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)

The aim of this study was to investigate the hemostatic system in menopausal women before and after three months of treatment with transdermal estradiol (TTS 50, 50 micrograms/die, n = 13) or coniugated equine estrogen (CEE, 0.625 mg/die, n = 9) by evaluating : beta-thromboglobulin, platelet factor 4, factor VIIag, factor VIIc, fibrinopeptide A-FPA-, thrombin-antithrombin-TAT-complexes, antithrombin-AT-activity, protein C, plasma fibrinolytic activity (euglobulin clot lysis time), plasminogen and antiplasmin activity. FPA levels significantly increased during TTS 50 treatment (p < 0.001) while protein C showed a slight but significant decrease in both treatments (TTS 50 p < 0.001, CEE p < 0.05). TAT complexes and AT were found unaltered. Platelet function and fibrinolytic activity did not significantly change. A significant relationship between FPA and estradiol levels, which were significantly increased during. TTS 50 therapy, was found (r = 0.40, p < 0.05). These findings indicate that unopposed estradiol given by transdermal route induces a slight but significant blood clotting activation, which seems strictly related to its biological activity.
 ...
PMID:Effects of estrogen replacement therapy on thrombin generation. 905 93

Malignancy is a risk factor for thromboembolism and anti-cancer chemotherapy can increase this risk. Prophylaxis of thrombosis with very-low-dose warfarin given concurrently with chemotherapy has a significantly reduced rate of thromboembolism in a randomized trial in women with stage IV breast cancer. In a group of 32 patients randomized in one center (16 subjects on warfarin and 16 on placebo), we have prospectively studied the plasma levels of: 1. Markers of 'in vivo' clotting activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2] and D-dimer), 2. Factor VII (FVII), and 3. Natural anticoagulants (protein C [PC] and antithrombin [AT]). The aims of this study were: 1. to examine whether laboratory tests predicted those patients who developed thrombosis, and 2. to evaluate the effect of very-low-dose warfarin on hemostatic variables. The patients' hemostatic parameters were evaluated before entry into the study and after starting chemotherapy +/- prophylaxis, before each course for nine courses. Before-treatment results were compared to those of a sex and age-matched non-cancer control group. There was a significant elevation of plasma levels of TAT (p <0.001), F1+2 (p <0.001), D-dimer (p <0.0001) and FVIIa (p <0.05), as well as an increase of FVII proteolysis (p <0.05), whereas plasma PC and AT concentrations were not different from controls. After starting chemotherapy, markers of clotting activation were progressively lower in the group receiving warfarin prophylaxis compared to the group on placebo. Differences between the groups became statistically significant (p <0.01) after the 4th course of chemotherapy. Deep vein thrombosis occurred in two patients in the placebo arm. The results of this study indicate that before therapy, an hypercoagulable state is present in stage IV breast cancer, and after starting chemotherapy, abnormalities of hypercoagulation markers persist, however they are reduced by very-low-dose-warfarin. None of the laboratory variables could predict thrombosis in the single patient.
 ...
PMID:The effect of very-low-dose warfarin on markers of hypercoagulation in metastatic breast cancer: results from a randomized trial. 945 16

Blood coagulation tests are useful to diagnose some thrombotic diseases. Particularly, these tests are valuable for the diagnosis of familiar thrombophilia, antiphospholipid antibody syndrome (APS) and disseminated intravascular coagulation (DIC). For the diagnosis of thrombophilia, determinations of both biological activity and antigen level of antithrombin III, protein C and protein S are important for initial screening. Since activated protein C (APC) resistance is extremely rare in Japanese, APC resistant test that based on APTT, is unnecessary to include as one of the screening tests. Detection of activity and antigen level of either plasminogen or fibrinogen is recommended to screen the plasminogen deficiency or dysfibrinogenemia. Determination of lupus anticoagulant is needed for the diagnosis of APS. At this time, the dilute phospholipid APTT (dAPTT) or the dilute Russell viper venom time (dRVVT) may be useful as a screening test for LA because procedure of these tests are basically simple to perform in Japanese laboratory. In the next step, cross mixing test of dAPTT (or APTT) should be perform to make a diagnose of LA more solid. Final confirm tests can be conveniently carried out with kit of either STACLOT or LA-CONFIRM. Platelet count and FDP (or FDP D dimer) assay are two essential tests for the diagnosis of DIC. Criteria of diagnosis for DIC recommended by Blood Coagulation Research Group of Japanese Ministry of Health and Welfare is not unnecessarily appropriate for practical use. TAT and PIC can be a good laboratory tests for early detection of hypercoagulable state in patients with DIC.
 ...
PMID:[Clinical diagnosis of thrombosis and blood coagulation tests]. 956 63

