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)

Thrombomodulin (TM) is an endothelium-associated glycoprotein that converts thrombin from a procoagulant protease to an anticoagulant. Thrombin, a key enzyme in thrombus formation, binds to TM molecules on endothelium with very high affinity. After binding to TM, thrombin fails to act on the coagulation factors and platelets, and its ability to activate protein C is enhanced more than 1000-fold. We expressed soluble recombinant TM (rTM) in CHO cells and evaluated its antithrombotic effect on thrombin-induced thromboembolism in mice and lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats. Thrombin injection into mouse caused acute thromboembolism resulting instantaneous death, however preinjection of rTM neutralized the lethal effect of thrombin in a dose-dependent manner. Soluble rTM also improved the consumption of fibrinogen and platelets in experimental DIC-rats induced by LPS. The effect of rTM was confirmed in histologically. These data suggest that rTM may have a therapeutic effect on thrombosis or DIC in human.
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PMID:[Therapeutic evaluation of recombinant thrombomodulin]. 133 21

Tissue factor pathway inhibitor (TFPI) is the factor Xa-dependent inhibitor of the factor VIIa/tissue factor complex. The plasma concentration of this 276 amino acid, 40 kDa glycoprotein is normally about 100 ng/ml. There are three intravascular pools of TFPI: 50-90% is on the endothelium, 10-50% is in plasma and less than 2.5% is in platelets. The TFPI in plasma is mainly associated with lipoproteins-only about 5% is free TFPI. The lipoprotein-associated TFPI seems to be of less anticoagulant effect than the free TFPI. Both unfractionated heparin, low-molecular-weight heparins and pentosan polysulphate induce release of TFPI after intravenous injection, whereas dermatan sulphate does not. The interactions with TFPI account for a considerable amount of the anticoagulant effect of heparin. Studies have shown increased TFPI levels in plasma from patients with advanced malignancy and in subjects with fatal DIC or septicaemia. The reason for this is unknown. For measuring the anticoagulant activity of TFPI in plasma, end-point or antigen assays may be less useful than the clotting assay with dilute tissue factor. Animal studies indicate that the main physiological role of TFPI is the inhibition of small amounts of tissue factor. TFPI is probably essential for a normal haemostatic balance.
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PMID:The present status of tissue factor pathway inhibitor. 142 Aug 19

Thrombomodulin (TM) is a constituent glycoprotein of endothelial cell membrane, and soluble TM is present also in plasma and urine. It was revealed by experiments using cultured HUVEC in vitro that TM is released from endothelial cell membrane not with monensin, thrombin, fibroblast growth factor, interleukin-1 or endotoxin, but with H2O2 or endotoxin-treated granulocytes. And the release was suppressed by the coexistence of gabexate mesilate or superoxide dismutase. It was suggested that soluble TM was released from endothelial cell membrane by its injury and digested to multiple molecular forms by endogenous and granulocytic protease(s). TM level in circulation is increased in cases of SLE, MCLS, diabetic angiopathy. It was increased in cases of overt DIC and decreased to the normal level when the patient was recovered from DIC. TM level in circulation was also increased in cases of decompensated liver cirrhosis and markedly in cases of renal insufficiency. It was concluded that plasma TM is a parameter reflecting endothelial injury due to inflammation or metabolic disorders of vascular system. But the interpretation of increased plasma TM was difficult when renal insufficiency was complicated.
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PMID:[Soluble thrombomodulin: a specific parameter of endothelial injury]. 185 Dec 35

The paraneoplastic syndrome (PNS) is an association of symptoms and signs not directly related to the site or local manifestations of a malignant tumor or its metastases. Hematologic abnormalities as PNS include erythrocytosis, anemia, neutrophilia, neutropenia, eosinophilia, thrombocytosis, thrombocytopenia, venous thromboembolism and disseminated intravascular coagulation (DIC). These abnormalities are, by and large, due to the production of biologically active growth factors, hormones or as yet unidentified "humors" by the tumor. As our understanding of growth factors controlling hematopoiesis has increased in recent years, the biologic basis of hematologic PNS are better understood. For instance, tumor-associated neutrophilia is now known to be caused by the production of G-CSF by the tumor. The mechanism by which tumor causes thromboembolism have also been extensively investigated. Cancer cells induce platelet aggregation both in vitro and in vivo. Platelet aggregating material has been isolated and partially characterized from tumor cells. The involvement of platelet glycoprotein II b/IIIa in the tumor-platelet interaction has also been shown. Malignant cells contain a unique procoagulant, cancer procoagulant A, that directly activates factor X. Together with tissue factor, this procoagulant appears to have been contribute to a high incidence of thromboembolism in cancer patients. Better understanding of hematologic PNS is important for clinical care of the patients with cancer.
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PMID:[Paraneoplastic syndrome hematologic abnormalities]. 200 36

The bleeding disorder of hemophilia A currently treated by replacement therapy of the missing coagulation factor, factor VIII, is frequently complicated by the development of neutralizing antibodies. The therapeutic potential of attenuated forms of the lipid-associated glycoprotein tissue factor, a known initiator of coagulation, was investigated as a factor VIII-by-passing activity. The protein moiety of tissue factor (Apo-TF) was partially purified and exhibited minimal procoagulant activity before relipidation in vitro. In pilot studies, Apo-TF injection into rabbits previously anticoagulated with an antibody to factor VIII was found to have a procoagulant effect. The efficacy of the material was further demonstrated when injection of Apo-TF in hemophilic dogs resulted in a normalization of the cuticle bleeding time. Little or no change in the blood parameters associated with disseminated intravascular coagulation was observed at lower doses, although mild to moderate effects were seen at higher doses. These data suggest a novel role for Apo-TF preparations as a potential therapeutic agent for hemophiliacs with antibodies to factor VIII once the potential thrombogenicity of such materials is evaluated.
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PMID:Factor VIII-bypassing activity of bovine tissue factor using the canine hemophilic model. 313 99

