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

The mesothelium contains both procoagulant and fibrinolytic activities. An imbalance between these activities could account for the abnormal fibrin turnover and pleural fibrin deposition that is characteristic of pleural inflammation. Procoagulant activity of human pleural mesothelial cells (HPMC) is in part due to tissue factor, and the prothrombinase complex can also assemble at the HPMC surface. HPMC express tissue plasminogen activator (tPA) but no detectable fibrinolytic activity in a fibrin plate assay. Inhibition of HPMC fibrinolytic activity is due, in part, to elaboration of plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) as well as antiplasmins. Synthesis of PAI-1 and PAI-2 is inhibited by actinomycin D and cyclohexamide. HPMC PAI-1 is increased by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), as is tPA release, while PAI-1 mRNA is unchanged and tPA mRNA is increased. PAI-2 release is induced by TNF-alpha and TGF-beta. Because they are a rich source of PAI-1 and PAI-2, HPMC may contribute to the high levels of these inhibitors in pleural exudates. Stimulation of HPMC by TNF-alpha or TGF-beta in vitro did not alter HPMC procoagulant activity nor the balance of elevated PAI and antiplasmins relative to PA, changes that collectively favor formation and persistence of pericellular fibrin.
 ...
PMID:Pathways of fibrin turnover of human pleural mesothelial cells in vitro. 138 10

Six healthy male volunteers were served 4 strictly controlled isoenergetic diets differing in fat (20% or 50% of energy) and fiber contents (2 or 4 g/MJ) for periods of 2 days. The diets were served in random order with at least 5 days separating each diet period. Blood samples for determination of factor VII clotting activity using human (FVIIc) and bovine thromboplastin (FVIIbt), and for assessment of factor VII antigen (FVIIag), tissue-plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, PAI activity, t-PA and euglobulin fibrinolytic activity, and triglyceride and insulin levels were collected regularly on the second day of each diet period. The high-fat diets resulted in significantly increased postprandial FVIIbt levels (peak values: 131% vs. 95%, P < 0.01), and higher postprandial FVIIbt/FVIIag ratios (peak values: 1.42 vs. 1.16, P < 0.01) compared with the low-fat diets. Fibrinolytic variables were not affected by the dietary changes and consistently showed characteristic U-shaped (t-PA and PAI-1 antigen, PAI activity), or inverted U-shaped (t-PA and euglobulin fibrinolytic activity) circadian patterns with troughs and peaks, respectively, at 17:30-21:30 h. The dietary fiber content had no significant influence on any of the measured variables. Our findings indicate that high-fat diets may increase blood thrombogenicity by virtue of augmented postprandial activation of factor VII.
 ...
PMID:Dietary effects on circadian fluctuation in human blood coagulation factor VII and fibrinolysis. 839 16

Throughout the last few decades, different factors have been related to coronary stenosis which is clinically evidenced by coronary heart disease, the leading cause of death in developed countries. Different experimental models have contributed towards defining some of these factors, and to an understanding of the physiopathology of the atherosclerotic lesion. The genetic basis related to individual responses to the same event is currently being established. As endothelial injury reparative mechanisms are fundamental in atherosclerosis pathogeny, patients who experiment restenosis after undergoing revascularization procedures are useful human models in the study of these processes. We review from the literature the genetic factors related to thrombus formation, which may be associated with restenosis after percutaneous transluminal coronary angioplasty, in order to define the most suitable anticoagulant therapy for each patient. We refer to the recently characterized gene for the platelet receptors and its relationship with fibrinogenous, factor Xa, PAI-I, and the involvement of apolipoprotein (a) in the coagulation process.
 ...
PMID:[Blood coagulation, genetics and post-angioplasty restenosis]. 905 43

We examined various hemostatic abnormalities in 395 patients with disseminated intravascular coagulation (DIC), in 177 patients in a Pre-DIC stage, and in 99 patients who did not exhibit DIC. Pre-DIC was defined as the condition at least one week before the onset of DIC. The differences in activated partial thromboplastin time (APTT), FDP, prothrombin time (PT) ratio, fibrinogen, and platelet count between DIC and Non-DIC patients were significant, but there were no significant differences in these parameters between Pre-DIC and Non-DIC patients. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (sFM), prothrombin activated peptide F1 + 2 (F1 + 2), thrombomodulin (TM), tissue type plasminogen activator (t-PA), and PA inhibitor (PAI-I) in DIC patients were significantly higher than levels in Non-DIC patients. However, only TAT, sFM and PAI-I values in the Pre-DIC patients were significantly higher than the values in the Non-DIC patients. Almost all the hemostatic molecular markers examined had high sensitivity for DIC, but only TAT and PPIC had high sensitivity for Pre-DIC. Specificity for DIC was also high with TAT, sFM, and F1 + 2. Early diagnosis and early treatment are important in DIC; we believe that it is possible to predict Pre-DIC by assessing values for the combination of hemostatic molecular markers.
 ...
PMID:Diagnosis of pre-disseminated intravascular coagulation stage with hemostatic molecular markers. The Mie DIC Study Group. 911 56

