Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Atherosclerosis Risk in Communities Study measured hemostatic variables in nearly 16,000 men and women, aged 45 to 64 years, from four US communities. This report, based on the first 12,681 participants, presents distributions of fibrinogen concentration, factor VII activity, factor VIII activity, von Willebrand factor antigen, protein C antigen, antithrombin III activity, and activated partial thromboplastin time. Many of the hemostatic variables differed between blacks and whites, and by sex and age. For example, compared to whites, blacks had higher mean values of fibrinogen, factor VIII, von Willebrand factor, and antithrombin III, and lower mean values of protein C. Some seasonal fluctuations in hemostatic variables were noted; most notably, mean values of factor VII were lowest and protein C were highest in subjects examined in the summer compared to those examined during the other seasons. These results provide population-based reference values on blacks and whites for those interested in the relation of hemostasis to disease.
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PMID:Distributions of hemostatic variables in blacks and whites: population reference values from the Atherosclerosis Risk in Communities (ARIC) Study. 145 14

Previous studies have demonstrated that platelets or aortic endothelial cells provide an appropriate surface that augments the proteolytic inactivation of factor Va by activated protein C (APC). We have examined the ability of three human tumor cell lines (HepG2, CAPAN-2 and J82) to support the inactivation of human factor Va by human APC in the presence and absence of human protein S. APC-mediated factor Va inactivation on these tumor cell lines was assessed by measuring the ability of residual cell-bound factor Va to augment the proteolytic activation of prothrombin by factor Xa. Each of the tumor cell lines studied supported factor Va inactivation by APC in the presence of calcium ions. HepG2 cell monolayers supported this reaction most effectively, with CAPAN-2 and J82 cell monolayers exhibiting moderate and weak effectiveness, respectively. Although not essential for this reaction, protein S moderately enhanced the rate of factor Va inactivation by APC on these tumor cell lines. In addition, pretreatment of each tumor cell line with rabbit antihuman protein S IgG had little, if any, effect on its ability to support factor Va inactivation by APC. Our data suggest that these, and perhaps other, tumor cells can provide an appropriate phospholipid surface for promoting factor Va binding and rapid inactivation by APC.
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PMID:Inactivation of factor Va by activated protein C on selected human tumor cell lines. 146 18

beta 2-glycoprotein I (beta 2-GP I) is a plasma protein with a high affinity for negatively charged surfaces. In vitro this protein shows a variety of anticoagulant properties (inhibition of contact activation and platelet dependent prothrombinase activity). Therefore we studied the possibility that a hereditary beta 2-GP I deficiency is a risk factor for (familial) thrombophilia. Plasma beta 2-GP I levels were measured in healthy volunteers and four different groups of patients with (familial) thrombophilia. In these 5 groups the prevalence of beta 2-GP I deficiency (i.e. beta 2-GP I antigen less than 77%) was found to be very similar (6.8-12.5%) and statistically not significantly different. This observation suggests that beta 2-GP I deficiency in itself is not a risk factor for thrombosis. One thrombophilic patient was found to be homozygous deficient of beta 2-GP I. The transmission of the defect in his family followed autosomal inheritance. One of his brothers was also homozygous deficient and at the age of 35 years still free of thromboembolic complications. The possibility that beta 2-GP I deficiency could be an additional risk factor for the development of thrombophilia in families with protein C deficiency was evaluated in a panel of 70 unrelated patients with clinically dominant protein C deficiency. The prevalence of beta 2-GP I deficiency in this group of patients (12.8%) was very similar to that in other groups of normals and patients. Moreover, there was no difference in the frequency of beta 2-GP I deficiency in symptomatic and asymptomatic protein C deficient patients.
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PMID:Beta 2-glycoprotein I deficiency and the risk of thrombosis. 150 4