Fibronectin (FN) is a glycoprotein whose plasma concentrations are reduced in many pathological conditions. In patients with hemoblastosis plasma FN was correlated with some clinical and biological parameters (stage of the disease, hepatosplenomegaly, infections and DIC), in order to assess its value as a tumor marker. The results suggest a poor relationship between FN levels and the course of the disease. However, the behaviour of the protein in relation with treatment was dynamic.
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PMID:Plasma fibronectin in hemoblastosis. 345 31

Low plasma levels of the opsonic glycoprotein fibronectin (Fn) have been suggested to imply an impaired host defense against sepsis. However, the mechanism(s) behind Fn depletion in sepsis are obscure. We measured the Fn plasma concentration in 32 patients 12 to 24 h after the diagnosis of septic shock. Although the average plasma level was low (214 +/- 80 [SD] mg/L) compared to that of a reference material (p less than .001), the range was great (60 to 403 mg/L). A multivariate analysis of some possible influencing factors showed significant (p less than .01) positive correlations to the prothrombin level (r = .62) and the amount of insulin infused per 24 h (r = .63). The relationships to disseminated intravascular coagulation-related variables, hemodilution, and outcome were weak. Cryoprecipitate was infused into 16 patients; Fn levels increased by 52 +/- 18% of the expected increase. The most severely ill patients displayed the lowest rates of increase. The postinfusion decrease in Fn plasma concentration indicated that the plasma half-life of cryoprecipitate Fn was about 25 h. The results support the concept that decreased Fn synthesis, probably in the liver, is the major reason for Fn depletion in sepsis, rather than an increased rate of consumption.
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PMID:Plasma fibronectin levels in sepsis: influencing factors. 367 61

Heparin cofactor II (HCII) is a glycoprotein in human plasma which inactivates thrombin rapidly in the presence of heparin or dermatan sulfate. We have developed a functional assay for HCII in which inhibition of thrombin by plasma is determined in the presence of dermatan sulfate. The assay is specific for HCII by the following criteria: (a) under the conditions of the assay, 125I-thrombin forms complexes in plasma which comigrate with the thrombin-HCII complex during sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE); (b) activity detected by the assay is decreased in plasma absorbed with monospecific antibodies against HCII; and (c) purified antithrombin III (ATIII) is unreactive in the assay system. Addition of Polybrene to the assay permits determination of HCII activity in samples containing less than or equal to 12 U/mL of heparin. The range of HCII concentrations in normal individuals is 1.2 +/- 0.4 mumol/L (mean +/- 2 SD, n = 34). HCII activity was determined in 54 consecutive patients undergoing evaluation for the possibility of disseminated intravascular coagulation (DIC). Ten of the 11 patients with documented DIC had decreased HCII activity as compared with only 7 of the 43 patients without DIC (chi 2 = 19.3, P less than .0001). The concentrations of HCII and ATIII varied in parallel in most of the patients tested. A significant correlation between decreased HCII activity and decreased serum albumin concentration was also observed in these patients and in eight additional patients with hepatic failure in the absence of DIC. We conclude that HCII activity is decreased in many patients with DIC and hepatic failure.
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PMID:Heparin cofactor II activity in patients with disseminated intravascular coagulation and hepatic failure. 404 18

Precipitation pattern of factor VIII related antigen (VIIIR:AG) with concanavalin A (Con A), a glycoprotein binding lectin, was investigated in normal subjects and patients with a variant of von Willebrand's disease (VWD) and disseminated intravascular coagulation (DIC). Decreased precipitation with Con A was demonstrated in patients with a variant of VWD in which VIIIR:AG showed an increase in electrophoretic mobility on crossed immunoelectrophoresis (CIE). Similar findings were obtained in patients with DIC which revealed normal electrophoretic mobility of VIIIR:AG. This procedure was assumed to be useful for the detection of a qualitative abnormality of the factor VIII protein.
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PMID:Decreased precipitation of factor VIII related antigen with concanavalin A in patients with a variant of von Willebrand's disease and disseminated intravascular coagulation. 677 3

Blood coagulation properties and the level of pregnancy-related alpha-2-glycoprotein were examined in patients with dyshormonal diseases of the sex organs before and during treatment with combined synthetic progestins containing high (0.1 mg) and low (0.05 mg) doses of estrogen. The use of these hormonal preparations led to the development of blood coagulation disturbances such as chronic disseminated intravascular coagulation. A reduction of the estrogen doses contained in the synthetic progestins by 1/2 was found to lessen the degree of those disturbances. During the treatment with the estrogen-containing drugs, the level of pregnancy-related alpha-2-glycoprotein rose. A relationship between the doses of the estrogens (contained in the preparations) and the glycoprotein level was found. It is supposed that the pregnancy-related alpha-2-glycoprotein takes part in the processes of the intravascular coagulation. (author's)
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PMID:[Effect of combined synthetic progestins on blood coagulation properties and alpha 2-glycoprotein content]. 724 9


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