Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, tissue-Plasminogen Activator were functionally evaluated. Antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes and fibrinolytic specific product B beta 15-42 were also determined. Compared to the control group diabetic patients displayed significantly higher levels of Fibrinogen (p < 0.01), Factor VII (p < 0.01), Thrombin-Antithrombin complexes (p < 0.01) and Plasminogen Activator Inhibitor-1 activity (p < 0.01). Regardless of the normal level of the tissue-Plasminogen Activator-related antigen, diabetic patients had tissue-Plasminogen Activator activity lower than the control group (p < 0.05). Coagulation Factor VII and Thrombin-Antithrombin complexes were increased only in the patients with poor metabolic control (p < 0.01). Activated Partial Thromboplastin Time, Prothrombin Time, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, B beta 15-42 fibrin peptide were found to be in the normal range. Fibrinogen correlated positively with fasting blood glucose (p < 0.05) and Thrombin-Antithrombin complexes with glycosylated haemoglobin (p < 0.05), whereas Factor VII was positively correlated with glycemia (p < 0.01) and glycosylated haemoglobin (p < 0.05). Higher levels of Fibrinogen were found in patients affected by nephropathy (p < 0.005) or neuropathy (p < 0.05). These results demonstrate an impairment of the haemostatic balance in diabetic patients, that is a possible hypercoagulable state, which represents an important factor in the pathogenesis of atherosclerotic complications.
 ...
PMID:Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus. 144 May 30

Antibody inhibitors against human thrombin are rare and have remained poorly characterized. We report the case of a 40-yr-old patient who developed a potent thrombin inhibitor revealed by mild bleeding symptoms and marked prolongation of most laboratory clotting times. After two years of evolution, he died from cerebral hemorrhage. The inhibitor, a polyclonal IgG, was associated with hematological and immunological criteria of autoimmune disorder. Antithrombin IgG was isolated from the patient's plasma by protein A- and thrombin-affinity chromatography. Fab fragments inhibited amidolytic activity of alpha thrombin, and thrombin-thrombomodulin catalyzed protein C activation with a Ki of approximately 10(-8) M in a noncompetitive manner. Alpha to gamma conversion of thrombin resulted in a moderate loss of affinity for the inhibitor. Upon complex formation of thrombin with staphylocoagulase or alpha 2-macroglobulin (alpha 2M), inhibition was decreased by two orders of magnitude and acquired an apparent competitive character. In Western blot experiments, the antibody reacted with active alpha-thrombin, did not react with chloromethylketone-inhibited thrombin and reacted with a lower affinity with iPr2P-thrombin. The inhibitor did not block thrombin binding to benzamidine-, heparin-, or fibrin-Sepharose, but displaced proflavin from its complex with thrombin. Taken together, these results indicate that the patient's autoantibody recognized a conformational structure which includes, at least in part, the apolar binding site adjacent to the catalytic site of thrombin.
 ...
PMID:An acquired antithrombin autoantibody directed toward the catalytic center of the enzyme. 171 42

Extrinsic coagulation pathway inhibitor may be an important regulator of haemostasis to prevent thrombosis after tissue damage. The functional activity of this inhibitor was determined using a chromogenic substrate assay, and compared to the activities of antithrombin, heparin cofactor II and protein C during the perioperative period of elective hip replacement (n = 28), cholecystectomy (n = 11), and vascular surgery (n = 5). Peroperatively, all the inhibitors decreased rather similarly and to the same degree as the decrease in albumin concentration. The decreases during hip surgery were about 2-fold the decreases observed during cholecystectomy. A significant peroperative increase in extrinsic pathway inhibitor activity was observed in vascular surgery, probably due to a bolus injection of heparin. Antithrombin, heparin cofactor II and protein C levels normalized on days 3-5 postoperatively in all three patient groups. Sustained low levels of extrinsic pathway inhibitor were observed on postoperative days 1 to 7 in hip surgery patients. Apparently, extrinsic pathway inhibitor is not an acute phase reactant. In uncomplicated surgery, the decreases of the coagulation inhibitor levels are mainly due to hemodilution.
 ...
PMID:Extrinsic pathway inhibitor in elective surgery: a comparison with other coagulation inhibitors. 259 60

