Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several papers concerning abnormalities of blood coagulation and fibrinolysis during hyperthyroidism, have been published. Increased von Willebrand Factor (vWF) activity and high fibrinogen levels have been reported. However, there is controversy concerning the presence of a hypercoagulable state in hyperthyroidism. We investigated various hemostatic parameters in 41 hyperthyroid patients and compared them to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with control subjects, fibrinogen, factor IX, vWF, AT III and PAI-1 were significantly increased in patients (p<0.05, p<0.0001, p<0.05, p<0.01 and p<0.0001; respectively), whereas factor X and t-PA were decreased (p<0.05). We showed that free T4 (FT3) levels were correlated with factor VIII activity (r=0.35, p<0.05). FT4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. AT III was inversely correlated with factor VII activity (r=-0.48, p<0.01). Protein C and S were correlated with vWF levels (r=0.58, p<0.0001; r=0.55, p<0.0001, respectively). Protein C was inversely correlated with t-PA (r=-0.39, p<0.01). There was a negative correlation between triglycerides, LDL-C and F X (r=-0.45, p<0.05; r=-64, p<0.01, respectively). Mean platelet volume (MPV) was correlated with anti-thyroid peroxidase (TPO) antibodies (in Graves'disease) and F IX activity (r=0.57, p<0.05 and r=0.39, p<0.05; respectively). We found important differences in the coagulatory /fibrinolytic parameters between the hyperthyroid patients and healthy controls. Hyperthyroid patients may experience vascular endothelial dysfunction and decreased fibrinolytic activity in blood. This endothelial activation may represent a situation with a higher thromboembolic potential.
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PMID:Blood coagulation and fibrinolysis in patients with hyperthyroidism. 1203 Jun 6

Haemostatic disorders caused by Lonomia obliqua caterpillars has reached epidemic proportions in southern Brazil. Here we evaluated coagulation and fibrinolysis in 105 patients after accidental contact with Lonomia obliqua caterpillars. Global coagulation tests were prolonged in most cases and patients were divided into 3 groups according to fibrinogen (Fg) level: <or=0.5 g/l (group A); 0.51-1.5 g/l (group B), >1.5 g/l (group C). There was a significant reduction of factors V, XIII, VIII and prekallikrein in group A, with no change in factors X, II and von Willebrand factor. Thrombin-antithrombin and prothrombin F1+2 were elevated in most patients. Antithrombin and protein S were not changed whereas protein C levels were reduced in group A. Plasminogen and alfa2-antiplasmin levels were significantly reduced in group A and D-Dimer levels were extremely high in all groups, showing that fibrinolysis had been activated, possibly secondary to fibrin production. Levels of t-PA were normal and PAI-1 was mildly elevated in group A. The platelet count remained above 150 x 109 platelets/ml in 97% of cases. In summary, our results suggest that Lonomia obliqua envenoming is characterized by a consumption coagulopathy and secondary fibrinolysis.
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PMID:Blood coagulation and fibrinolytic factors in 105 patients with hemorrhagic syndrome caused by accidental contact with Lonomia obliqua caterpillar in Santa Catarina, southern Brazil. 1257 17

