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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study demonstrated that intravenous infusion of recombinant human soluble thrombomodulin (rhs-TM) could inhibit disseminated intravascular coagulation (DIC) caused by 4 hr infusion of tissue factor (TF) in rats. Extended infusion of TF reduced fibrinogen and platelet counts and elevated serum FDP level. Pretreatment and coinfusion of rhs-TM could block changes of these DIC-parameters without prolongation of APTT. Heparin, which is a potent anti-DIC drug, could also inhibit these changes with extra prolongation of APTT and PT. Thus, these results suggest thrombomodulin prevent DIC less bleeding tendency than heparin.
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PMID:Intravenous extended infusion of recombinant human soluble thrombomodulin prevented tissue factor-induced disseminated intravascular coagulation in rats. 817 1

Endothelium damage is associated with thrombotic risk in a variety of diseases including atherosclerosis, gram negative sepsis, viral infections and neoplastic disease. Therefore, it appears necessary to find a mean for the clinical investigation for such a damage. Among the markers of these cells, thrombomodulin which is a membrane glycoprotein, seems to be of great interest for this purpose. Actually, thrombomodulin is also found in plasma, following an endothelial lesion. Plasma levels of thrombomodulin are increased in a certain number of pathologies associated with endothelium lesion: atheromatous arterial disease, disseminated intravascular coagulation syndrome and also in systemic lupus erythematosus where the levels of plasma thrombomodulin are related to the severity of the pathology. Moreover, previous in vitro studies confirm the fact that the release of thrombomodulin from the endothelial cell membrane occurs during the course of injury by activated leukocytes or hydrogen peroxide. So, one can suppose a prospective interest in the measurement of plasma thrombomodulin as a diagnostic tool for the approach of endothelium damage.
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PMID:Plasma thrombomodulin: new approach of endothelium damage. 820 13

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

We found that patients with thrombotic thrombocytopenic purpura (TTP) have significantly elevated plasma thrombin antithrombin III complex (TAT) and FDP-D-dimer levels, while the plasmin-alpha 2 plasmin inhibitor complex (PIC) level was only slightly increased. The tissue-type plasminogen activator (t-PA) level was increased, but it was well correlated with the plasminogen activator inhibitor-I (PAI-I) level. These findings suggest that hypercoagulable and hypofibrinolytic states coexist in these patients, in contrast to patients with disseminated intravascular coagulation, who exhibit coexisting hypercoagulable and hyperfibrinolytic states. Levels of vascular endothelial cell markers, such as PAI-I, thrombomodulin (TM), and t-PA, were increased at the onset of TTP, but the level of von Willebrand factor (vWF) antigen was not increased. The outcome in TTP patients was correlated with plasma t-PA and TM levels but not with TAT or PIC. These results suggest that vascular endothelial cell markers, such as TM and t-PA, are released from injured or stimulated endothelial cells, reflecting the degree of vascular endothelial damage, and that the main factor in the pathogenesis of TTP is vascular endothelial cell injury.
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PMID:Increased levels of vascular endothelial cell markers in thrombotic thrombocytopenic purpura. 826 13

We examined vascular endothelial cell markers, thrombomodulin (TM), plasminogen activator inhibitor-I (PAI-I), tissue plasminogen activator (t-PA), and von Willebrand factor, in 80 patients with disseminated intravascular coagulation (DIC). The levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC) and FDP-D-dimer were significantly increased both before and after the onset of DIC, but were not correlated with organ failure or prognosis. However, the PIC/TAT ratio was lower in patients with poor prognosis than in those with good prognosis, and it was also lower in those with organ failure than in those without. Plasma TM, PAI-I, and t-PA levels were increased in DIC patients with organ failure or poor outcome, but were not significantly increased before the onset of DIC. We consider that the prognosis of patients with DIC might be related to organ failure or endothelial cell damage and that plasma levels of TM, PAI-I, and t-PA might be useful in the detection of these disorders and in assessing prognosis. A hypofibrinolytic state might enhance organ failure in patients with DIC.
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PMID:Increased vascular endothelial cell markers in patients with disseminated intravascular coagulation. 826 24

A brief explanation of the molecular markers of coagulation, fibrinolysis and endothelial cell activation was done. The clinical significance of markers, such as, soluble fibrin monomer complex, FDP D-dimer, prothrombin fragment 1 + 2, thrombin-antithrombin III complex, plasmin-alpha 2 plasmin inhibitor complex and plasma thrombomodulin in our patients with disseminated intravascular coagulation (DIC) due to abdominal sepsis and malignancy is discussed. The coagulopathy in the DIC patients due to abdominal sepsis had a different aspect from that in the DIC patients due to malignancy. Activation of the coagulation and fibrinolytic systems in sepsis was milder than that in malignancy, despite the decrease of antithrombin III activity in the patients with sepsis. In the patients with sepsis, granulocyte elastase was increased. It was proposed that the coagulopathy was caused not only thrombin formation but also by granulocyte proteinase. It could be expected that the pathophysiology of disseminated intravascular coagulation should be clarified, because of the high sensitivity.
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PMID:[Advancement in the diagnosis of disseminated intravascular coagulation for the surgeon]. 838 85

