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)

In disseminated intravascular coagulation (DIC) with acute promyelocytic leukemia (APL) in the absence of severe infection, marked fibrinolysis was noted in comparison with normal levels of antithrombin III, which is a major inhibitor of the coagulation system. Increased plasminogen activator inhibitor-1 (PAI-1) antigen levels in plasma from patients with septicemia decreased the ratio of the plasma clot lysis rate induced by an anti-alpha 2-plasmin inhibitor monoclonal antibody to the tissue-type plasminogen activator (t-PA) concentration. This decrease was not as prominent in plasma from patients with DIC, especially those with APL. To explore the character of PAI-1 in these plasmas, we measured the specific activity of PAI-1 by determining the ratio of active PAI-1 antigen to t-PA-unbound PAI-1 antigen. To calculate the amount of active PAI-1 antigen, the amount of t-PA/PAI-1 complex before and after the addition of a fixed amount of t-PA to the sample was measured by a sandwich solid-phase enzyme-linked immunosorbent assay using anti-PAI-1 and anti-t-PA monoclonal antibodies. The assay to measure total PAI-1 antigen used three monoclonal anti-PAI-1 antibodies and had similar sensitivities to free active, latent, vitronectin-bound and t-PA-bound PAI-1. The specific activity of PAI-1 decreased in patients with DIC (43.7% +/- 30.6%) and in DIC cases with APL (10.3% +/- 6.0%) in comparison to patients with septicemia (83.7% +/- 20.2%) or normal controls (85.8% +/- 27.3%). In DIC associated with APL, degraded forms of PAI-1 were detected in plasma by immunoblotting. These results suggest that a decrease in the specific activity of PAI-1 and an increase in secondary fibrinolysis result in a hyperfibrinolytic state in DIC patients with APL.
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PMID:The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia. 170 94

The pathophysiology of peripheral circulatory disturbance in patients presenting with vibration syndrome was studied from the viewpoint of blood coagulation. Plasma levels of fibronectin (FN), vitronectin (VN), thrombin-antithrombin III complex (TAT), and alpha 2-plasmin inhibitor-plasmin complex (PIC) were measured in 23 subjects who showed no evidence of vibration-induced white finger [VWF(-) group] and in 24 patients who presented with VWF [VWF(+) group]. In the VWF(-) group, plasma FN concentrations were elevated but plasma TAT and PIC levels were within the normal ranges. In the VWF(+) group, plasma FN concentrations were normal but plasma TAT and PIC levels were significantly elevated. In both groups, plasma VN concentrations were similar to those in normal controls. For purposes of comparison, 32 patients presenting with diabetes mellitus were also studied. They were divided into 2 groups, 13 subjects who showed no evidence of angiopathy [complication(-) group] and 19 patients who presented with angiopathy [complication(+) group]. In the complication(+) group, plasma TAT and PIC concentrations were significantly elevated, as in the VWF(+) group. These results suggest that in vibration syndrome, vibration, cold stimulus, or other factors first injure the vascular endothelium, resulting in a rise in plasma FN, and that in the VWF(+) group, augmentation of coagulation and fibrinolysis induces a state of compensated disseminated intravascular coagulation (DIC).
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PMID:Activation of blood coagulation and fibrinolysis in vibration syndrome. 172 Jul 65

Vitronectin, also known as serum-spreading factor or S-protein, mediates cell adhesion and inhibits formation of the membrane-lytic complex of complement and the rapid inactivation of thrombin by antithrombin III in the presence of heparin. Vitronectin is normally present in plasma at a concentration of approximately 300 micrograms/mL. The investigators quantified plasma vitronectin with an enzyme-linked immunosorbent assay and visualized reduced and nonreduced vitronectin by immunoblotting after separation of plasma or serum by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The concentration of plasma vitronectin was markedly reduced in some patients with disseminated intravascular coagulation, especially in those with liver failure; it was near normal in patients with metastatic cancer and acute leukemia. Patients with vitronectin levels less than 40% normal invariably had low fibrinogen and antithrombin III and a prolonged prothrombin time. In both normal and patient plasmas there was heterogeneity in the ratio of the 75,000- and 65,000-mol wt polypeptides of reduced vitronectin: 18% had mostly the 75,000-mol wt polypeptide, 59% had roughly equal amounts of the two polypeptides, and 22% had mostly the 65,000-mol wt polypeptide. This polymorphism is inherited and appears to be due to two alleles that are present with approximately equal frequency. The blotting patterns of vitronectin in reduced and nonreduced plasmas were largely unaltered in plasma of patients with defibrination syndrome, fibrinolysis, liver failure, sepsis, metastatic cancer, and acute leukemia. There was no evidence of fragmentation of vitronectin or formation of the disulfide-bonded complex of vitronectin and thrombin-antithrombin III that is found when blood is clotted. Thus these results corroborate in vitro observations that the liver is the major source of plasma vitronectin, suggest that vitronectin may become depleted during disseminated intravascular coagulation, and define a genetic polymorphism of vitronectin.
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PMID:Plasma vitronectin polymorphism in normal subjects and patients with disseminated intravascular coagulation. 245 67