Plasma levels of haemostasis factors (HFs) such as fibrinogen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and D-dimer may be markers of arteriosclerosis for the following reasons: There seems to be no difference in levels of HFs between patients with longstanding stable angina and those with an isolated myocardial infarction. HF levels are generally positively associated with subclinical arteriosclerosis as determined by ankle-arm index and carotid ultrasonography in asymptomatic individuals. Levels of most HFs are positively associated with inflammation, which is an essential part of the initiation and progression of the disease. A rough classification is assigned to the associations found in under (2) and (3). Fibrinogen is strongly associated with subclinical arteriosclerosis and with inflammation; Factor VII is not, while an intermediate group is formed by, for instance, von Willebrand Factor (vWF), Factor VIII (F VIII), t-PA, PAI-1, and D-dimer. Also, the associations of HFs with cardiovascular events follow a similar pattern. Fibrinogen is a strong and consistent risk factor in several studies, Factor VII is not, and a similar intermediate group as mentioned under (2) and (3) exists. It suggests that the risk of cardiovascular events in relation to HF levels is explained by their identity as markers of arteriosclerosis. A causal association between HF levels and the disease is not proven. Out of the HF, the markers of coagulation such as thrombin-antithrombin complex and of fibrinolysis such as D-dimer are more likely to act causally. Increased levels indicate that they are markers of arteriosclerosis, but in addition, they may reflect a low-grade, continuous formation and subsequent lysis of fibrin in the disease. As the latter reflects an increased tendency to thrombosis, a causal association of levels of markers of coagulation and fibrinolysis with arteriosclerosis, although not yet proven, seems likely.
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PMID:Levels of haemostatic factors, arteriosclerosis and cardiovascular disease. 1261 75

The influence of hypothyroidism on haemostasis is controversial; both hypocoagulable and hypercoagulable states have been reported. Hypothyroidism has been associated with atherosclerosis; a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. The aim of the present study was to investigate the markers of endogenous coagulation and vascular endothelial cell function and to evaluate the relationship between serum lipid profile, thyroid hormones and haemostatic parameters in hypothyroid patients. We investigated various haemostatic parameters in 20 patients with hypothyroidism and compared them with 20 euthyroid controls. The relationship between serum thyroid hormones and the haemostatic parameters was examined. The plasma levels of fibrinogen, AT III and PAI-1 were significantly increased in hypothyroid patients compared with the control group, whereas factors VIII and X activity was decreased. We showed that free T3 levels correlated with factor IX activity. Free T4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. aPTT correlated inversely with t-PA activity and positively with protein C activity. Anti-Tg correlated inversely with FV. There was a positive correlation between triglycerides and protein C. Protein S correlated inversely with high density lipoprotein cholesterol. We found a hypofibrinolytic state in patients with hypothyroidism. Our results suggest that the risk of developing thrombosis and ultimately myocardial infarction via high PAI-1 levels may be increased in patients with hypothyroidism, a result in line with recent epidemiological data. However, thyroid hormones may play a role at different levels of the complex haemostatic system.
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PMID:Blood coagulation and fibrinolytic activity in hypothyroidism. 1266 86

We investigated the effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E) on blood coagulation abnormalities and dysfunction of vascular endothelial cells in spontaneously diabetic Otsuka Long-Evans Tokushima Fatty rats. The animals were treated with either EPA-E or lard at a daily dose of 0.3 g/kg/day for 52 weeks by gavage, and their coagulation/fibrinolytic parameters, platelet aggregation, and functions of the vascular endothelial cells were examined. EPA-E significantly improved coagulation-related parameters including prothrombin time, activated partial thromboplastin time, fibrinogen level, and activities of factor II, V, VII, VIII, IX, X, XI, and XII, and antithrombin III, and fibrinolysis-related parameters including plasminogen, tissue-type plasminogen activator, alpha(2)-plasmin inhibitor, and plasminogen activator inhibitor. It also suppressed ADP- or collagen-induced platelet aggregation and the cholesterol/phospholipid molar ratio in platelet membranes at a dose of 0.3 g/kg. In addition, it significantly increased the migration activity of vascular endothelial cells, and decreased the binding of vascular endothelial cells to vascular endothelial growth factor. In contrast, lard had no effect on hypercoagulation, hypofibrinolysis, and platelet hyperaggregation but significantly aggravated the dysfunction of vascular endothelial cells. These data demonstrate that EPA-E beneficially altered certain factors known to promote thrombosis and atherosclerosis in this animal model.
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PMID:Long-term administration of highly purified eicosapentaenoic acid ethyl ester improves blood coagulation abnormalities and dysfunction of vascular endothelial cells in Otsuka Long-Evans Tokushima fatty rats. 1461 17

