by relatively elevated level of PAI-1 around the operation, but thereafter was adversely accelerated by relatively lower levels of PAI-1. In comparison with patients with DIC, TAT was much higher but PIC was significantly lower in recipients of LRPLT. These findings indicated that marked hypercoagulation and mild to moderate hyperfibrinolysis occurred in recipients of LRPLT.
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PMID:[Changes in coagulation parameters during the clinical courses of recipients of living-related partial liver transplantation]. 747 43

Defibrotide is a polydeoxyribonucleotide-derived anti-ischemic drug with multiple sites of action involving both plasmatic and cellular targets. This agent has been demonstrated to produce profibrinolytic, cytoprotective, and vaso-facilatory actions. Since monocytes are increased in the mediation of some of the pathophysiologic responses seen in ischemic disorders, the functional properties of these cells were investigated in experimental conditions to evaluate their behavior during resting and stimulated states. Defibrotide was supplemented in these systems to determine its modulatory action. In this investigation Defibrotide was found to decrease the PAI-1 levels and may indicate that this may be the mechanism for its profibrinolytic actions. Defibrotide was also found to reduce the procoagulant activity of monocytes in these experimental settings. Both PAI and procoagulant factors play an important role in the pathophysiology of inflammation, DIC, and ischemia. Defibrotide induced reduction of these two factors represents the mechanism whereby this agent produces its therapeutic action.
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PMID:Defibrotide reduces monocyte PAI-2 and procoagulant activity. 766 Jan 47

Protein C (PC) is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating thrombosis and fibrinolysis by inhibiting not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). In the present study we examined the effects of human APC on tissue thromboplastin-induced disseminated intravascular coagulation (DIC) in rabbits and compared them with those of heparin. Both APC (300-3000 U/kg) and heparin (100-300 IU/kg) inhibited the decreases in platelet count and fibrinogen level equally. APC improved the prolonged bleeding time, but heparin aggravated bleeding with potent prolongation of activated partial thromboplastin time (APTT). Furthermore, in APC-treated animals, fibrin deposition in glomeruli was less than in heparin-treated animals. This result that APC accelerated local fibrinolysis by neutralizing PAI-1. From our findings, we concluded that APC can improve both coagulation and fibrinolysis in a DIC model and should be useful for the clinical remedy of DIC without having an adverse side effect like a bleeding tendency.
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PMID:Characteristic effects of activated human protein C on tissue thromboplastin-induced disseminated intravascular coagulation in rabbits. 787 94

Plasma levels of tissue-type plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor-1 antigen (PAI-1:Ag), the active form of PAI-1 (active PAI) and t-PA.PAI-1 complex (PAI-C) were analyzed in 7 patients with disseminated intravascular coagulation (DIC) syndrome. The levels of t-PA:Ag and PAI-C decreased after amelioration of DIC in 6 patients whose underlying disease improved, but their PAI-1:Ag and active PAI showed various fluctuations. The levels of t-PA:Ag and PAI-C showed a good correlation of r = 0.885. The levels of t-PA:Ag or PAI-C showed an inversed correlation with platelet counts, and correlations with the levels of plasmin.alpha 2PI complex, D dimer and E fragments of FDP. It was considered that plasma levels of PAI-C reflected levels of t-PA released from the endothelial cells, which was related to acceleration of fibrinolysis in DIC patients with improved underlying disease. On the other hand, these levels remained high in a patient whose underlying disease did not improve after recovering from DIC. It was considered that the stimulation of endothelial cells by cancer cells continued to exert an effect.
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PMID:[Fluctuations of tissue-type plasminogen activator.plasminogen activator inhibitor-1 complex in patients with DIC]. 806 36

We measured various coagulable factors and molecular markers in plasma and serum in the disease group including DIC, DIC suspect, thrombosis, acute myocardial infarction, angina pectoris, sepsis, malignant tumor and type II diabetes and the healthy subject group, and surmised the intravascular coagulative-fibrinolytic activity in each disease group compared with the healthy group. Additionally we selected parameters useful for early detection of the pre-thrombotic state and hypercoagulable state. As a result, of the parameters for the coagulative system, those considered useful were the assay of soluble fibrin monomer complexes using the synthetic substrate (FM.Oita), assay of soluble fibrin monomer complexes using HPLC(SFMC.Oita) and thrombin-anti-thrombin III complex (TAT) in this order. Of the parameters for the fibrinolytic system, those considered useful were FDP assay using ELISA (FDP.Oita) and plasmin-alpha 2 plasmin inhibitor complex (PIC). This FDP.Oita had a considerably high detection sensitivity compared with the FDP assay (Diayatron Co.) using the latex photometric immunoassay which has been commercially available. When measurement was made with plasma and serum in the subject disease group as the sample by the high sensitivity assays mentioned above, it was made clear that both the coagulative activity and fibrinolytic activity are increased, albeit with some differences in intensity, in all the disease groups compared with the healthy group. In order for the hypercoagulable state and pre-thrombotic state to be detected, it is important to know the balance between the coagulative activity and fibrinolytic activity. According to the results of the present experiment, a significant directly proportional correlation was recognized between FM.Oita and FDP.Oita and between TAT and FDP.Oita. Therefore, examination of these ratios will be a more detailed indicator of coagulative-fibrinolytic activity than the TAT/PIC ratio, PAI-1/TPA ratio and ATIII/alpha 2 PI ratio hitherto in use. If useful molecular markers such as FM.Oita are measured over time in various cases and these data are compiled and analyzed statistically, it will not be long before the criteria for the hypercoagulable state and pre-thrombotic state are established.
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PMID:[Molecular marker for detecting hypercoagulable state]. 810 79

