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)

The changes in various hemostatic parameters were examined within a period from 7 days before the onset of disseminated intravascular coagulation (DIC) in 114 patients (i.e. in their pre-DIC state). The changes in prothrombin time (PT) ratio and fibrinogen levels were not significant before the onset of DIC. Plasma fibrinogen and fibrin degradation products (FDP) levels before the onset of DIC were high, but these changes were already significant in 110 non-DIC patients examined. Plasma thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer and soluble fibrin monomer (SFM) levels were high before the onset of DIC. In the 110 leukemic DIC patients, the plasma SFM levels were significantly increased 5 days before, the plasma TAT levels were significantly increased 3 days before, and the D-dimer levels were significantly increased 1 day before the onset of DIC. The plasma tissue factor and plasminogen activator inhibitor-I levels were not significantly changed before the onset of DIC. The PT ratio, fibrinogen, FDP, platelet count, antithrombin, D-dimer, and PPIC levels at 7 days before the onset of DIC were not significantly different from the corresponding values in the non-DIC group, although the hemostatic molecular markers SFM, D-dimer, and TAT are useful for the diagnosis of pre-DIC. Plasma thrombomodulin levels were significantly increased in these patients who died, and plasma antithrombin and protein C activities markedly reduced in the patients who died. The outcome of the diseases underlying DIC is related to vascular endothelial cell injuries.
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PMID:Hemostatic molecular markers before onset of disseminated intravascular coagulation in leukemic patients. 970 63

Treatment with intravenous recombinant human interleukin-2 (rh IL-2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate more precisely the role of the endothelium in the generation of IL-2-based side-effects. In nine tumour patients receiving intravenous rh IL-2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increase of the circulating endothelial leucocyte adhesion molecule-1 (cELAM-1) and the vasoconstrictor peptide endothelin-1 (ET-1) was observed (P<0.05), indicating activation of endothelial cells. The simultaneous increase of tissue-plasminogen activator and plasminogen activator inhibitor type-1 during therapy (P<0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolongation of partial thromboplastin time, and the decrease of fibrinogen (P<0.05) suggested the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepatic failure. We concluded that activation of the endothelium mediated by IL-2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation cascade. The increased ET-1 might act as an endogenous counter-regulator of the disadvantageous haemodynamic side-effects induced by IL-2.
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PMID:Activation of endothelium by immunotherapy with interleukin-2 in patients with malignant disorders. 1055

We report the effects of substitution with a virus-inactivated protein C (PC) concentrate in disseminated intravascular coagulation (DIC) in infants and children with meningococcal sepsis associated with purpura fulminans. It was a prospective open-label study. Eight pediatric and adolescent patients age 0.2 to 18.25 years with DIC associated with severe acquired PC deficiency (range 0.02 to 0.48 IU/mL; median, 0.22 IU/mL) in meningococcal septic shock and purpura fulminans were studied. Replacement therapy was initiated with a virus-inactivated PC concentrate with an initial intravenous bolus of 80 to 120 IU/kg followed by 50 IU/kg up to six times per day as an adjunctive therapeutic regimen to otherwise optimal intensive care treatment. After initial PC administration, plasma PC levels rose to normal ranges and were maintained under PC replacement therapy. Improving or even normalizing global hemostatic parameters were assessed in all patients. Markedly elevated plasminogen activator inhibitor type 1 (PAI-1) levels prior to treatment, reflecting a reduced fibrinolytic potential, decreased rapidly under PC substitution. Concomitantly improving signs of purpura fulminans reflected by decreasing size of skin lesions, demonstrated a restoring microcirculation. Six of the eight patients survived. One patient required limb amputation; two patients died because of multiorgan failure. Both presented with a severely low plasma PC activity of 0.02 IU/mL on admission to the hospital. No adverse effects were observed with the PC concentrate administration. It can be concluded that the administration of PC concentrate had a marked benefit on the deranged coagulation status of patients with purpura fulminans and meningococcal septicemia. Normalization or even partial correction of hemostasis as well as improvement of microcirculation accompanied by improving signs of purpura fulminans were demonstrated in all patients.
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PMID:Replacement therapy with protein C concentrate in infants and adolescents with meningococcal sepsis and purpura fulminans. 1063 75