Plasmin is a direct thrombolytic which has been shown to have a strikingly favorable benefit to risk profile in comparison with plasminogen activators, notably tissue plasminogen activator (t-PA). As heparin is known to increase the risk of hemorrhage when co-administered with a plasminogen activator, we asked whether adjunct antithrombotic agents such as aspirin and heparin would affect the safety of plasmin. Three groups of rabbits were administered plasmin at a dose (4 mg kg-1) designed to induce significant decreases in antiplasmin, fibrinogen and factor (F)VIII, to about 25, 40 and 40%, respectively, of baseline values, but not cause prolongation of the ear puncture bleeding time. In a blinded and randomized trial, the results show that an intravenous aspirin bolus plus heparin administered as a bolus followed by a maintenance continuous infusion did not significantly prolong the bleeding time during plasmin infusion. These data indicate that in the rabbit, concomitant use of aspirin plus heparin does not affect the safety of a therapeutic dose of plasmin.
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PMID:Safety of plasmin in the setting of concomitant aspirin and heparin administration in an animal model of bleeding. 1467 99

During the last few years, the availability of endothelial cell cultures isolated from different vascular regions contributed to a significant increase in understanding the complex pro- and antithrombotic mechanisms in our circulatory system. The most important key enzyme is thrombin. Due to its haemostatic properties this serin protease catalyzes fibrin formation, activation of factors V, VIII and XIII as well as irreversible platelet aggregation. These processes may occur even within the circulatory system in case of endothelial stimulation (e. g. by inflammation mediators) for expression of binding sites for factors IX, IXa, X, Xa, von Willebrand protein and PAF. Thus not only catalytically activated coagulatory cascades, but also enhanced cooperation of platelets and granulocytes will occur. Paradoxically, in low intravascular concentration, thrombin, in combination with a healthy endothelial layer, may be the critical factor for the inhibition of thromboses. Respective antithrombogenic properties will mainly affect pre-venous microvascular circulation. In detail, they include thrombin-induced endothelial formation of antiaggregatory autacoids from platelet release products, anticoagulatory activation of protein C and absorption of active coagulation factors at endothelial heparan/ATIII complexes as well as release of profibrinolytic plasminogen activator of endothelial origin. The understanding of these complex regulatory functions enables not only a critical evaluation of actually discussed haemostasiologic risk factors (enhanced platelet reactivity, high concentrations of factor VII, VIII, fibrinogen, PAI, ATIII), but also the development of new pharmacologic strategies for prevention of thrombosis.
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PMID:[Thrombin: antithrombotic properties and pharmacological consequences]. 1531 3

The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis also termed primary, secondary and tertiary hemostasis. From the platelet transcriptome 6000 mRNA species and represent receptors, ion channels, signalling molecules, kinases, phosphatases, and structural, metabolic and regulatory proteins. This abundance of regulatory proteins points towards the importance of signal transduction in platelet function. First platelets adhere to collagen, this induces activation signals such as TXA(2) that induces further Ca(2+) increase. Consecutively, fibrinogen binds to the integrin alpha(IIb)beta(3) resulting in aggregation.This self-amplifying process is controlled by signals, from endothelial cells, to restrict the platelet plug to the site of vessel injury. Secondary hemostasis (coagulation) consists of an extrinsic and intrinsic pathway. Thrombin is generated via Factor Xa resulting from the extrinsic tenase reaction that is turned of by tissue factor pathway inhibitor. While thrombin generation is maintained via positive feedback mechanisms activating factors V, VIII and XI. Excess thrombin is inhibited by antithrombin or by autodownregulation via activation of protein C. Since minor injuries are common, platelets and plasma clotting factors constantly produce clots to stop bleeding. If clots remained after the tissue healing, the vascular bed would become obstructed with clots therefore this is regulated by fibrinolysis, tertiary hemostasis. Tissue-type plasminogen activator synthesised by the endothelium, converts plasminogen to plasmin, the clot lysis enzyme. Plasmin clears the blood vessels by degrading fibrin. Fibrinolysis is controlled by plasminogen activators inhibitor (PAI-1), alpha2-antiplasmin and alpha2-macroglobulin, and thrombin-activatable fibrinolysis inhibitor (TAFI).
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PMID:The hemostatic system. 1537 10