Serial determinations of plasma coagulation inhibitor levels were performed with chromogenic substrate activity assays in 7 patients with cancer. At time of diagnosis normal median activities of Antithrombin, Protein C, Heparin Cofactor II and Extrinsic Pathway Inhibitor were found. The inhibitor activities changed significantly with the progress of malignant disease; Antithrombin, Protein C and Heparin Cofactor II decreased whereas Extrinsic Pathway Inhibitor increased. Determinations in 13 additional patients in the terminal phase of cancer confirmed this finding. The inhibitor activities were expressed in per cent of a pooled reference plasma. In the total series of 20 patients studied, median activity of Extrinsic Pathway Inhibitor was 183% (range 61-378%) and significantly (p less than 0.005) above age-adjusted normal reference 10 days (range 1-20 days) prior to death. Median activities of Antithrombin was 59% (range 20-109%), of Protein C 54% (range 24-130%) and Heparin Cofactor II 59% (range 33-110%), all significantly below age adjusted normal reference (p less than 0.001). The coagulation inhibitor levels seem related to the stage of disease in patients with cancer.
 ...
PMID:High plasma levels of extrinsic pathway inhibitor and low levels of other coagulation inhibitors in advanced cancer. 259 46

Protein C inhibitor (PCI), antithrombin, and heparin cofactor II are members of the serine proteinase inhibitor (serpin) superfamily that inhibit proteinases at rates which increase in the presence of the glycosaminoglycan heparin. These studies were undertaken to understand how PCI activity is modulated by various substances that are found in or interact with the vascular endothelium/basement membrane. The effects of antithrombin-heparin, thrombomodulin, vitronectin and leukocyte elastase on PCI-thrombin and PCI-activated protein C (APC) interactions were investigated. Antithrombin, which does not inhibit APC but which does bind to heparin/heparan sulphate with higher affinity than PCI, caused only a small decrease in the inhibition rate of PCI-APC in the presence of unfractionated heparin. Thrombomodulin, a chondroitin sulphate-containing proteoglycan, accelerated PCI inhibition of thrombin and APC. PCI-thrombin in the presence or absence of heparin bound plastic absorbed vitronectin, but neither PCI alone nor PCI-APC bound. Vitronectin also decreased the inhibition rate of PCI-thrombin and PCI-APC in the presence of low concentrations of heparin. Leukocyte elastase proteolytically inactivated PCI in a reaction that was accelerated by heparin. Overall, these results indicate that PCI activity is modulated by these endothelial cell/basement membrane-based substances in similar ways as other heparin-binding serpins, especially antithrombin.
 ...
PMID:Modulation of protein C inhibitor activity. 753 47

Previous studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2.132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinogenemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfibrinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% CI 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% CI 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% CI 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78, 95% CI 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.
 ...
PMID:Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism--results of the Spanish Multicentric Study on Thrombophilia (EMET-Study). 906 91

Danazol, a synthetic attenuated anabolic steroid, has been administered for 36 months to a 32 year old male with hereditary Protein S (PS) deficiency who had become non-compliant for warfarin therapy. The patient has an eleven year history of venous thrombosis. Since danazol therapy was initiated, the patient has not experienced a thrombotic event or adverse side-effects. Levels of PS, other inhibitors, fibrinolytic components, and markers for thrombin and platelet activation were measured prior and subsequent to therapy. Following danazol administration, marked and sustained increases were noted in Free Protein S, Antithrombin, and Protein C. Platelet CD62 (P-selectin) positivity which was elevated before therapy, decreased to assay threshold limits within five weeks. Both Prothrombin Fragment 1.2 and thrombin-antithrombin complexes were elevated post danazol therapy indicating continued clearance of generated thrombin. These data suggest that the protective effect provided by danazol in this patient with hereditary PS deficiency, may in large part be due to suppression of platelet activation by thrombin inhibition than simply through elevation of PS.
 ...
PMID:Efficacy of danazol in a patient with congenital protein-S deficiency: paradoxical evidence for decreased platelet activation with increased thrombin generation. 930 21