The clinical relevance of determination of plasma antithrombin III(ATIII) and alpha 2-plasmin inhibitor (alpha 2 PI) activities in patients with disseminated intravascular coagulation (DIC) was analyzed. Although the plasma ATIII activity was decreased in patients with DIC, no significant correlation was observed between plasma level of ATIII and that of thrombin-antithrombin III complex or prothrombin fragment 1+2. The extent of the decrease of ATIII in DIC was the most marked in cases associated with septicemia. The plasma level of ATIII in septicemia without DIC was significantly lower than that in DIC cases without septicemia, suggesting that the decrease of ATIII level could not be related to the pathophysiology of DIC, but to that of septicemia. The plasma half-life of ATIII in septicemia without DIC was significantly shortened in the absence of the increase of TAT level, suggesting that the extravasation of ATIII might be induced probably due to the endothelial damage in septicemia. The alpha 2-Plasmin inhibitor level was decreased in DIC patients. The decrease was the most marked (lower than 60% of normal) in patients with excessive fibrinolysis in which fibrinogen degradation was induced. The plasma level of alpha 2PI was significantly higher in the DIC cases with septicemia than in those without septicemia. The ATIII/alpha 2PI ratio was significantly lower in DIC cases with septicemia than in those with solid tumor or acute leukemia. Moreover, the ATIII/alpha 2PI ratio was significantly lower in MOF cases than in non-MOF cases in septicemia. The mortality of the MOF cases did not correlate with the ATIII/alpha 2PI ratio, but with the plasma level of PAI-1, suggesting that the decrease of ATIII/alpha 2PI ratio might not reflect the irreversible endothelial cell damage. Based on these observations, the calculation of ATIII/alpha 2PI in DIC patients would provide the following information; (1) a low ATIII/alpha 2PI ratio (less than 0.6) was frequently observed in septicemia, which could be related to the occurrence of organ dysfunction; (2) a high ATIII/alpha 2PI ratio (higher than 1.0) with the marked decrease of alpha 2PI level (lower than 60% of normal) suggests the occurrence of excessive fibrinolysis in which anti-fibrinolytic therapy should be considered when clinical bleeding was present; (3) The ATIII/alpha 2PI ratio near 1.0 was observed in DIC associated with the pathological conditions other than described above, such as solid tumors, in which the coagulation and fibrinolysis was almost equally activated.
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PMID:[Clinical relevance of determination of plasma ATIII and alpha 2 PI activities in patients with DIC--application of the molecular markers for the analysis of pathophysiology of DIC]. 810 83

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

The bleeding diathesis in patients with acute promyelocytic leukemia (APL) is generally attributed to disseminated intravascular coagulation (DIC), initiated by the release of procoagulant activity from leukemic cells. Primary fibrinogenolysis, mediated by the release of leukocyte proteases, may also contribute to this disorder. We analyzed coagulation parameters in 15 non-septic APL patients. Before treatment, there was evidence of thrombin activation with DIC: increased levels of circulating thrombin-antithrombin III complexes, prothrombin fragments 1 + 2 and D-Dimer complexes. This DIC syndrome was probably limited, since no prothrombin time decrease, no significant factor V consumption, and normal levels of coagulation inhibitors (antithrombin III and protein C) were observed in APL patients when compared to normal controls. In this context, marked hypofibrinogenemia suggested primary fibrinogenolysis as the predominant etiology. Despite normal or high tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) antigen levels, the plasma PAI-1 activity and the formation of tPA/PAI-1 complexes were lower in APL patients than in normal controls, suggesting a proteolytic degradation of PAI-1, not able to complex tPA. Two other fibrinolytic inhibitor molecules (alpha-2 plasmin inhibitor antigen and histidine-rich glycoprotein antigen) were also significantly reduced, as well as the two subunits of fibrin stability factor XIII, although only subunit A is known to be susceptible to thrombin action. Evidence of degraded forms of von Willebrand factor in the plasma suggested an extended proteolytic activity. Four patients treated with all-trans-retinoic acid (ATRA) as a single differentiating agent were studied serially. A dissociation between these two syndromes--DIC and fibrinogenolysis/proteolysis--was observed. The rapid correction of the lysis markers contrasted with a more prolonged persistence of the procoagulant activity. We observed persistently high elastase/alpha 1-proteinase inhibitor complex levels during ATRA therapy, despite progressive correction of all lysis markers. Thus, the release of elastase from promyelocytic leukemic cells is probably not the only determinant of the fibrinogenolytic/proteolytic syndrome. In summary, the present findings provide new arguments for the association of DIC and proteolysis syndromes in APL-associated coagulation disorders. Further prospective studies are needed in order to confirm the persistence of thrombin activation in course of ATRA therapy.
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PMID:Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. 841 75

The main cause of DIC (disseminated intravascular syndrome) is contact of tissue factor with circulating blood. The main symptoms of DIC are bleeding diathesis caused by consumption coagulopathy and organ dysfunction related to circulatory disturbances due to multiple thrombi. However, the symptoms of DIC differ according to degree of fibrinolysis which is characterized by causal disease of DIC. Usually, enhanced fibrinolysis does not cause organ failure but hemorrhagic diathesis, while impaired fibrinolysis does not cause severe bleeding but organ dysfunction. In almost all cases of acute leukemia and in some cases of solid cancer with DIC, hyperfibrinolysis is common. In cases of severe infection with DIC, impaired fibrinolysis due to abnormal elevation of plasminogen activator inhibitor-1 is frequently seen.
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PMID:[Disseminated intravascular coagulation--pathophysiology]. 843 9


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