Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with liver disease frequently have hemostatic abnormalities which include accelerated fibrinolysis. In order to assess the fibrinolytic state in liver disease, plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP), and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 36 patients with liver disease (six patients with acute hepatitis, seven with chronic hepatitis, ten with liver cirrhosis, 11 with hepatocellular carcinoma, and two with intrahepatic cholestasis). As compared with healthy subjects, mean plasma levels of FbDP (1,083 +/- SD 1,254 vs. 236 +/- 100 ng/ml, P = 0.005) and TDP (1,773 +/- 1,814 vs. 669 +/- 212 ng/ml, P = 0.001) were significantly elevated in patients with liver disease, whereas FgDP was normal (389 +/- 202 vs. 396 +/- 132 ng/ml, P = 0.87). Plasma FbDP correlated very well with TDP (r = 0.986, P less than 0.00001) in liver disease. In addition, FbDP and TDP but not FgDP correlated with plasma concentrations of thrombin-antithrombin III complex. When plotted by the disease categories, the magnitude of elevations of FbDP and TDP was the most prominent in acute hepatitis followed by hepatocellular carcinoma. These findings indicate that activation of fibrinolysis occurs following thrombin generation, but increased primary fibrinogenolysis is rare in liver disease.
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PMID:Fibrinolysis and fibrinogenolysis in liver disease. 219 67

In order to assess precisely the fibrinolytic state in disseminated intravascular coagulation (DIC), plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP) and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 72 patients with DIC at presentation. Not only FbDP and TDP but also FgDP were markedly elevated in patients with DIC. When analyzed according to the underlying disease categories, the relative proportion of FgDP to TDP was high in patients with acute promyelocytic leukemia and vascular diseases, and it was the lowest in patients with sepsis. Correlation analysis revealed that plasma levels of FgDP correlated negatively with alpha 2-antiplasmin and positively with plasmin-alpha 2-antiplasmin complex (PAP) and a ratio of PAP to thrombin-antithrombin III complex (TAT). These findings indicate that besides fibrinolysis, fibrinogenolysis is markedly accelerated in the majority of the patients with DIC.
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PMID:Fibrinolysis and fibrinogenolysis in disseminated intravascular coagulation. 240 38

Pregnancy is characterized by plasmatic variations of coagulative factors' concentration and by different haemostatic-fibrinolytic balance. At present it is possible, with EIA methods, to measure fibrinogen (FgDP) and fibrin (FbDP) degradation products with precision and accuracy, as direct indexes of fibrinolysis and the thrombin-antithrombin III complex (TAT) as indirect index of thrombophilia. We have considered the course of those indexes in 61 pregnant women within the tenth week of gestation, before and after voluntary pregnancy interruption (VPI) resulted without complications. The results don't show any peculiar variation of the examined parameters between the pregnant women before VPI and a control group. Comparing the basal data with those obtained three hours after VPI, all indexes are increased, particularly FbDP. After 24 hours the concentration of FgDP, FbDP and TDP decreased in comparison with the three hours control drawing, nevertheless staying higher than the values obtained in the basal drawing. The evolution of FDP and of TAT, in our study, points out that, in the first weeks of pregnancy, the haemostatic-fibrinolytic balance does not differ significantly from the physiological balance. Three hours after VPI fibrinolytic mechanisms prevail as regards the fibrinogenolytic ones. TAT increases after 3 hours and returns to the rules after 24 hours, proposing itself as an indirect index of thrombinic activation and as a direct index of antithrombinic activity.
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PMID:[Modifications induced on thrombin and plasmin activity by voluntary interruption of pregnancy]. 835 Oct 63

We studied the stability of three markers of coagulation (prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), and soluble fibrin (SF)) in stored frozen plasma, in addition to one marker of fibrinolysis (total fibrinogen degradation products and fibrin degradation products (TDP)). All markers were measured using enzyme linked immunosorbent assays (ELISA). None of the markers changed significantly after initial freezing. F1 + 2 in plasma was stable following storage at -80 degrees C for 3 months. In plasma containing high SF levels stored at -80 degrees C, an insignificant time dependent trend towards decreasing plasma values was observed. TAT levels in plasma decreased significantly following 3 months at -80 degrees C. TDP levels in plasma showed some fluctuation when stored in freezer. Our results suggest that careful observation of the long time storage stability of protein components is demanded in clinical research.
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PMID:Short-time stability of markers of coagulation and fibrinolysis in frozen plasma. 882 40

Erythromelalgia, a characteristic aspirin-responsive microvascular thrombotic complication in essential thrombocythemia (ET), may develop despite oral anticoagulant treatment or treatment with heparin, suggesting that the generation of thrombin is not a prerequisite for its development. To study this, a cross-sectional comparison of the plasma levels of thrombomodulin (TM), platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), prothrombin fragment 1 + 2 (F1 + 2) and total degradation products of fibrin(ogen) (TDP) was made between 5 ET patients suffering from erythromelalgia, 16 asymptomatic ET patients and 20 control subjects, and after treatment with aspirin, respectively. Furthermore, 2 ET patients with a history of erythromelalgia were studied at regular time intervals after discontinuation of aspirin until erythromelalgia recurred. As compared with asymptomatic ET patients and control subjects erythromelalgia was characterized by significantly higher beta-TG and TM levels but no significant differences were detected in either F1 + 2 or TDP levels. Treatment of erythromelalgia with aspirin resulted in disappearance of erythromelalgic signs and symptoms, which was paralleled by a significant decrease of beta-TG and TM levels. Histopathologic and immunohistochemical analysis of biopsies derived from erythromelalgic skin areas of 2 ET patients showed that erythromelalgic thrombi stained positively for von Willebrand factor opposed to only a weak fibrin staining. Our data suggest that erythromelalgia is caused by the intravascular activation and aggregation of platelets with subsequent sludging or occlusion of the acral arterial microvasculature. The generation of thrombin appears not to be essential for the formation of these platelet thrombi, thereby giving a plausible explanation for the inefficacy of coumadin derivatives and heparin in the prevention and treatment of erythromelalgia in essential thrombocythemia.
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PMID:Erythromelalgia in essential thrombocythemia is characterized by platelet activation and endothelial cell damage but not by thrombin generation. 888 66

