Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UE34 (fibrinogen)
 30,244 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of simultaneous infusions of low-dose recombinant tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, pro-urokinase) on coronary arterial thrombolysis was investigated in 23 patients treated within 6 hours (mean 2.6 +/- 1.1, range 1.2 to 5.9) of symptoms of an acute myocardial infarction. Infarct artery patency at 90 minutes was achieved in 16 (70%, 95% confidence limits of 0.47 to 0.87) of 23 patients after a 1-hour intravenous infusion of 20 and 16.3 mg of t-PA and scu-PA, respectively. At 90 minutes, the fibrinogen concentration decreased from 369 +/- 207 to 316 +/- 192 mg/dl (p = not significant), while plasminogen decreased to 69 +/- 24% (p = 0.001) and alpha-2-antiplasmin to 77 +/- 24% (p = 0.001) of pretreatment values. Although no bleeding requiring termination of drug infusion or transfusion occurred, 1 patient with cerebrovascular amyloidosis had a fatal intracerebral hemorrhage. These findings suggest that combination therapy may allow substantial reductions in total thrombolytic doses while still achieving effective fibrin-specific coronary thrombolysis.
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PMID:Clot-selective coronary thrombolysis with low-dose synergistic combinations of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator. The Pro-Urokinase for Myocardial Infarction Study Group. 174 55

The prevalence of inherited thrombotic syndrome in the general population appears to be higher than that of inherited bleeding disorders. The most important candidates for screening are patients with unexplained venous thromboembolism at ages of less than 40 years: In 18 children and adolescents suffering from "idiopathic" vein thrombosis laboratory screening has been performed: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin. Compared to an age matched healthy control group in children with idiopathic vein thrombosis we could demonstrate in vitro platelet activation with significant enhanced platelet aggregation and elevated levels of von Willebrand factor in the onset of the disease. Antithrombin III, protein C, alpha-2-antiplasmin and alpha-2-macroglobulin were significantly decreased. These changes turned to be normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, alpha-1-antichymotrypsin and c1-inactivator showed no alterations compared to the control. Platelet activation and alteration of platelet function in vivo and in vitro is established to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The decreased inhibitors of the hemostatic system antithrombin III and protein C in the onset period of thrombotic diseases are discussed to be an increased turnover, whereas the decreased levels of alpha-2-antiplasmin and alpha-2-macroglobulin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.
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PMID:[Hemostatic changes in idiopathic venous thrombosis in childhood and adolescence]. 175 45

Eighteen patients with chronic renal failure due to primary glomerular disease undergoing conservative treatment (CRF patients) were studied to evaluate whether coagulation and fibrinolytic activity in plasma are enhanced in the patients. We measured plasma levels of coagulation-fibrinolysis parameters including thrombin-antithrombin III complex (TAT) (an index of thrombin formation), alpha 2-plasmin inhibitor (alpha 2 PI)-plasmin complex (alpha 2 PIC) (an indicator of plasmin production) and cross-linked fibrin degradation products (XL-FDP) (an index of fibrinolysis secondary to coagulation). There was no correlation between plasma levels of TAT, alpha 2PIC and XL-FDP and serum creatinine levels in CRF patients. Both fibrinogen and TAT were found to be significantly higher in CRF patients than in normal controls. TAT was negatively correlated with serum albumin or total protein. Antithrombin III (ATIII) activity was significantly lower in CRF patients than in normal controls. CRF patients showed significantly but slightly higher alpha 2 PIC and XL-FDP when compared to normal controls. These results suggest that TAT, alpha 2PIC and XL-FDP are good indicators of coagulation-fibrinolysis even in patients with decreased renal function. Coagulation activity is significantly increased in CRF patients but fibrinolysis secondary to coagulation is only slightly enhanced.
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PMID:Coagulation and fibrinolysis in patients with chronic renal failure undergoing conservative treatment. 177 41

Desmopressin acetate (DDAVP) is known to stimulate the release of tissue-type plasminogen activator (t-PA) from endothelial cells, but it is unclear whether the increased t-PA actually elicits the plasmin generation and fibrin(ogen)olysis in the circulating blood. We measured plasma levels of plasmin-alpha 2-plasmin inhibitor complex, fibrinogen degradation products (FgDP) and fibrin degradation products (FbDP) following desmopressin infusion in 19 patients with bleeding disorders or thrombophilia. Administration of desmopressin (0.3-0.4 microgram/kg) produced a 4.0-fold increase in plasmin-alpha 2-plasmin inhibitor complex at 30 min, whereas neither FgDP nor FbDP was elevated significantly. These findings indicate that desmopressin infusion provokes the generation of plasmin in vivo, but most of the plasmin generated is complexed to alpha 2-plasmin inhibitor and does not degradate fibrin or fibrinogen.
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PMID:Plasmin generation and fibrin(ogen)olysis following desmopressin infusion. 182 8

