Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein C inhibitor (PCI) concentration and other parameters of the protein C pathway were studied in 19 patients with symptomatic acute deep vein thrombosis before and during the first 5 days of heparin treatment. The mean levels of PCI antigen and activity decreased rapidly and significantly during the first day of heparin therapy from 83 and 84% to 60 and 59% of the pooled normal human plasma (p less than 0.01), respectively, and to 56 and 54% after 5 days of treatment (p less than 0.01). In contrast, antithrombin III decreased progressively 25% during 5 days of heparin treatment. Protein C antigen and activity and total protein S remained unchanged during heparin treatment. Free protein S was decreased before heparin treatment (83%, p less than 0.05) and increased to normal values after 5 days of treatment. C4b-binding protein was significantly increased before and during heparin treatment (p less than 0.01). Activated protein C (APC) complexed to its two major plasma inhibitors, PCI and alpha 1-antitrypsin (alpha 1AT) were measured by specific ELISA's. Before treatment, 18 of the 19 patients studied had increased levels of APC:alpha 1AT complexes with a mean value of 27 +/- 22 ng/ml (range, 6-86 ng/ml) compared to normal values (8 +/- 2 ng/ml) and 12 of the patients also had detectable APC:PCI complex levels with a mean value of 11 +/- 17 ng/ml (range, 5-68 ng/ml). Both APC:inhibitor complexes decreased significantly during heparin treatment.
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PMID:Protein C inhibitor and other components of the protein C pathway in patients with acute deep vein thrombosis during heparin treatment. 216 56

We developed an ELISA to quantitate complexes of activated protein C (APC) with a major plasma APC inhibitor, alpha 1-antitrypsin (alpha 1AT) in human plasma based on the sandwich principle using two different antibodies directed towards protein C and alpha 1AT, respectively. This ELISA test was specific for APC:alpha 1AT complexes and sensitive to greater than or equal to 150 pg complex. Fifty-one of 56 healthy donors had APC:alpha 1AT complex levels above the detection limit (3 ng/ml) ranging from 4 to 14 ng/ml (mean value +/- SD: 7.6 +/- 2.5 ng/ml). Patients (n = 10) with disseminated intravascular coagulation (DIC) had detectable levels of APC:alpha 1AT complex ranging from 21 to 125 ng/ml (median: 69 ng/ml). Complexes of APC with plasma protein C inhibitor (PCI) were also measured using an ELISA sandwich assay. None of the 30 healthy donors had detectable levels (greater than or equal to 5 ng/ml) of APC:PCI complex, and plasma samples from 9 of 10 DIC patients had detectable concentrations of APC:PCI complex ranging from 10 to 63 ng/ml (median: 22 ng/ml). APC:alpha 1AT complex was detected in 25 of 26 patients with deep venous thrombosis (DVT), with levels ranging from 5 to 136 ng/ml (median: 23 ng/ml), whereas APC:PCI was detected in only 6 DVT patients, with levels between 11 and 105 ng/ml. PCI antigen levels in 70 normals ranged from 56 to 175% (mean +/- SD: 99.1% +/- 24.2%). PCI antigen levels were decreased in DIC patients, in patients with cerebral arterial thrombosis, and in DVT patients undergoing heparin therapy, but not in patients with myocardial infarction. PCI antigen levels were decreased much further in DVT patients receiving heparin compared to those not receiving heparin, showing that heparin therapy is associated with a decrease in PCI levels. The detection in normal subjects and in thrombotic patients of circulating APC:inhibitor complexes supports the view that the protein C pathway is activated during DIC and DVT. Moreover, it emphasizes that both PCI and alpha 1AT are physiologic inhibitors of APC. Thus, measurement of APC complexes may provide sensitive parameters for specific detection of activation of the clotting and protein C pathways.
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PMID:Determination of plasma protein C inhibitor and of two activated protein C-inhibitor complexes in normals and in patients with intravascular coagulation and thrombotic disease. 217 67

Several parameters of fibrinolytic and protein C pathways were evaluated in three groups of patients with high (HR), moderate (MR) and low (LR) postoperative thrombotic risk undergoing major gynaecological surgery. The HR and MR groups were subjected to low molecular weight heparin (LMW) prophylaxis. A significant increase in plasminogen activator inhibitor type 1 (PAI-1) antigen and activity levels was observed in the HR patient group in comparison with the MR and LR groups in the preoperative and early postoperative period. In all the groups studied, the maximum increase in the levels of PAI-1 was seen on day 1 after surgery. However, the D-dimeric levels reached the highest level on day 7. A significant increase in activated protein C:alpha 1 antitrypsin (APC:alpha 1AT) complex levels was observed in the HR group in comparison with the LR group, and a strong decrease in protein C inhibitor in the early postoperative period was detected in all the groups. In spite of heparin prophylaxis, 2 HR patients were diagnosed as deep vein thrombosis (DVT) during the postoperative period. Both patients showed pre-operative levels of PAI-1 antigen or activity and APC:alpha 1AT complexes above the mean + 1 SD of the pre-operative levels in the HR group. In conclusion, in HR patients a hypofibrinolytic and hypercoagulable state was detected in the pre-operative and early postoperative periods. The prophylactic LMW heparin dose used in the present report (20 mg/day x 7) was insufficient to prevent DVT in the HR group. At present our HR patients are given higher doses of LMW heparin (40 mg/day x 7).
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PMID:Alterations in fibrinolytic and protein C pathways in gynaecological surgery: low molecular weight heparin prophylaxis. 798 53