To investigate whether there are differences in haematology and coagulation indices in arterial and venous plasma, and whether those changes related to damage to the endothelium in atherosclerosis, we obtained blood samples from 22 subjects undergoing diagnostic angiography. There were no differences in any of the 15 routine haematological indices measured. There were no differences in prothrombin time, activated partial thromboplastin time, fibrinogen, tissue plasminogen activator, D-dimer, leucocyte elastase, soluble P-selectin or von Willebrand factor. In venous samples, von Willebrand factor was lower in serum than in plasma (p < 0.0001). Levels of the tissue plasminogen activator/plasminogen activator inhibitor-1 (tPA/PAI-1) complex were markedly higher in arterial blood than in venous blood (p = 0.004) and plasma viscosity was higher in venous blood (p = 0.0014). Consequently, with the exception of viscosity and the tPA/PAI complex, we can find no differences in arterial blood compared to venous blood which can contribute to the debate regarding the mechanism of damage to arterial endothelial cells but the relative protection of venous endothelial cells from injury in atherosclerosis.
 ...
PMID:Haematology and coagulation indices in paired samples of arterial and venous blood from patients with arterial disease. 911 85

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.
 ...
PMID:Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. 957 11

To elucidate potential causes for differing bleeding phenotypes of haemophilic patients of identical degree of coagulation factor deficiency, we investigated 21 male patients with severe haemophilia. Median annual coagulation factor demand and the extent of haemophilic arthropathy were used to discriminate between intensely and less intensely haemorrhagic phenotypes. Haemophiliacs with a median annual coagulation factor demand of 800 IU per kg bodyweight or more and with three or more joints affected by haemophilic arthropathy represented the intensely haemorrhagic phenotype group; all other patients comprised the less intense group. The discriminator values represent the respective medians of the overall group. The results of activated partial thromboplastin time, endogenous thrombin potential, pro- and anticoagulant factor analysis did not differ between the two groups. Median tissue-type plasminogen activator concentration (TPA) was elevated significantly in haemophiliacs with an intensely haemorrhagic phenotype, as was the activity of the thrombin-activatable fibrinolysis inhibitor. Median activity of the plasminogen activator inhibitor 1 (PAI 1) and the concentration of TPA-PAI 1 complexes were increased to approximately double those in nonsevere haemophiliacs. Coexistent congenital thrombophilia was found significantly more often in the less intensely haemorrhagic group. Thus, increased stimulation of the fibrinolytic system was associated with a more intensely haemorrhagic phenotype in our patients. We hypothesize that ineffective haemophilic haemostasis in response to trauma evokes a protracted stimulation of the entire haemostatic system, including costimulation of fibrinolysis. The absence of coexistent congenital thrombophilia predisposes to excess stimulation of fibrinolysis, which cannot be downregulated effectively due to the dysfunctional intrinsic pathway. The association of a more intensely haemorrhagic phenotype with a paradoxical hyperstimulation of the fibrinolytic system resembles a vicious circle, where bleeding seems to cause predisposition to more bleeding.
 ...
PMID:Paradoxical hyperfibrinolysis is associated with a more intensely haemorrhagic phenotype in severe congenital haemophilia. 1241 Jun 45

During normal pregnancy the hemostatic balance changes in the direction of hypercoagulability, thus decreasing bleeding complications in connection with delivery. The most important initial factor for acute hemostasis at delivery is, however, uterine muscle contractions, which interrupt blood flow. Global tests such as Sonoclot signature, the Thromboelastogram, and a new method analyzing overall plasma hemostasis, all show changes representative of hypercoagulability during pregnancy. Increased endogenous thrombin generation, acquired activated protein C resistance, slightly decreased activated partial thromboplastin time (aPTT) and increased prothrombin complex level (PT) measured as international normalized ratio (INR) of less than 0.9 have been reported as well. In normal pregnancy, the platelet count is within normal range except during the third trimester when benign gestational thrombocytopenia, 80 to 150 x 10 9/L, can be observed. Platelet turnover is usually normal. Activation of platelets and release of beta-thromboglobulin and platelet factor 4 are reported. The bleeding time is unchanged during normal pregnancy. Most blood coagulation factors and fibrinogen increase during pregnancy. Factor (F) XI is the only blood coagulation factor that decreases. Blood coagulation inhibitors are mainly unchanged but the level of free protein S decreases markedly and the level of tissue factor pathway inhibitor increases. Thrombomodulin levels increase during pregnancy. Fibrinolytic capacity is diminished during pregnancy, mainly because of markedly increased levels of plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and plasminogen activator inhibitor-2 (PAI-2) from the placenta. Thrombin-activated fibrinolysis inhibitor is reported to be unaffected. The total hemostatic balance has been studied by analyses of prothrombin fragment 1+2, thrombin-antithrombin complex, fibrinopeptide A, soluble fibrin, D-dimer, and plasmin-antiplasmin complex. There is activation of blood coagulation and a simultaneous increase in fibrinolysis without signs of organ dysfunction during normal pregnancy. These changes increase as pregnancy progresses. During delivery, there is consumption of platelets and blood coagulation factors, including fibrinogen. Fibrinolysis improves and increases fast following childbirth and expulsion of the placenta, resulting in increased D-dimer levels. These changes are self-limiting at normal delivery. The hemostatic changes, noted during pregnancy, normalize after delivery within 4 to 6 weeks. Platelet count and free protein S, however, can be abnormal longer. Hemostasis should not be tested earlier than 3 months following delivery and after terminating lactation to rule out influences of pregnancy. PAI-1 and PAI-2 levels decrease fast postpartum, but PAI 2 has been detected up to 8 weeks postpartum. alpha 2 -antiplasmin, urokinase, and kallikrein inhibitor levels have been reported to be increased 6 weeks postpartum.
 ...
PMID:Hemostasis during normal pregnancy and puerperium. 1270 15

