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)

Hemostasiologic effects of intravenous application of Reptilase were investigated in a randomized double blind study in the course of normal abdominal and vaginal hysterectomies. Coagulation factors and thrombocytes were checked before, after, 40 minutes after as well as 24 hours after the operation. Significant shortening of the clot observation time resulted 40 minutes after the injection of 1 ml Reptilase. A small but highly significant decrease of thrombocytes was observed 40 minutes after the end of the operation when Reptilase was injected. Further coagulation screening tests: Quick test, PTT and thrombin time were without statistically differences in both patients groups from the beginning till 24 hours after the operation. A significant decrease in Factor V concentrations resulted 40 minutes after the injection of Reptilase, whereas no changes were seen in the placebo patient group. Too, Factor XIII values and Antithrombin 3 concentrations decreased after the administration of Reptilase. There was no abnormal raise of fibrin-monomers in both groups. Enhanced fibrinolysis with elevated FDP-levels were measured in none of the cases. The administration of Reptilase induced a short lasting augmentation of blood coagulation but without any signs of disseminated intravascular coagulation.
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PMID:[Coagulation factors and thrombocytes after application of Reptilase in the course of gynecologic operations (author's transl)]. 65 62

There is compelling experimental evidence that tissue factor pathway inhibitor (TFPI) exerts important role(s) as a natural anticoagulant. Immunodepletion of TFPI lowers the treshold by which tissue factor (TF) can induce disseminated intravascular coagulation. Conversely, infusion of recombinant TFPI protects against thrombosis and disseminated intravascular coagulation in numerous experimental models. Since TFPI mutants associated with thrombosis have not yet been identified, a definite role of TFPI in coagulation is yet to be assigned. Current research on TFPI is mainly focused on the cell biology of TFPI, on the contribution of TFPI to the anticoagulant action of heparins, and on the role of lipoprotein-associated TFPI. TFPI is produced constitutively in endothelial cells, and is to a great extent bound to its surface. The binding molecule(s) have not yet been characterized, but TFPI is rapidly released by heparin and other negatively charged ions. In other cell lines degradation of TFPI is mediated by the low density lipoprotein receptor-related protein, which may be important for its clearance. In plasma, TFPI contributes strongly to the postheparin anticoagulant effect seen in dilute prothrombin time assays. The effect is probably mediated by redistribution of TFPI. Moreover, in the presence of heparin, antithrombin and TFPI cooperate to inhibit activation of coagulation. Antithrombin abrogates activation of factor VII bound to TF, whereas TFPI inhibits factor VIIa/TF complexes formed. The role of lipoprotein associated TFPI is still essentially unknown, but may play an important role in atherosclerosis.
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PMID:Tissue factor pathway inhibitor (TFPI)--an update. 897 19

Antithrombin (AT) is a single-chain glycoprotein in plasma and belongs to the family of the serpins. It is synthesized in liver parenchymal cells, and its plasma concentration is between 112-140 mg/L. AT is a unique inhibitor of the clotting system and neutralizes most of the enzymes generated during activation of the clotting cascade, especially thrombin, factors Xa and IXa. Equimolar, irreversible complexes are formed between AT and the enzymes. The interaction between AT and the activated clotting factors is at least 1,000-fold increased in the presence of heparins. Heparins bind to multiple sites of the AT molecule resulting in a steric reconfiguration. Heparins contain a specific pentasaccharide unit which is the minimum requirement for AT binding. The glycosaminoglycan (GAG) heparan sulfate found on endothelial cell surfaces also contains this pentasaccharide and can thus "activate" AT. It is believed that much of the physiological inactivation of enzymes by AT occurs on the endothelium, mediated by heparan sulfate. The binding of AT to the GAGs also releases prostacyclin which possesses strong antiinflammatory properties. Deficiencies of AT are inherited or acquired. Only acquired defects due to increased consumption are discussed, most notably AT in DIC, especially DIC in sepsis. During acute DIC, clotting factors and inhibitors are consumed faster than they can be reproduced. This consumption of AT is of great significance in DIC and sepsis, and plasma AT levels predict outcome. AT levels drop early in sepsis and laboratory signs of DIC can already be found in patients with SIRS and early sepsis. The important role of AT in DIC and sepsis is the basis for considering antithrombin concentrates as an additional therapeutic modality.
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PMID:Antithrombin: its physiological importance and role in DIC. 951 76