Protein C is a natural anticoagulant glycoprotein which prevents intravascular clot formation. Protein C functions as an anticoagulant when converted to an active serine protease (activated protein C). Activated protein C is formed at the site of the endothelial injury in response to blood clotting and helps limit the size of blood clots. We tested the hypothesis that by temporarily blocking the activation of intrinsic protein C, we could reduce subsequent surgical blood loss from a microvascular surgical wound. The formation of activated protein C was blocked systemically by intravenous administration of a monoclonal antibody (HPC4) which binds to circulating protein C and prevents its conversion to activated protein C. Domestic pigs were blindly pretreated with intravenous HPC4 or saline then underwent partial-thickness skin graft harvesting to create a reproducible microvascular wound. Blood loss was measured from each wound and the hemostatic effect of protein C blockade was compared to intravenous saline alone as well as to topical thrombin or thromboplastin. We found that blocking the activation of protein C significantly (P = 0.005) reduces surgical blood loss in this model by 27% compared to saline control animals. Intravenous HPC4 performed equally as well as topical thrombin or tissue thromboplastin. In addition, topical thrombin acted synergistically with HPC4 to reduce blood loss an additional 44% (P = 0.01) as compared to intravenous HPC4 or topical thromboplastin alone. Autopsies performed 1 week after HPC4 treatment showed no evidence of systemic thrombosis resulting from the protein C blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blockade of protein C activation reduces microvascular surgical blood loss. 152 31

Smooth muscle cells (SMCs) in the rat carotid artery leave the quiescent state and proliferate after balloon catheter injury. The precise signals responsible for this SMC mitogenesis need to be elucidated. Although platelet-derived growth factor (PDGF), a potent SMC mitogen, is released from activated platelets, damaged endothelium, and macrophages, it cannot be solely responsible for this proliferation. In search of other SMC growth factors, we have examined several proteins of the coagulation cascade. At nanomolar concentrations, factors X, Xa, and protein S promote cultured rat aortic SMC mitosis. In contrast, factor IX is only weakly mitogenic, whereas factor VII and protein C fail to stimulate SMC division. Protein S, the most mitogenic of these coagulation cascade factors, stimulates DNA synthesis in cultured SMCs with a time course similar to that of PDGF-AA and without the delay observed for transforming growth factor beta. Antistasin and tick anticoagulant peptide, two specific factor Xa inhibitors, inhibit SMC mitogenesis due to Xa and protein S. Coagulation factors that possess mitogenic activity may contribute to intimal SMC proliferation after vascular injury as a result of angioplasty or vascular compromise during atherogenesis.
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PMID:Coagulation factors X, Xa, and protein S as potent mitogens of cultured aortic smooth muscle cells. 153 56

Protein C (PC) and protein S (PS) are components of a potent, natural anticoagulant system. A deficiency of one of these two inhibitors is associated with thrombotic events in young people. A significant reduction in functional PS activity has been observed during normal pregnancy, and recurrent fetal loss may occur in women with lupus anticoagulant (LA) inhibitor. We measured functional PS activity and free PS antigen in 16 non pregnant patients with LA inhibitor and in 17 normal women as controls. A significant difference was observed between patients and controls in functional PS activity (65 +/- 23% vs 87 +/- 15%, p = 0.02) but not in free PS antigen (88 +/- 17% vs 93 +/- 17%). Functional PS activity decreased only in six patients (37%). Removal of IgG from plasma reduced the difference in functional PS activity between patients and controls. Immunologic IgG levels did not correlate with anti-phospholipid antibodies (APA) activities, activated partial thromboplastin time/kaolin clotting time (aPTT/KCT) data or functional PS activity.
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PMID:Functional protein S in women with lupus anticoagulant inhibitor. 153 34

The influence of two different methods of autologous transfusion, preoperative donor plasmapheresis (Abbott Autotrans) and postoperative autotransfusion (intraoperative blood salvage, Dideco Autotrans), on the intravascular hemostatic system was investigated. Forty-two patients undergoing total hip surgery and preoperative donor plasmapheresis were prospectively randomized into three groups. For substitution of blood loss, patients in group 1 (control group, n = 12) received in addition to cristalloids and colloids only homologous blood, group 2 (n = 14) autologous blood, and group 3 (n = 16) additionally intra- and postoperative autologous fresh frozen plasma (FFP). The investigation included blood parameters (hemoglobin, hematocrit, thrombocytes), clotting status (prothrombin time, plasma thromboplastin time, thrombin time, fibrinogen, plasminogen, and antithrombin III), and immunological methods such as fibrinopeptide A (FPA), thrombin-antithrombin III (TAT), and protein C. No significant difference was found with respect to total amount of infusion, intraoperative blood loss, autologous transfusion, and blood parameters. Excellent quality of the autologous FFP was demonstrated by investigation of the specimens before administration. The autologous packed red cells showed high levels of TAT and FPA as an indicator of thrombin generation. Their administration caused a significant increase in TAT and FPA levels in groups 2 and 3 compared to group 1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Measures for reducing the use of homologous blood. Effects on blood coagulation during total endoprosthesis]. 144 16