This study was carried out in order to compare the coagulation balance in patients with colorectal cancer before and after surgical removal of tumor with an age matched non-malignancy control group. Furthermore, it was studied whether preoperative coagulation state in cancer patients was correlated to the postoperative development of deep venous thrombosis (DVT) diagnosed by venography. Plasma was collected preoperatively in 93 cancer patients and 30 controls, and postoperatively on day one, two, seven, and ninety in 88 cancer patients and 18 controls. Prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and total fibrin(ogen) degradation products (TDP) were quantitated in plasma by enzyme linked immunosorbent assays (ELISA). As compared to controls, patients admitted for cancer treatment displayed significantly higher levels of F1 + 2 and TAT. Patients suffering from advanced colorectal cancer had significantly higher levels of TAT and TDP as compared to patients with localized colorectal cancer. Twenty-three percent of cancer patients developed DVT postoperatively. Preoperatively these patients displayed significantly higher TDP levels, and postoperatively higher levels of F1 + 2, TAT, and TDP compared to cancer patients without DVT. The marked activation of blood coagulation and fibrinolysis observed in all patients following major abdominal surgery was even more pronounced in patients not cured for cancer.
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PMID:Pre- and postoperative state of coagulation and fibrinolysis in plasma of patients with benign and malignant colorectal disease--a preliminary study. 890 90

We measured the ability of the thrombin receptor activating peptide, SFLLR-NH2 (P5A) to stimulate 3H-thymidine incorporation in hamster CCL-39 fibroblasts either alone or in combination with the thrombin-derived polypeptides, YPPWNKNFTENDLL (TDP-1) and AGYKPDEGKRGDACEGDSGGPFV (TDP-2). In the presence (but not absence) of the amino peptidase inhibitor amastatin (10 microM), P5A alone (7.5 to 100 microM) caused a 1.5- to 2-fold stimulation of thymidine incorporation above basal, even though this inhibitor did not abrogate the degradation of P5A by other peptidases present in the assay medium. Neither TDP-1 nor TDP-2 alone had any effect on thymidine incorporation. However, TDP-1 (30 to 90 microM) considerably augmented P5A-mediated thymidine incorporation at low P5A concentrations (7.5 to 30 microM), shifting the P5A concentration-effect curve to the left. TDP-2 was inactive in this regard. The EC50 for this potentiating action of TDP-1 was approximately 40 microM. Further, thrombin, rendered proteolytically inactive by a low-molecular-weight bifunctional inhibitor, hirutonin-6, also acted synergistically with P5A to stimulate CCL-39 cell thymidine incorporation. We hypothesize that thrombin can cause its cellular effects, such as thymidine incorporation, not only via the proteolytic activation of its G-protein-coupled receptor, but also via the concurrent and synergistic interaction of its TDP-1 peptide domain with a separate cell surface docking site.
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PMID:Synergistic actions of a thrombin-derived synthetic peptide and a thrombin receptor-activating peptide in stimulating fibroblast mitogenesis. 895 98

Type 2 diabetes mellitus is frequently accompanied by hypercoagulability and hypofibrinolysis. Both are related to increased cardiovascular risk, but possibly with endothelial injury as well. Studies with nondiabetic persons indicate that unopposed oestrogen replacement therapy (oERT) decreases cardiovascular risk, possibly mediated in part by effects on coagulation and fibrinolysis. In a double-blind, randomised placebo-controlled trial, we assessed the effect of oral 17 beta-oestradiol daily during 6 weeks on indicators of coagulation and of fibrinolysis in postmenopausal women with type 2 diabetes mellitus. We observed significant increases of Factor VII (FVII) and von Willebrand factor (vWF) after oERT and no change in the already high fibrinogen. Prothrombin fragment 1 + 2 (F1 + 2) increased after oERT, whereas thrombin-antithrombin (TAT) complexes was unchanged, but increments of F1 + 2 and TAT correlated. Soluble fibrin (SF) levels remained stable. In fibrinolysis, a clear reduction in plasminogen activator inhibitor 1 (PAI-1) was observed, but no significant change in tissue-type plasminogen activator antigen (t-PA-Ag) or activity was found, although fibrinolytic activity assessed as t-PA activity (t-PA-Act) tended to increase after oERT. Indicators of fibrinolytic activity (plasmin-antiplasmin complexes and fibrin degradation products) however did not change. oERT increased C-reactive protein (CRP) but none of the coagulation or fibrinolysis changes significantly associated with the CRP changes. It is concluded that oERT increases the coagulation potency as well as the fibrinolytic potency raising the question of the net effect in their balance. Increase in F1 + 2 suggests that in diabetic women oERT effectively increases the chronic, continuous activation of coagulation, which appears to be compensated for or not effective in the blood compartment as judged from the unchanged levels of SF. Suspected increased fibrin formation in the vascular wall is at least not followed by increases in fibrinogen degradation products (TDP), which suggests the possibility of accumulation and increased cardiovascular risk. The results indicate that specific attention should be paid to fibrin turnover in studying other categories of women and the effects of the addition of progesterone.
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PMID:The effect of 17 beta-oestradiol on variables of coagulation and fibrinolysis in postmenopausal women with type 2 diabetes mellitus. 1261 82