Radiolabeled antithrombin III (ATIII) was incubated at 37 degrees C with purified vitronectin (VN) or fibrinogen-deficient plasma before thrombin was added to initiate complex formation. Incorporation of radiolabeled ATIII was detected using polyacrylamide gel electrophoresis (PAGE) and autoradiography. The PAGE conditions appeared to be crucial for the detection of VN.TAT complexes. In the absence of SDS, ternary complexes formed instantaneously, whereas in the presence of SDS, only 50% of the TAT was associated with VN after a 60-min incubation. Formation of ternary complexes could be confirmed by gel filtration of the plasma to which thrombin was added. Furthermore, TAT in patient plasmas (disseminated intravascular coagulation and sepsis) was found to bind to heparin-Sepharose, indicating that this endogenously formed TAT was also associated with VN. The amino-terminal region of VN and the thrombin moiety of the TAT complex were found to be responsible for their interaction, which was stabilized by disulfide bridges. These results indicate that in normal plasma all TAT is complexed with VN. This association alters the conformational state of plasma VN, which appears to be responsible for the clearance of thrombin complexes from the circulation.
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PMID:Ternary vitronectin-thrombin-antithrombin III complexes in human plasma. Detection and mode of association. 767 52

Combination treatment with the clotting factors recombinant activated factor VII (rFVIIa), serine protease, and recombinant factor XIII (rFXIII), protransglutaminase, is being explored for haemostatic therapy. We performed a single-dose toxicology study in the cynomolgus monkey, with four dose groups receiving 0.1 + 0.34 mg kg(-1) (group 1), 0.33 + 1.12 mg kg(-1) (group 2), 1.67 + 5.60 mg kg(-1) (group 3) and 5.00 + 16.80 mg kg(-1) (group 4) of a rFVIIa + rFXIII combination. In the three lower dose groups, no clinical, histopathological or blood chemistry changes were observed. In group 4, the animals died at 4 h post-dosing, with histopathology revealing a systemic coagulopathy resembling, but distinct from, disseminated intravascular coagulation. Due to the absence of toxicity warning signs, toxicity biomarkers were identified by a Western blot-based screening of approximately 20 plasma proteins known to be involved in the clotting cascade. Three of the examined proteins were specifically affected by rFVIIa + rFXIII treatment. Fibronectin and fibrinogen exhibited dose-dependent reductions from less than 10% reduction (group 2) to more than 90% reduction (group 4). These reductions were reversible, and specific. For vitronectin, a dose-dependent conversion to the 65-kDa form was found to occur in groups 3 and 4. Thus, fibrinogen, fibronectin and vitronectin represent the first biomarkers for clotting factor toxicity.
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PMID:Preclinical toxicity biomarkers for combination treatment with clotting factors rFXIII and rFVIIa. 1756 47

Disorders of haemostasis and haemocoagulation are often seen in patients with cancer as a part of paraneoplastic syndrome. Thrombotic and/or haemorrhagic complications are the second most common cause of mortality in patients with cancer. The evaluation of the haemostatic parameters of 67 patients with gastric cancer have indicated tendency to thrombophilia and activation of intravascular coagulation, of which 31.3% showed tendency to hypercoagulation and 47.8% disseminated intravascular coagulation (DIC). Only 7.5% of subjects have yielded normal laboratory findings while 5.9% of patients had DIC with remarkable hypocoagulation. Thrombocytosis, platelet hyperaggregability and elevation of beta-thromboglobulin are the indicators of changes in primary haemostasis and elevation of thrombomodulin indicates vascular wall damage. Lower antithrombin III levels, C-protein and S-protein in plasma have indicated lower antithrombotic potential in patients with gastric cancer. It can be concluded that patients suffering from gastric cancer are at higher risk of thromboembolism as for haemorrhagic diathesis (20.1% thromboembolism, 11.94% fatal thromboembolic events vs 5.9 % haemorrhagic diathesis) (Tab. 5, Ref. 22). Full Text (Free, PDF) www.bmj.sk.
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PMID:General changes in hemostasis in gastric cancer. 2019 67