Hypercoagulable states are disorders of blood coagulation, which include deficiencies of natural anticoagulants, disorders of the fibrinolytic system, presence of antiphospholipid antibody and abnormalities of platelet function. These disorders are well known causes of venous thromboembolic disease and are being recognized in association with arterial thromboembolic occurrences with increasing frequency. The performance of standard prosthetic vascular reconstructions may result in disastrous outcomes in patients with unrecognized and untreated hypercoagulable states. From 1986 to 1990, we identified 12 patients with hypercoagulable states, six of whom presented with evidence of arterial thromboembolism. All of the patients were men who smoked and were somewhat younger than the usual patient with atherosclerosis. Their ages ranged from 41 to 62 years. Four patients presented with ischemic rest pain, one patient with blue toe syndrome and one with rapidly progressive claudication. Four patients had undergone prior vascular reconstruction and two had previous pulmonary emboli. Evaluation of these patients to identify hypercoagulability included determinations of prothrombin time (PT) and partial thromboplastin time (PTT), platelet count, antithrombin III, protein C, free protein S and total protein S levels, along with platelet aggregometry. Two patients had protein S deficiency, one had protein C deficiency, one patient had protein C and S deficiency and two patients had hyperaggregable platelets. Four patients had prosthetic reconstructions and two had autogenous reconstructions. Three of the four patients undergoing prosthetic reconstructions had subsequent loss of limb and one patient died. Only one patient with prosthetic reconstruction had a patent graft on long term anticoagulation. Both patients undergoing autogenous procedures had successful revascularization with limb salvage.
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PMID:Hypercoagulable states in arterial thromboembolism. 154 37

This study examines the assumption that both the anticoagulant and fibrinolytic activity that follow the generation of thrombin induced by infusion of factor Xa/PCPS are due to generation of activated protein C. Untreated controls or animals given unrelated antibody were compared with animals pretreated with a specific monoclonal antibody to protein C (HPC4). Compared with untreated controls excess HPC4 substantially reduced the level of protein C activation as observed by protein C immunoblotting and enzyme-linked immunosorbent assay for antitrypsin/activated protein C complexes. Despite this, the anticoagulant activity as reflected by the decline of factors Va and VIIIa levels (as observed by coagulation assays and by factor V immunoblotting) was significantly greater than controls. The fibrinolytic activity (as observed by assays of tissue plasminogen activator, D-Dimer, alpha 2-antiplasmin) also was significantly greater than controls. We conclude that neutralization of the protein C anticoagulant system while resulting in a significantly more intense coagulant response to Xa/PCPS does not preclude inactivation of factors Va and VIIIa and the full expression of the fibrinolytic response. We conclude further that after thrombin generation in vivo, protein C activation is not a prerequisite for the promotion of the fibrinolytic response previously observed, and that the inactivation of factors Va/VIIIa may be mediated by enzymes other than activated protein C. The reduction in alpha 2-antiplasmin levels in association with increased tissue plasminogen activator activity suggests that plasmin is a likely candidate.
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PMID:Anticoagulant and fibrinolytic activities are promoted, not retarded, in vivo after thrombin generation in the presence of a monoclonal antibody that inhibits activation of protein C. 155 68

An inherited deficiency of protein C, a recognized hypercoagulable state, may cause a clinically significant deep venous thrombosis. Only some persons with a deficiency of protein C experience thrombosis, and almost always the thrombotic event occurs in the venous circulation. Warfarin-induced skin necrosis, a rare event observed in some patients soon after treatment with warfarin is begun, is believed to be another manifestation of this deficiency. We describe a young woman whose basal functional and antigenic levels of protein C were about 45% and who experienced both deep venous thrombosis and warfarin-induced skin necrosis in a clinically severe course. Evidence for lupus anticoagulants was present, with prolonged activated partial thromboplastin time that was corrected when lysed platelets were added, prolonged Russell's viper venom time, anticardiolipin antibodies, and other laboratory evidence. Lupus anticoagulants are associated also with a significant incidence of thrombosis, including arterial thrombosis, and this patient developed concurrently arterial thrombosis. The combined effects of protein C deficiency and lupus anticoagulants, exacerbated by other potentially thrombogenic conditions, are believed responsible for the severe thrombotic events experienced by this patient.
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PMID:Concurrent protein C deficiency and lupus anticoagulants. 156 44


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