Previous studies suggest that there is a systemic activation of clotting and fibrinolysis in preterm infants with advanced respiratory distress syndrome (RDS). However, there are no data on the hemostatic status in the early stages of the disease; therefore, we studied some of the hemostatic parameters in these patients and made several studies at different times in preterm infants who did or did not develop RDS, using similar protocols. We found normal plasma fibrinogen, protein C, protein S, C4b-binding protein, thrombomodulin, antithrombin III, thrombin-antithrombin III complex, prothrombin fragment 1.2, plasminogen, tissue plasminogen activator, alpha-1 antitrypsin, alpha-2-macroglobulin and protein Z. However, lower D-dimer and higher plasminogen activator inhibitor and von Willebrand factor antigen levels were found within six hours of life in infants who later developed RDS compared to the control group. These findings suggest that disseminated intravascular coagulation is not prominent in the early stages of RDS. Moreover, reduced D-dimer and increased plasminogen activator inhibitor and von Willebrand factor antigen levels are probably related to the abnormalities in the fibrinolytic mechanism due to lung damage in RDS, but further studies are needed to show their pathogenic significance in RDS.
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PMID:Hemostatic system in early respiratory distress syndrome: reduced fibrinolytic state? 1077 Jan 17

We examined various hemostatic molecular markers in patients with disseminated intravascular coagulation(DIC), deep vein thrombosis(DVT), pulmonary embolism(PE), acute myocardial infarction(AMI), cerebral thrombosis(CT) and thrombotic thrombocytopenic purpura(TTP). Global tests were sensitive for DIC but not for pre-DIC. However, hemostatic molecular markers such as soluble fibrin were sensitive for both DIC and pre-DIC. Hemostatic molecular markers were also useful for analysis of DIC in a baboon DIC model. Activated protein C-protein C inhibitor complex and plasminogen activator inhibitor-I were useful for the diagnosis of DVT, PE, AMI or CT. These findings suggests that hemostatic molecular markers are useful for the diagnosis of various thrombotic disorders.
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PMID:[Application of hemostatic molecular markers for diagnosis of thrombosis]. 1081 Aug 74

Protein C 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 coagulation and fibrinolysis by inactivating not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). The aim of the present study was to examine the effect of a human APC product (designated as CTC-111), compared with that of heparin, on the disseminated intravascular coagulation (DIC) induced by lipopolysaccharide (LPS) in rats. LPS (1 mg/kg/h) infusion was performed through a femoral vein for 4 h. One-fifth amount of the total dosage of CTC-111 or heparin was injected into the other femoral vein, followed by a 4-h infusion of the remainder. Both CTC-111 (10,000-100,000 U/kg) and heparin (400-800 IU/kg) inhibited the decrease in platelet count and fibrinogen level equally. The prolonged activated partial thromboplastin time and prothrombin time observed in DIC rats were further elongated in both CTC-111- and heparin-treated rats. But, this prolongation was less in CTC-111-treated rats than in the heparin-treated ones. Heparin inhibited the increase in fibrin and fibrinogen degradation products more prominently than CTC-111. On the other hand, CTC-111 strongly inhibited the increase in PAI-1 activity but heparin did not. These results suggest that CTC-111 may enhance fibrinolysis through its direct inhibitory effect on PAI-1. The parameters for liver or renal damage, i.e., plasma glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine (Cre) and blood urea nitrogen (BUN), were significantly increased by LPS infusion. Both CTC-111 (100,000 U/kg) and heparin (800 IU/kg) decreased the increase in GOT and GPT levels significantly, whereas neither affected the increase in Cre or BUN. From these results, the activation of the blood coagulation system might partially contribute to the progression of liver damage caused by LPS, and might be less involved in the progression of renal damage in this model. In conclusion, CTC-111 showed both anticoagulant and profibrinolytic activity in the LPS-induced DIC model without excessive prolongation of coagulation time. From these results, CTC-111 is expected to be a useful remedy for DIC without the risk of bleeding.
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PMID:Effect of activated human protein C on disseminated intravascular coagulation induced by lipopolysaccharide in rats. 1105 Jun 97