The majority of fatal acute myocardial infarctions occur in the elderly. Since these events are predominantly thrombotic, we studied the cross-sectional associations of the anticoagulant proteins Antithrombin, Protein C, Protein S. and Tissue Factor Pathway Inhibitor (TFPI) in a subgroup (n = 400) of the Cardiovascular Health Study (a study of healthy men and women > or = 65 years) free of clinical cardiovascular disease (CVD). We did not observe any strong age-associated trends, although Protein C was lower in older women (p < or = 0.001), and TFPI was higher in older men (p < or = 0.01). The inhibitors were highly intercorrelated, and were associated with increased levels of inflammation-sensitive proteins (e.g., fibrinogen. plasminogen), lipids (especially total and LDL-cholesterol), and coagulation factors, such as Factors VIIc, IXc, and Xc. None was associated with the procoagulant markers Prothrombin Fragment F1-2 or Fibrinopeptide A. Only TFPI was associated with subclinical atherosclerosis: ankle-arm index and internal carotid artery stenosis, p trend < or = 0.01; and carotid wall thickness, p trend < or = 0.05. In multivariate analysis the independent predictors of TFPI were levels of fibrinogen; the fibrinolytic marker plasmin-antiplasmin complex; LDL-cholesterol; and carotid wall thickness (R2 for the model = 0.35). In summary, the inhibitors did not appear to increase with age, and were predominantly associated with inflammation markers and lipids. Since markers of thrombin production do increase with age, we hypothesize that an age-related hemostatic imbalance may ensue, with associated increased thrombotic risk. Only TFPI was associated with subclinical CVD, suggesting that it may more closely reflect endothelial damage.
 ...
PMID:Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort. 968 99

Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis, related to the lupus anticoagulant or anticardiolipin antibodies (ACL). Antithrombin (AT), protein C (PC) and protein S are natural anticoagulants with a very important role in the regulation of coagulation and fibrinolysis, and in the prevention of thrombosis. Total protein S (TPS), free protein S (FPS), AT and PC were measured in 53 unselected patients with SLE in order to verify their relation with previous history of thrombosis or the presence of anticardiolipin antibodies (ACL). The influence of prednisone use on the concentration of these natural anticoagulants was also analysed. The control group was formed by 20 blood donors. The PC concentration was increased in patients with ACL, when compared to controls (p < 0.01), or patients without ACL (p = 0.01). FPS levels were decreased in patients with SLE in relation to controls (p = 0.01), but not related to thrombosis or ACL. There was no difference in plasmatic concentration of AT and TPS, between patients and controls. PC, AT and TPS were increased in patients under prednisone use (p < 0.01). There was no association between concentration of natural anticoagulants and a history of thrombosis. Although decreased FPS was found, or results suggest that it seems not to be a risk factor for thrombosis in SLE. Since PC and AT were not decreased, they should not be involved with thromboembolic complications in these patients. The use of prednisone can influence concentration of natural anticoagulants in patients with SLE.
 ...
PMID:Antithrombin, protein S and protein C and antiphospholipid antibodies in systemic lupus erythematosus. 986 23

Vascular occlusion has a central role in the pathophysiology of sickle cell disease (SCD) and, although there is little evidence that thrombosis alone is responsible, patients with sickle cell disease are known to have an ill-defined but increased thrombotic risk. The most serious complication of this in childhood is stroke which occurs in 7-10% of children and a further 14% have asymptomatic cerebrovascular disease (CVD) on imaging. We have performed a comprehensive profile of coagulation inhibitors and markers of thrombin generation in 96 children (83 nontransfused [NTx] and 13 transfused [Tx]) with steady-state SCD and 18 healthy sibling controls. The levels of protein S (free and total) and heparin cofactor II were reduced in both the NTx and Tx groups compared to controls and protein C and APC resistance ratios were reduced in the NTx group only. Antithrombin levels were not different from controls. Thrombin-antithrombin complexes and prothrombin fragment F1+2 were increased in both patient groups. In the NTx subgroups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD. We conclude that children with SCD have a reduction in levels of the majority of the coagulation inhibitors and increased thrombin generation in the steady-state and these are only partially reversed by transfusion. However, these abnormalities do not appear to play a primary role in the development of cerebrovascular disease.
 ...
PMID:Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion. 988 16


1 2 3 4 5 6 Next >>