Severely burned patients often present a hypercoagulability situation. However, its magnitude, time course, and relationship with organ failure and outcome remains to be established. Forty-three patients were studied on the first and seventh day after burn for hypercoagulability and fibrinolysis parameters. A hypercoagulability and hyperfibrinolysis state was found the first day after burn demonstrated by high levels of activated factor VII (VIIa, p<0.01), thrombin-antithrombin III complex (TAT, p<0.01), tissue plasminogen activator (t-PA, p<0.001) and D dimer (DD, p<0.01) and low levels of antithrombin III (ATIII, p<0.01), protein C (PC, p<0.01), plasminogen (PG, p<0.001) and alpha2 antiplasmin (AP, p<0.001). A paradoxical coexisting hypofibrinolysis was found as suggested by a low global fibrinolytic activity in the euglobulin plasma fraction fibrin plate assay (FA, p<0.01) and high levels of tissue plasminogen activator inhibitor type 1 (PAI-1, p<0.01). On day 7, a less marked hypercoagulability situation was found, with low ATIII (p<0.01) and PC (p<0.01), persisting the hypofibrinolytic situation observed on the first day. Non-survivors (NS) showed higher levels of VIIa (p<0.01), TAT (p<0.05) and t-PA (p<0.05), and lower levels of ATIII (p<0.05), PC (p<0.05) and AP (p<0.001) than survivors (S) on the first day. Also, there was a positive correlation of Marshall organ failure score with ATIII, (r2=0.49, p<0.001), PC, (r2=0.14, p<0.045) and PG levels, (r2=0.41, p<0.0003). Severely burned patients show a state of transient disseminated intravascular coagulation, related to the development of organ failure and outcome.
 ...
PMID:Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma. 963 Mar 8

A combined hemostatic defect consisting of a reduction in certain procoagulants, anticoagulants (antithrombin III-ATIII-, protein C-PC-) and components of the fibrinolytic system (plasminogen-Plg-) was demonstrated in very-low-birth-weight infants (VLBW <1,500 g) with gestational age 26-32 weeks. Sixteen of them were healthy, 28 were suffering from RDS and 24 from septicemia. The hemostatic defect was more profound in the RDS group, nevertheless increased TAT (thrombin + ATIII complex) and/or PAP values (plasmin + a2-antiplasmin complex) was a more frequent finding in the septicemic group of infants (91.8 vs. 17.9%). Moderate-to-severe thrombocytopenia was detected in a higher percentage in the septicemic (70.8%) than in the RDS group (50%), and increased D-dimers were demonstrated in 34.8 and 28.6% of the infants, respectively. Elevated TAT or PAP values were not always associated with gross coagulation abnormalities, and advanced disseminated intravascular coagulation (DIC) was only documented in 16.7% of the septicemic and 7.1% of the RDS infants. None of the VLBW neonates presented with clinical evidence of thrombosis, although hemorrhagic manifestations were apparent in 34.8 and 14.3% of the neonates with septicemia or RDS, respectively, mainly due to DIC or severe thrombocytopenia. In conclusion, increased TAT and/or PAP values are good indicators of the in vivo activation of the hemostatic system, but still their impact on sick neonates morbidity and mortality remains unknown.
 ...
PMID:Indications of coagulation and/or fibrinolytic system activation in healthy and sick very-low-birth-weight neonates. 974 62

Hemostatic abnormalities were examined in 55 patients during maintenance hemodialysis (HD). Before HD, plasma protein C and protein S antigens were almost within the normal range, while plasma thrombin-antithrombin III complex (TAT III) and plasmin-plasmin inhibitor complex (PPIC) levels in HD patients were increased slightly, and plasminogen activator inhibitor 1 level was significantly increased, compared to that in normal volunteers. Plasma activated protein C (APC) and protein C inhibitor (PCI) complex and APC alpha 1 antitrypsin (alpha 1AT) complex were not detected in normal volunteers; however, plasma APC-PCI complex was increased in 36 of the patients and plasma APC-alpha 1AT complex was increased in 25 patients. Plasma PCI levels in these patients before HD were significantly decreased. Plasma TAT, PPIC, and tissue type plasminogen activator levels were significantly higher before HD than after 1 hour HD and at the end of HD, while the changes in plasma protein C antigen, protein S antigen, PCI antigen, APC-PCI complex, and APC-alpha 1AT complex were not significant after 1 hour of HD or at the end of HD compared to levels before HD. Plasma PCI levels were correlated with APC-PCI complex, suggesting that decreased PCI levels might be caused by the activation of protein C.
 ...
PMID:Increased activated protein C: protein C inhibitor complex and decreased protein C inhibitor levels in patients with chronic renal failure on maintenance hemodialysis. 1072 91