Thrombomodulin-protein C system plays a very important role for the blood fluidity converting thrombin from a procoagulant protease to an anticoagulant and degrading activated factors Va and V III a. By their properties, both thrombomodulin and protein C may be expected for therapeutic medicines in DIC and some thromboembolic disorders. We reviewed and evaluated the probability of activated protein C and thrombomodulin for DIC treatment. Both appeared to be a very expectant for DIC medicine based on the preliminary clinical or experimental trials. Activated protein C is now under clinical trial in DIC. Recombinant thrombomodulin is also going to start its clinical trial in very near future.
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PMID:[Therapeutic strategy of newly developing medicines for disseminated intravascular coagulation--activated protein C and thrombomodulin]. 838 87

We examined 395 patients with disseminated intravascular coagulation (DIC) divided into two groups: non-leukemic and leukemic. In 58% of the patients as a whole, treatment of DIC resulted in complete or partial remission, while exacerbation and death occurred in 31%. The efficacy of DIC treatment in the non-leukemic group was less than that in the leukemic group, indicating that the outcome of DIC depended, in part, on the underlying disease. We examined hemostatic indicators in relation to DIC score: prothrombin time (PT) ratio, FDP, platelet count, and fibrinogen levels were found to be important indicators for the diagnosis of DIC, but not for Pre-DIC. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PPIC) were significantly increased in pre-DIC. The efficacy of treatment in relation to the DIC score when the treatment was begun showed that greater efficacy was achieved in pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early diagnosis and early treatment are important. On examining the relationship between outcome and hemostatic indicators, we found that the PT ratio and the levels of antithrombin, plasminogen, PPIC, the PPIC/TAT ratio, and thrombomodulin were related to outcome, suggesting that very high consumption of blood coagulation factors, liver dysfunction, hypofibrinolysis, or organ failure caused a poor outcome. Although the outcome in DIC patients may not depend substantially on plasma levels of TAT and fibrin-D-dimer, we can use these indicators to treat DIC patients at an early stage.
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PMID:Outcome of disseminated intravascular coagulation in relation to the score when treatment was begun. Mie DIC Study Group. 857 9

Adult respiratory distress syndrome (ARDS) is a serious complication of disseminated intravascular coagulation (DIC) or multiple organ failure. To determine whether recombinant soluble human thrombomodulin (rsTM) may be useful in treating ARDS due to sepsis, we investigated the effect of rsTM on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats. The intravenous administration of rsTM prevented the increase in pulmonary vascular permeability induced by LPS. Neither heparin plus antithrombin III (AT III) nor dansyl Glu Gly Arg chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, prevented LPS-induced vascular injury. The agents rsTM, heparin plus AT III, and DEGR-Xa all significantly inhibited the LPS-induced intravascular coagulation. Recombinant soluble TM pretreated with a monoclonal antibody (moAb) that inhibits protein C activation by rsTM did not prevent the LPS-induced vascular injury; in contrast, rsTM pretreated with a moAb that does not affect thrombin binding or protein C activation by rsTM prevented vascular injury. Administration of activated protein C (APC) also prevented vascular injury. LPS-induced pulmonary vascular injury was significantly reduced in rats with leukopenia induced by nitrogen mustard and by ONO-5046, a potent inhibitor of granulocyte elastase. Results suggest that rsTM prevents LPS-induced pulmonary vascular injury via protein C activation and that the APC-induced prevention of vascular injury is independent of its anticoagulant activity, but dependent on its ability to inhibit leukocyte activation.
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PMID:Recombinant human soluble thrombomodulin reduces endotoxin-induced pulmonary vascular injury via protein C activation in rats. 860 7

To investigate the relationships between tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1 beta), soluble thrombomodulin (TM), and disseminated intravascular coagulation (DIC) in patients with systemic inflammatory response syndrome (SIRS), twenty-nine SIRS patients were classified into three groups; 4 patients without DIC, 8 DIC patients who recovered, and 17 DIC patients who did not recover. Serum TNF, IL-1 beta, and soluble TM were measured on the day of the diagnosis of SIRS, and also on the 1st, 3rd, 5th days. All of the DIC patients had multiple organ dysfunction syndrome (MODS) and the number of the dysfunctioning organs showed significant differences between the groups (p = .0017). All of the patients who did not recover from DIC died. The serum soluble TM level was higher in the patients without DIC recovery than in either the DIC recovery patients or the non DIC patients throughout the study period. In DIC patients who did not recover, there were significant correlations between soluble TM and TNF (r2 = 0.205, p = .0003) or IL-1 beta (r2 = 0.157, p = .0036). In conclusion, the DIC being associated with endothelial injury is an important pathogenetic factor for MODS and is a main determinant of the outcome of SIRS patients. TNF and IL-1 beta might be involved in the cause of this endothelial injury. The soluble TM is a good predictor of organ dysfunction and also of a poor prognosis.
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PMID:Cytokines, soluble thrombomodulin and disseminated intravascular coagulation in patients with systemic inflammatory response syndrome. 861 Feb 80


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