Several studies have shown that thrombosis and inflammation play an important role in the pathogenesis of Ischaemic Heart Disease (IHD). In particular, Tissue Factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key role in triggering thrombin generation. The aim of this study was to evaluate the TF/Tissue Factor Pathway Inhibitor (TFPI) system in patients with IHD. We have studied 55 patients with IHD and not on heparin [18 with unstable angina (UA), 24 with effort angina (EA) and 13 with previous myocardial infarction (MI)] and 48 sex- and age-matched healthy volunteers, by measuring plasma levels of TF, TFPI, Prothrombin Fragment 1-2 (F1+2), and Thrombin Antithrombin Complexes (TAT). TF plasma levels in IHD patients (median 215.4 pg/ml; range 72.6 to 834.3 pg/ml) were significantly (p<0.001) higher than those found in control subjects (median 142.5 pg/ml; range 28.0-255.3 pg/ml). Similarly, TFPI plasma levels in IHD patients were significantly higher (median 129.0 ng/ml; range 30.3-316.8 ng/ml; p<0.001) than those found in control subjects (median 60.4 ng/ml; range 20.8-151.3 ng/ml). UA patients showed higher amounts of TF and TFPI plasma levels (TF median 255.6 pg/ml; range 148.8-834.3 pg/ml; TFPI median 137.7 ng/ml; range 38.3-316.8 ng/ml) than patients with EA (TF median 182.0 pg/ml; range 72.6-380.0 pg/ml; TFPI median 115.2 ng/ml; range 47.0-196.8 ng/ml) and MI (TF median 213.9 pg/ml; range 125.0 to 341.9 pg/ml; TFPI median 130.5 ng/ml; range 94.0-207.8 ng/ml). Similar levels of TF and TFPI were found in patients with mono- or bivasal coronary lesions. A positive correlation was observed between TF and TFPI plasma levels (r = 0.57, p<0.001). Excess thrombin formation in patients with IHD was documented by TAT (median 5.2 microg/l; range 1.7-21.0 microg/l) and F1+2 levels (median 1.4 nmol/l; range 0.6 to 6.2 nmol/l) both significantly higher (p<0.001) than those found in control subjects (TAT median 2.3 microg/l; range 1.4-4.2 microg/l; F1+2 median 0.7 nmol/l; range 0.3-1.3 nmol/l). As in other conditions associated with cell-mediated clotting activation (cancer and DIC), also in IHD high levels of circulating TF are present. Endothelial cells and monocytes are the possible common source of TF and TFPI. The blood clotting activation observed in these patients may be related to elevated TF circulating levels not sufficiently inhibited by the elevated TFPI plasma levels present.
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PMID:Elevated tissue factor and tissue factor pathway inhibitor circulating levels in ischaemic heart disease patients. 953 Oct 29

Replacement of antithrombin has proved to be effective for treating disseminated intravascular coagulation. The administration of antithrombin is also useful for preventing organ failure in animals challenged with endotoxin or bacteria, and it increases the survival rate of such animals. Since inhibition of coagulation abnormalities by heparin failed to prevent organ failure in animals challenged with bacteria, antithrombin might exert therapeutic effects independently of its anticoagulant effect. These therapeutic mechanisms of antithrombin have been explored by using animal models of septicemia. Antithrombin prevents pulmonary vascular injury by inhibiting leukocyte activation in rats challenged with endotoxin. A higher dose of antithrombin was required to prevent pulmonary vascular injury than was required to inhibit disseminated intravascular coagulation. This preventive effect of antithrombin is mediated by the promotion of endothelial release of prostacyclin, an inhibitor of leukocyte activation. An interaction between antithrombin and heparin-like glycosaminoglycans on the endothelial cell surface appears to be important for this effect. Heparin inhibits such therapeutic effects of antithrombin by preventing it from interacting with the cell surface heparin-like glycosaminoglycans. Since activated leukocytes are of critical importance in patients with sepsis-associated organ failure, this anti-inflammatory activity of antithrombin may explain why it can prevent organ failure as well as coagulation abnormalities in patients with sepsis.
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PMID:Antithrombin prevents endotoxin-induced pulmonary vascular injury by inhibiting leukocyte activation. 966 67

Antithrombin (AT) is an important inhibitor of the coagulation system, acting at many different levels of the coagulation cascade. This inhibitory action is enhanced several-fold by the glycosaminoglycan heparin. AT deficiency can be encountered in hereditary disorders, which are rare, or in acquired conditions, in which there is an excessive consumption of AT. Acquired AT deficiency is a common condition in sepsis, after major trauma or surgery, with or without associated disseminated intravascular coagulation (DIC). In these conditions, low levels of AT have been correlated with a poor outcome due to the development of multiple organ failure. Although supplementation with AT has been shown to attenuate the extent of organ failure in critically ill patients, it has not been possible to significantly improve the survival of these patients by administration of AT. An interesting new approach to AT treatment is based on the hypothesis that AT has specific effects that are independent of the coagulation cascade. Data from cell culture and animal experiments have demonstrated that AT can promote the endothelial production of prostacyclin and may therefore have anti-inflammatory actions. This effect is based on the interaction of AT with glycosaminoglycans in the cell membrane, and is independent of heparin. The role of AT in vessel wall antithrombogenicity is being increasingly appreciated. The concept of neointimal hyperplasia following vascular injury involves thrombin as an important mediator and thus, in addition to the anti-inflammatory effects of AT, new horizons in which AT may have an important role in the prevention of post-traumatic hyperplastic response are also evolving.
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PMID:Antithrombin: facts and new hypotheses. 1010 92