We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels in both PE and DVT patients were significantly increased compared with normal volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were significantly higher than those in DVT patients without PE. These findings indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most sensitive indicators for PE. In these patients, increases in TAT and APC-PCI complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.
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PMID:Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis. 856 33

We examined hemostatic molecular markers in various thrombotic disorders. The efficacy of treatment in relation to the disseminated intravascular coagulation (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 treatment is important. The sensitivity in some of molecular markers was high for both DIC and Pre-DIC. Receiver operating characteristic analysis suggest that soluble fibrin monomer level could be the most useful marker for the diagnosis of DIC. In examination of these markers in deep vein thrombosis, pulmonary embolism, acute myocardial infarction, and cerebral infarction, plasminogen activator inhibitor-1 and activated protein C-protein C inhibitor complex were useful marker for the diagnosis. Increased plasma GMP-140 was suggested to be the activation of platelets. The patients with high levels of plasma thrombomodulin (TM) considered to be a marker of vascular endothelial injuries became poor outcome. We will term these patients with high TM as systemic vascular endothelium injuries syndrome, and treat those by protecting the vascular endothelium.
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PMID:[Study of hemostatic molecular marker]. 913 93

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

Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were significantly increased in patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT) complex were significantly increased in patients with DIC and in those with TTP. Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC, or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC-PCI complex were significantly increased but not those of APC-alpha(1)-AT complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)-AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those undergoing HD. The receiving operating characteristic (ROC) analysis showed that SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60% with DVT and HD. Since the APC-PCI complex was elevated not only in patients with venous thrombosis but also in those with arterial thrombosis, components of the protein C pathway might be useful markers for the diagnosis of arterial thrombosis.
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PMID:Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states. 1093 61

Activated protein C (APC) is a serine proteinase that regulates blood coagulation. In plasma it is inhibited mainly by the protein C inhibitor (PCI). The plasma concentrations of APC-PCI complex is increased in hypercoagulative states such as deep venous thrombosis. Formation of the APC-PCI complex induces a drastic conformational change in PCI that exposes new epitopes (neoepitopes) on the molecule. We have devised a simple immunofluorometric sandwich assay for measurements of the concentrations of APC-PCI complex, employing as the catcher, a monoclonal antibody that has a high affinity (K(D) = 4 x 10(-11) M) for a complexation-specific neoepitope that is expressed on PCI. A monoclonal antibody against protein C is employed as the tracer. The method gives a linear dose-response curve (0.06-50 microg/l), has a low detection limit (0.06 microg/l) and no crossreactivity with native PCI at physiologic plasma concentrations. We have now determined the concentration of the APC-PCI complex in healthy individuals.
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PMID:A sensitive immunochemical assay for measuring the concentration of the activated protein C-protein C inhibitor complex in plasma: use of a catcher antibody specific for the complexed/cleaved form of the inhibitor. 1152 10

A first clinical evaluation has been made of the performance of a newly devised immunofluorometric assay for measuring plasma concentrations of activated protein C (APC) in complex with protein C inhibitor (PCI). The method was compared with testing for other markers of hypercoagulability in a case-control study comprising 123 patients with clinical suspicion of deep vein thrombosis (DVT). The diagnosis was confirmed by ascending phlebography, and the thrombotic burden estimated with a newly developed scoring system. Receiver operating characteristics (ROC) curves calculated to demonstrate the discriminatory capacity of the methods, showed the area under the curves (AUCs) to be similar for the APC-PCI and D-dimer methods. However, in contrast to the D-dimer method, the APC-PCI method measures a well-defined analyte, a prerequisite for reliable comparisons of future clinical studies. The APC-PCI method appears to be particularly useful as a marker for detection of recently developed proximal thrombi.
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PMID:Complexes between activated protein C and protein C inhibitor measured with a new method: comparison of performance with other markers of hypercoagulability in the diagnosis of deep vein thrombosis. 1177 6

Management of venous thromboembolism disease could be improved by new drugs with lower risk of bleeding and without the need of regular monitoring of anticoagulant effect. In this way, idraparinux, anti-Xa inhibitor, has been compared to conventional therapy (coumarins) for the treatment of deep vein thrombosis and pulmonary embolism. Is it worth to treat patients more than six months? This has been evaluated in an interesting study. Prophylaxis after hip replacement surgery is indicated to reduce the risk of venous thromboembolism, new drugs are under investigation. Dabigatran etexilate, a direct thrombin inhibitor, has been shown as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery. In 2007, new european guidelines for non-STsegment elevation acute coronary syndromes have been published. Two new antithrombotic drugs, bivalirudin and fondaparinux, are now part of the different possible choices according to specific considerations. New factor Xa and factor IIa inhibitors are under investigation and are compared to heparin in PCI for NSTE-ACS. Fondaparinux and more recently otamixaban have given interesting results. These new recommendations have not yet taken into account new data published in 2007. What will be the positioning of prasugrel, a new thienopyridine, after the results of theTRITON trial? In patients with SCA treated by PCI, prasugrel reduced the ischemic events, while increasing major bleedings. In 2007, numerous publications and meta-analyses on drug-eluting stents (DES) have been published and tempered the fear about a possible increase in mortality with the use of DES.
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PMID:[What's new on antithrombotics?]. 1895 Jul 43


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