Lipopolysaccharide-containing outer membrane vesicles (OMV-LPS) which are spontaneously released from Neisseria meningitidis during logarithmic growth were studied for their ability to induce procoagulant (tissue factor), profibrinolytic (urokinase-type plasminogen activator) and antifibrinolytic (plasminogen activator inhibitor-2) factors in purified human monocytes. Cell-associated tissue factor was 5.0-fold (n=5) increased, peaking after 8 h, in the presence of OMV-LPS (1 microg/ml, final concentration). Plasminogen activator inhibitor-2 release from monocytes was maximal after 24 h OMV-LPS (1 microg/ml) stimulation and 13.7-fold (n=5) increased compared to controls; whereas urokinase-type plasminogen activator antigen in culture medium remained uninfluenced by OMV-LPS. In conclusion, these OMV-induced imbalances favor fibrin deposition in the monocyte microenvironment and is probably of great importance in the development of disseminated intravascular coagulation, microthrombosis and organ dysfunction related to fulminant meningococcal septicemia.
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PMID:Outer membrane vesicles from Neisseria meningitidis: effects on tissue factor and plasminogen activator inhibitor-2 production in human monocytes. 1136 30

In this study, we examined changes in the plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tissue-type plasminogen activator (tPA)/PAI-I complex in patients with disseminated intravascular coagulation (DIC) and in those with thrombotic thrombocytopenic purpura (TTP) to investigate the fibrinolytic function and its relation to organ failure. The plasma levels of total PAI-1 and tPA/PAI-I complex were significantly higher in patients with DIC, pre-DIC, and TTP than in those with non-DIC. The plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, thrombomodulin (TM), total PAI-I, and tPA/PAI-I complex were significantly higher in patients with organ failure than in those without organ failure. The plasma levels of total PAI-I and tPA/PAI-I complex were markedly increased in patients with acute leukemia. The plasma levels of total PAI-I, but not those of tPA/PAI-I complex, were significantly increased in patients with sepsis or with solid cancer. In all cases, total PAI-I or tPA/PAI-I complex was not significantly correlated with any hemostatic marker. Measurement of total PAI-I and tPA/PAI-I complex may be useful in the diagnosis of DIC.
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PMID:Plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tPA/PAI-1 complex in patients with disseminated intravascular coagulation and thrombotic thrombocytopenic purpura. 1144 85

To clarify the role of plasminogen activator inhibitor type 1 (PAI-1) in postburn hypercoagulation, we assayed the plasma levels of tissue-type plasminogen activator (t-PA) antigen, total PAI-1 antigen, and total t-PA-PAI-1 complex in 15 burned patients. The total body surface area of the burn injury ranged from 30 to 80%. Serial blood samples were collected from 12 to 168 h following the thermal injury. The plasma t-PA level and the free PAI-1 level increased significantly in the immediate postburn period, and the percent increase in the latter over the values in the healthy controls was much greater than that of the former. The ratio of the concentrations of t-PA-PAI-1 complex to free PAI-1 decreased throughout the 7 postburn days. The fact that the decreases in this ratio clearly showed no dissociation of the euglobulin fraction suggests that the postburn hypofibrinolysis occurred as a result of increased synthesis of PAI-1. On the other hand, changes in several parameters of the coagulation or fibrinolysis system and in plasma thrombomodulin showed that postburn hypercoagulability is associated with secondary hyperfibrinolysis with no evidence of vascular endothelial injury. The paradoxical coexistence of postburn hyper- and hypofibrinolysis is a good reflection of the character of PAI-1, which is a biphasic protein that is both a functional protein and an acute phase reactant. Thus, increased synthesis of PAI-1 may not enhance postburn hypercoagulability to create a coagulation-dominant type of disseminated intravascular coagulation severe enough to trigger multiple organ dysfunction syndrome. In conclusion, increased synthesis of PAI-1 in the initial postburn period reflects an integrated endothelial response to burn stress, and because it is a functional protein, the concentration of free PAI-1 antigen may be an important index for predicting secondary consumption coagulopathy.
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PMID:Elevation of plasma free PAI-1 levels as an integrated endothelial response to severe burns. 1152 50

Studies in experimental models for sepsis, the most common cause of disseminated intravascular coagulation (DIC), have put forward the concept of a procoagulant state that is characterized by thrombin generation exceeding that of plasmin. Convincing evidence indicates that this imbalance between coagulation and fibrinolysis is due to increased levels of plasminogen activator inhibitor type 1 (PAI-1). Levels of this fibrinolysis inhibitor indeed correlate with outcome and severity of multiple organ failure in patients with sepsis, as well as in patients with DIC from other causes. Hence we suggest that PAI-1 constitutes an important target for therapy in patients with DIC.
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PMID:Fibrinolysis in disseminated intravascular coagulation. 1174 Jun 86


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