To elucidate the etiology of the thrombogenic effects of high-dose medroxyprogesterone acetate (MPA) in the treatment of breast cancer, hematologic parameters were sequentially assessed in 12 patients receiving MPA 800 mg p.o. daily for 6 months as adjuvant hormone therapy after mastectomy. The results were as follows. (1) Coagulation system: levels of factor VII and fibrinogen decreased significantly, whereas factors II and IX increased significantly, with a shortened activated partial thromboplastin time. (2) Fibrinolytic system: plasminogen and alpha 2-plasmin inhibitor-plasmin complex increased, whereas fibrinogen degradation products remained low. (3) Anticoagulation system: antithrombin III increased significantly. (4) These changes were most marked after 2 or 4 weeks of MPA treatment, and returned to the pretreatment level one month after discontinuation of treatment. (5) No patients in this study developed thromboembolic disease during or after MPA administration. These results indicate that MPA may induce a hypercoagulable state, but this state does not directly lead to the development of thrombosis.
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PMID:Changes in hematologic parameters during treatment with medroxyprogesterone acetate for breast cancer. 182 63

Segmentally enclosed thrombolysis (SET) was performed immediately following 34 percutaneous transluminal angioplasties (PTAs) for femoropopliteal occlusions. The dilated segment was sealed off with a double balloon catheter, and recombinant tissue plasminogen activator (rt-PA) 1 mg/ml and heparin 200 IU/ml were injected between the balloons. The catheter was removed after 30 min and heparin treatment was continued for 24 h. Alpha-2-antiplasmin was initially reduced by 13% and normalized 2 h after SET, indicating that only small amounts of free plasmin were liberated during thrombolysis. No clinically relevant changes in plasma fibrinogen occurred. Two puncture site hemorrhages did not coincide with the coagulopathy induced by SET. One-year patency was 80%. Early rethrombosis occurred in 9% versus 41% in our previous series on standard PTA for femoropopliteal occlusions (p less than 0.001). Therefore, SET is considered beneficial in reducing the incidence of early rethrombosis.
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PMID:Segmentally enclosed thrombolysis in percutaneous transluminal angioplasty for femoropopliteal occlusions: a report from a pilot study. 183 37

Plasma concentration of fibrinogen (Fbg), plasminogen (PLG), antithrombin III (AT III), alpha 2-plasmin inhibitor (alpha 2-PI), thrombin antithrombin III complex (TAT) and plasmin alpha 2-plasmin inhibitor complex (PIC) were evaluated in 23 nephrotic patients with proteinuria more than 3.5 g/day, including 4 cases with clinical evidence of thromboembolism. Among patients without thromboembolism, concentration of PLG and AT III was in the normal range but that of Fbg and alpha 2-PI was significantly elevated (p less than 0.01 for Fbg and p less than 0.001 for alpha 2-PI respectively). Also there was a positive relationship between AT III and serum albumin (p less than 0.05). Two fifth of these patients had an had an increased level of TAT, and also had a higher level of PIC compared with normal control (p less than 0.01). There was a positive relationship between TAT and PIC, TAT and Fbg (p less than 0.05), PIC and Fbg (p less than 0.01). TAT and PIC levels were markedly elevated in the patients with thromboembolism. From aforementioned data, it was suggested that patients with nephrotic syndrome would be in the prethrombotic state and the increased level of Fbg is one of the major risk factors of thromboembolic complications in these patients. Furthermore measurement of TAT and PIC are the useful means for the diagnosis of these complications.
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PMID:[Concentration of thrombin antithrombin III complex and plasmin alpha 2-plasmin inhibitor complex in nephrotic syndrome]. 183 41

Effects of low molecular weight heparin (FR-860) on experimental disseminated intravascular coagulation (DIC) models in rats were compared with those of conventional unfractionated heparin (UF-heparin) and other anticoagulants. In the endotoxin-induced DIC model, FR-860 (12.5-200 U/kg/hr) and UF-heparin (25-200 U/kg/hr) inhibited dose-dependently the decreases in platelet counts, fibrinogen, antithrombin III activity and alpha 2-plasmin inhibitor activity, and they also inhibited the increases in fibrin de-products and thrombus formation in the glomerular capillary bed. Neither gabexate mesilate (FOY, 10 mg/kg/hr) nor nafamostat mesilate (FUT, 0.1 mg/kg/hr) improved endotoxin-induced DIC. FR-860 showed comparable potency to UF-heparin in plasma anti-factor Xa (F.Xa) activity. However, FR-860 was weaker than UF-heparin in prolongation of activated partial thromboplastin time. In the thrombin-induced DIC model, both FR-860 and UF-heparin significantly improved, as seen in the endotoxin-induced DIC model, the changes in coagulation and fibrinolytic parameters and suppressed the production of pulmonary thrombus. On the other hand, both FOY and FUT showed significant but weak improvement in this model. In addition, FR-860 inhibited the enhancement of fibrinolysis and the production of pulmonary thrombus in the lactic acid-induced DIC model. These results suggest that the efficacy of FR-860 on DIC in rats is comparable to that of UF-heparin and that the efficacy can be attributed to its anti-F.Xa activity. FR-860 can be expected to be a useful therapeutic drug for DIC.
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PMID:[Effects of low molecular weight heparin (FR-860) on the experimental disseminated intravascular coagulation models]. 188 62