Monocyte tissue factor expression is supposed to play an important role in the hypercoagulability of blood in cancer patients. The relation between coagulation parameters and the expression of monocyte membrane proteins involved in hemostasis or monocyte activation was studied in 21 patients with a disseminated malignancy and 21 age- and sex-matched healthy controls. In the cancer patient group no increase of monocyte tissue factor expression was found (8. 4% vs. 7.8%; P = 0.83), but a significant increase of monocyte-bound activated protein C (APC) (28.8% vs. 13.4%; P = 0.009) and monocyte CD16 expression (34.5% vs. 27.0%; P = 0.007) was observed. There was also a significant increase of D-dimers (2.0 vs. 0.2 microg/ml; P = 0.001), a decrease of antithrombin (83.5% vs. 102.0%; P = 0.004), but no increase of TAT complexes (1.7 vs. 1.5 microg/l; P = 0.38) or factor VII(a) (68.5% vs. 75.0%; P = 0.52). The increase of D-dimers was significantly correlated with the monocyte APC (R = 0.60; P = 0. 005), but not with monocyte tissue factor levels (R = -0.22; P = 0. 35) or TAT complexes (R = 0.12; P = 0.60). These results reflect a local rather than systemic thrombin and fibrin formation. It is suggested that the APC formed locally enters the circulation and binds to peripheral blood monocytes. APC bound on monocytes is known to inhibit monocyte cytokine production and might therefore be involved in regulatory responses of monocytes in cancer patients.
 ...
PMID:Increased D-dimer levels correlate with binding of activated protein C, but not tissue factor expression, on peripheral blood monocytes in cancer patients. 1091 81

Thrombomodulin (TM), a membrane-bound receptor for thrombin on the endothelial cell surface, contributes to the regulation of the coagulation system. TM is known to exist in human plasma and urine as soluble forms. We purified soluble TM from human urine (MR-33) and investigated the anticoagulant effects of MR-33 in vitro and in vivo. In human plasma, MR-33 inhibited not only the procoagulant activity of thrombin, but also the thrombin generation via accelerating the thrombin-catalyzed protein C activation. In rat disseminated intravascular coagulation (DIC) models, intravenous infusion of MR-33 improved the hematological abnormalities without excessive prolongation of APTT and bleeding time. Benefit (dose required for 50% inhibition of fibrinogen decrease: ED50) to risk (minimum dose required for significant prolongation of bleeding time) ratio was 1:27 for MR-33. Furthermore, the anticoagulant activities of MR-33 was independent of AT III activity, and MR-33 was effective on heparin-resistant DIC models with low AT III level in rats. Intravenous injection of MR-33 prevented the endotoxin-induced increases in TAT, TNF-alpha and IL-6 level and pulmonary vascular permeability in mice. These results indicate that MR-33 may be a clinically useful antithrombotic agent with reduced risk for hemorrhage, and this drug also has anti-inflammatory effects. Clinical trials of MR-33 for the treatment of DIC are now in progress in Japan.
 ...
PMID:[Thrombomodulin]. 1121 78

Routine hemostatic laboratory tests lack sensitivity and are of little value in the detection of the pregnancy associated hypercoagulable conditions. Assays for F 1 + 2, AT levels, TAT complex, APC activity, FPA, D-Dimers, tPA, plasminogen, PAI 1, and PAI 2 are more specific for fibrin formation and lysis. Monitoring these tests along with fibrinogen and platelet counts provides important information for the early detection of hemostatic activation and for monitoring the severity of the condition. Early detection and therapy is essential for limiting the deleterious complications of pregnancy. Advances in research, the development of new tests such as the TM assay and gene analysis, as well as highly skilled personnel, are required for the providing of quality pre and postnatal healthcare.
 ...
PMID:Hemostatic changes associated with normal and abnormal pregnancies. 1158 9

Our newly devised immunofluorometric sandwich assay for measuring plasma concentrations of activated protein C (APC) in complex with protein C inhibitor (PCI) was compared with testing for conventional markers of myocardial damage CKMB (creatine kinase MB), TNI (troponin I) and hypercoagulability (D-dimer, TAT) in 76 patients with suspected myocardial infarction (MI). APC-PCI complex levels in samples drawn on admission did not correlate with CKMB in the simultaneously drawn sample but correlated closely with maximal CKMB, which reflects MI size (r = 0.52). The areas under the receiver operating characteristics (ROC) curves calculated for the APC-PCI complex results obtained upon admission did not differ significantly from the corresponding values for CKMB, TNI or TAT. Our results show that in patients at risk for MI, the APC-PCI concentration is a sensitive and independent marker that can identify a subgroup of MI patients with normal CKMB but an increased APC-PCI level upon admission. It remains to be determined whether these patients would benefit from early intensive anticoagulant treatment.
 ...
PMID:A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes. 1168 37


<< Previous 1 2 3 Next >>