Semen contains enzymes and inhibitors of the haemostatic system as well as the high molecular weight seminal vesicle (HMW-SV) proteins. The former may have roles in seminal clotting and in liquefaction through "fibrinolytic" activity, which may ultimately affect fertility. Although a limited number of studies have addressed the subject, the role of clotting and fibrinolytic factors in semen remains poorly understood. The liquefaction time and the distribution of components vary across split ejaculates. This may have an important bearing on the way clotting/fibrinolytic factors in semen are assessed. Semen contains tissue factor (TF, Thromboplastin, CD142), which originates from the prostate and is associated with prostasomes. The function of TF (and prostasomes) in semen is still a matter for speculation. Recently the presence of minute amounts of factor VII in semen has been demonstrated but its importance is uncertain. Semen also contains a thrombin-like enzyme, prothrombin fragments 1 and 2 (F1+2), D-dimer (DD) and thrombin-antithrombin (TAT) complexes. The presence of several fibrinolytic factors has been demonstrated in semen but few questions about their potential impact on semen quality have been raised. Factors found include tissue plasminogen activator (t-PA), urinary plasminogen activator (u-PA) and plasmin. There are also traces of fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), factor VIII coagulant activity (VIII:c) and fibrin monomers. The co-ordinate expression of both TF and PAI-1 by decidual cells of the endometrium is believed to be important in maintaining haemostasis during endovascular trophoblast invasion. Kallikrein-like serine protease inhibitors including prostate specific antigen (PSA) are known to be present in semen at high concentrations. In semen PSA is also found in a complex form with protein C inhibitor (PCI) with mutually inhibitory consequences. A better understanding of the spectrum of coagulating and liquefaction agents in semen to include classical haemostatic processes and the pathogenesis resulting from any imbalances between or within either system may provide the basis for the development of more selective and efficient agents affecting global fertility. Here we review aspects of male reproductive physiology in the light of recent findings concerning conventional clotting/fibrinolytic systems in human semen with a view to stimulating further research.
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PMID:Seminal clotting and fibrinolytic balance: a possible physiological role in the male reproductive system. 1546 6

To test the sensitivity of the global assay of overall haemostasis potential (OHP) in detecting hypocoagulation, the OHP was assayed in plasma containing exogenous thrombin (0.04 IU/ml), tissue-plasminogen activator (330 ng/ml), Ca and a platelet reagent. Commercial plasmas with factor II, V, VIII, IX, X, XI, XII or VII deficiency were mixed with normal plasma in different proportions to imitate different severities. Samples from patients with haemophilia and factor XII deficiency were also examined. No clot was found in the absence of factor II/factor X, indicating that the tiny dose of thrombin worked solely as a trigger for the intrinsic pathway activation. Changed levels of the investigated coagulants, apart from factor XII, influenced the outcome. OHPs were decreased in patients with haemophilia but were unchanged or even increased in those with factor XII deficiency. This modified OHP method may therefore be useful for estimating the bleeding tendency in haemophilic patients and to find suitable doses and intervals for prophylactic treatment. It may also be of use in investigations of the effect of antifibrinolytic drugs as well as for identifying a thrombotic tendency in patients with factor XII deficiency. For detection of other coagulation factor deficiencies, our investigations with the commercial plasmas suggest that the OHP assay is also valuable, especially when the intrinsic pathway of the coagulation cascade is impaired.
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PMID:Identifying hypocoagulable states with a modified global assay of overall haemostasis potential in plasma. 1626 34


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