To better understand potentially reversible causes of idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, and an apparent association of IIH with polycystic-ovary syndrome (PCOS), we assessed associations of IIH with coagulation disorders and with PCOS in 38 women with well-documented IIH. Fifteen women were found to have PCOS; 14 of them were obese, with a body-mass index (BMI) greater than 30 kg/m(2), and 10 were extremely obese (BMI > or = 40). Factor VIII concentration was high (>150%) in 9 of 38 (24%) IIH cases, compared with 0 of 40 healthy adults controls (P(f) =.0009). Familial aggregation of high concentrations of factor VIII, associated with thrombophilia, was documented in all 5 of the 9 high-level factor VIII probands' families who were sampled. Activated partial thromboplastin time (APTT) was prolonged (> or =31.5 seconds) in 10 of 38 (26%) IIH cases, compared with 1 of 32 (3%) controls (P(f) =.009) and, in 4 of these cases, was accompanied by the lupus anticoagulant. Plasminogen activator inhibitor activity (PAI-Fx) was high (>21.1 U/mL) in 9 of 38 cases (24%), compared with 1 of 40 controls (3%) (P(f) =.006). Lipoprotein A was high (> or =35 mg/dL) in 13 of 37 cases (35%), compared with 5 of 40 controls (13%) (P(f) =.03). IIH cases did not differ (P >.05) from controls for homocysteine, proteins C and S, free S, antithrombin III, ACLAs IgG and IgM, dilute Russell's viper venom time, Factor XI, factor V Leiden G1691A, G20210A prothrombin, C677T MTHFR, plasminogen activator inhibitor 4G/5G, or platelet glycoprotein PL A1A2 mutations. Exogenous estrogens (n = 23), clomiphene (n = 1), or pregnancy (n = 4) accompanied the first appearance of IIH in 28 women. PCOS and coagulation disorders, often augmented by exogenous estrogens or pregnancy, are associated with IIH.
 ...
PMID:Idiopathic intracranial hypertension: associations with coagulation disorders and polycystic-ovary syndrome. 1287 84

A randomized controlled multicenter study was undertaken to monitor the effects on hemostasis of two once-a-month injectable contraceptive preparations, Mesigyna (50 mg norethisterone enanthate and 5 mg estradiol valerate) and Cyclofem (25 mg medroxyprogesterone acetate and 5 mg estradiol cypionate) in comparison with a well-known oral contraceptive (OC) Ortho-Novum 1/35 (norethisterone 1 mg and ethinyl estradiol 35 microg). A total of 378 volunteers from four centers (Bangkok, Hangzhou, Santiago and Singapore) were monitored. Blood sampling took place in one pretreatment cycle, the third and ninth injection intervals and one posttreatment cycle. In each of the three treatment groups, a rise in hemoglobin, and increases in platelet count and in prothrombin time were observed. With treatment there was a significant increase in activated partial thromboplastin time among Mesigyna users, no change among Cyclofem users and a significant decrease among OC users. OC use led to increases in plasma levels of fibrinogen, factor VII, factor X, plasminogen, protein C and decreases in plasma levels of t-PAI and antithrombin. Use of combined injectables induced no change (Cyclofem) or decreases (Mesigyna) in plasma levels of fibrinogen, factor VII, factor X and antithrombin. Use of both combined injectables led to decreases in protein C, slight decreases in plasminogen and increases in plasminogen and fibrinogen. Overall, the injectable preparations may be more beneficial than the oral preparation in not enhancing a hypercoagulable state because of the reduced synthesis of fibrinogen, factors VII and X; however, decreases in antithrombin and protein C, which are potent coagulation inhibitors, may raise some concern. Whether these changes can lead to modifications in the risk of arterial or venous disease can only be ascertained by conducting epidemiological studies.
 ...
PMID:Comparative study of the effects of two once-a-month injectable contraceptives (Cyclofem and Mesigyna) and one oral contraceptive (Ortho-Novum 1/35) on coagulation and fibrinolysis. 1456 36


1 2 Next >>