Antithrombin (AT) is the most important inhibitor of the coagulation system. Due to the high cost of AT treatment, there must be rational arguments to justify its use. Established indications for AT substitution include hereditary homozygous AT deficiency in newborn babies and hereditary AT deficiency before or during certain situations, for example, surgery and pregnancy. AT substitution therapy can also be justified in the treatment of complex coagulation disorders, sepsis with disseminated intravascular coagulation and acute thromboembolic events with reduced AT activity. Administration of AT concentrates to patients with nephrotic syndrome or stable hepatopathy is not justified. To achieve an anti-inflammatory effect in patients with sepsis, it is thought that above-normal levels of AT activity (> 140% of the normal level) are probably needed. Although currently available data on the effect of AT in the treatment of sepsis are insufficient, results from controlled studies will soon become available and will show whether sepsis is an indication for AT substitution.
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PMID:Antithrombin substitution therapy. 1010 95

Antithrombin (AT) is the most important inhibitor of activated coagulation enzymes. Deficiency of this protein can be a congenital defect. Different types have been described with a diminution of the entire molecule as well as diminution of activity only with normal concentration and normal activity and concentration but with a decreased sensitivity to heparin. There exist also different types of acquired deficiency due to a diminished production, an increased loss or an increased consumption of the inhibitor. Because AT deficiency is the cause of an increased thrombotic tendency in many cases the therapeutic and prophylactic possibilities are described. Since highly purified concentrates became available, substitution was attempted in cases of AT deficiency. It was found to be of greatest importance in cases of disseminated intravascular coagulation (DIC) which is a frequent consequence of septic or traumatic shock. In such cases an adequate AT-substitution can even be lifesaving as could be shown in different trials.
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PMID:Hereditary and acquired antithrombin deficiency. 1044 57

Four-factor PCCs are most frequently used for replacement of vitamin K-dependent clotting factors and inhibitors proteins C and S in patients bleeding after phenprocoumon or warfarin overdose, in vitamin K-deficient patients presenting life-threatening bleeding, and liver disease. Since many of these patients are prone to thromboembolic complications including DIC, all conceivable measures should be taken against the thrombogenic potential of PCC preparations. This thrombogenic potential of PCCs is obviously dependent on several factors including activated clotting factors, lack of inhibitors of blood coagulation, and coagulation factor overload, as well as predisposing factors referred to recipients and drug interactions. The composition of PCC should meet the following criteria: Antithrombin in addition to heparin for the neutralization of FIXa and FXa should be present in the preparations; no overloading with FII and FX; substantially lower FVII than FIX potencies in order to minimize contamination with or generation of FVIIa; and substantial protein C as well as protein S activities. Quality control should include determinations as recommended by the European Pharmacopoeia. Specific assays for quantification of FIXa and FXa are urgently required, and validity of these assays must be proven in surveys. All lots should also be tested for their FVIIa content. Furthermore, the safety of PCCs must be proven by suitable animal models. Whenever possible, patients receiving PCCs should be under low-dose heparin prophylaxis; simultaneous administration of heparin-neutralizing drugs or antifibrinolytic agents must be avoided.
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PMID:Production and composition of prothrombin complex concentrates: correlation between composition and therapeutic efficiency. 1049 3

Measurement of antithrombin (AT) activity in plasma provides important information for the diagnosis of congential antithrombin deficiency and disseminated intravascular coagulation. When measured in the presence of heparin, plasma antithrombin activity includes heparin cofactor II activity as about 20-30% of the total activity. Antithrombin assay methods measuring plasma anti-F.Xa activity or those measured in the presence of 0.22 M NaCl exclude the influence of HC II activity. Dilution of the plasma sample is necessary to measure the heparin cofactor anti-thrombin activity of AT correctly. A laboratory method that precisely reflects plasma heparin cofactor anti-thrombin activity of AT should be established as the standard laboratory method.
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PMID:[Standardization of the laboratory method for antithrombin activity measurement]. 1198 57


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