Intravenous administrations of 2000 x 10(4)IU (33 mg) (rt-PA2) and 3000 x 10(4)IU (50 mg) (rt-PA3) of a new recombinant tissue plasminogen activator (rt-PA:TD-2061) derived from uterine endothelial cells and urokinase (UK) 96 x 10(4)IU were compared in a double blind, randomized trial of 198 patients with evolving myocardial infarction. All patients entered the trial within 6 h of the onset of symptoms and underwent baseline coronary angiography of the infarct-related coronary artery before thrombolytic therapy was instituted. Sixty minutes following thrombolytic therapy occluded infarct-related arteries were successfully reperfused in 41.5% of 66 patients in the UK, 76.4% of 72 patients in the rt-PA2, and 74.6% of 59 patients in the rt-PA3 group. Statistically significant differences were observed between the UK and rt-PA groups (p less than 0.01). Serum fibrinogen levels declined in all 3 groups at 60 min post-therapy by averages of 35.9 +/- 3.1% in the UK, 16.8 +/- 4.8% in the rt-PA2 and 17.5 +/- 4.5% in the rt-PA3 group. The difference between the UK and the rt-PA groups was statistically significant (p less than 0.01). Plasma plasminogen and alpha 2-plasmin inhibitor levels showed the same tendencies. Bleeding was the most commonly observed complication and was most commonly seen at the catheterization site. There was no difference in the incidence among the 3 groups. Hospital deaths occurred in 5.3%, 6.3%, and 4.7% of the cases in the UK, rt-PA2 and rt-PA3 groups, respectively. We conclude, therefore, that rt-PA achieves a significantly higher rate of recanalization with less extensive systemic fibrinogenolysis at the dose employed than does UK. The optimum intravenous dose of rt-PA for Japanese patients is considered to be 2000 x 10(4)IU (33 mg).
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PMID:Intravenous recombinant tissue-type plasminogen activator (rt-PA) and urokinase (UK) in patients with evolving myocardial infarction--a multicenter double-blind, randomized trial in Japan. 190 67

There are many factors influencing the growth of the fetus. Since these factors have complex interrelations, they are difficult to clarify. The authors studied the effects of blood coagulation and fibrinolysis on the growth of the fetus during pregnancy, especially from the 2nd trimester into the 3rd trimester. The subjects were 86 normal pregnant women, and the subjects of study were blood coagulation, fibrinolysis activity of the mother, and estimated fetal birth weight after the 28th (2nd trimester) and 36th weeks of gestation (3rd trimester) in each case. 1. Changes in blood coagulation activity and fibrinolysis varied from the 2nd trimester into the 3rd trimester. The percentage of cases showing lowered platelets was 68.6% of the total, and the percentages of cases with reduced platelet ADP, epinephrine, and collagen aggregation were 60.5%, 55.8%, and 51.2%, respectively. The percentages of cases showing shortened prothrombin time and activated partial thromboplastin time were 58.1% and 51.2% of the total, respectively. The percentage of cases with reduced fibrinogen was 24.4% of the total. The percentages of cases with reduced antithrombin III, plasminogen, and alpha 2-plasmin inhibitor activity were 66.3%, 55.8%, and 75.6% of the total, respectively. 2. The birth weight of babies in a group with shortened prothrombin time was 2,935.1 +/- 395.2g(n = 50, mean +/- SD), while that in a group with prolonged prothrombin time was 3,106.2 +/- 357.9g(n = 36). The estimated fetal birth weight gain from the 2nd trimester to the 3rd trimester was 1,431.6 +/- 296.5g in the former group and 1,644.5 +/- 390.5g in the latter group. The differences were significant (p less than 0.05, p less than 0.01). The birth weight of babies in a group with lowered antithrombin III activity was 2,960.1 +/- 341.3g(n = 57), and that in an acceleration group was 3,157.8 +/- 370.0g(n = 29). The estimated fetal weight gain from the 2nd trimester to the 3rd trimester was 1,477.7 +/- 281.9g in the former group and 1,637.1 +/- 390.6g in the latter group. The differences were significant (p less than 0.02, p less than 0.05). 3. The estimated fetal weight gain from the 2nd trimester to the 3rd trimester in the group showing prolongated prothrombin time and activated partial thromboplastin time in this period was significantly larger than in the group showing shortened prothrombin time and activated partial thromboplastin time (p less than 0.001). These results suggested that the changes in blood coagulation and fibrinolysis activity of mothers from the 2nd trimester to the 3rd trimester affected the growth of the fetus.
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PMID:[Blood coagulation and fibrinolysis activities during normal pregnancy and fetal growth--study based on estimated fetal body weight]. 191 80


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