Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fibrinolytic system plays an important role in the physiological maintenance of blood flow and the dissolution of thrombi. Administration of fibrinolytic agents in indications such as myocardial infarction, pulmonary embolism, deep vein thrombosis or stroke, therefore, offers a rational means to dissolve pathological thrombi and restore vascular patency. The functional domains of the physiological tissue plasminogen activator (t-PA) provide fibrin specificity and serine protease activity for plasminogen cleavage and binding to liver receptors which gives the molecule a short half-life. In order to combat acute thromboembolic events such as myocardial infarction, the structure of the natural t-PA molecule was genetically modified to prolong its half-life, to increase its fibrin-specificity and to improve its resistance to plasminogen activator inhibitor. These features of TNK-t-PA allow bolus administration in emergency situations, early reperfusion of the blood vessel and a low rate of bleeding complications, thus improving the overall benefit to patients.
 ...
PMID:Improving natural principles with genetic engineering: TNK-tissue plasminogen activator. 1145 85

Since the first patient with antithrombin deficiency was reported, various hereditary thrombophilia have been discovered. However, we experienced a family line of multiple thrombosis in which known hereditary thrombophilia were all refuted. Case 1 died of inferior vena cava thrombosis at the age of 56 days. Case 2, the elder sister of Case 1, developed deep vein thrombosis of the left leg at age 2. She was started on warfarin but contracted deep vein thrombosis of the right leg at the age of 7. In the family of these cases there have been another five cases of thrombosis, spanning three generations, giving a total of seven cases. Six of the cases developed at an early age, below 50 years. Antithrombin, protein C, protein S, heparin cofactor II, soluble thrombomodulin, plasminogen, alpha 2 plasminogen inhibitor, and tissue factor pathway inhibitor were measured but there were no abnormalities, nor was there any resistance to activated protein C. The onset of thrombosis in this family is becoming younger with the passing of generations, and clinical symptoms have been showing a worsening tendency.
 ...
PMID:[A family with multiple thrombosis including infancy occurrence]. 1157 53

To clarify the possible role of persistent thrombocytosis after splenectomy as being a predisposing factor causing thromboembolism. Blood coagulation profiles were studied in 35 patients (20 M and 15 F, mean age 42 +/- 17.5) suffering from thrombocytosis (> 500,000/dl) who underwent splenectomy for non-malignant and non-traumatic diseases. Seventy healthy subjects acted as a control group. Tests were performed 6 months after the operation and for both groups (patients and controls) blood samples were collected for: platelets, fibrinogen, PT, APTT, AT III, plasminogen, F1 + 2, t-PA and DNA analysis for F V, F II and MTHFR. After one year all subjects were controlled for thrombocytosis, genomic abnormalities and venous thrombosis. All the analyses were performed according to the Statistical Package for Social Science. The significance of the differences in means was evaluated by non-parametric tests, differences with a P value < 0.05 being considered significant. Increased plasma levels of fibrinogen, D-dimer, F1 + 2 and PAI-1 were found in the patients compared with the control group. TPA was significantly lower in the patients than in the controls. At the one year follow-up, two patients with genetic polymorphism had suffered deep venous thrombosis. Our findings indicate that splenectomy contributes to abnormal platelet aggregation and endothelial cell activation with hypercoagulability.
 ...
PMID:[Blood coagulation changes in patients with post-splenectomy persistent thrombocytosis]. 1158 73

Thrombolytic agents are in widespread use for the dissolution of arterial and venous pathologic thrombi. Clinical settings where thrombolysis has played an important role include the acute coronary syndromes, peripheral arterial occlusion, ischemic stroke, deep venous thrombosis, and pulmonary embolism. Thrombolytic agents have been successfully employed in each of these areas, achieving dissolution of the occluding thrombus, reconstitution of blood flow, and improvement in the status of the tissue bed supplied or drained by the involved vascular segment. All clinically available thrombolytic agents act through cleavage of the plasminogen molecule to its active form, plasmin. Despite this similar mechanism of action, the thrombolytic agents differ in several biochemical parameters, including fibrin specificity, fibrin affinity, and relative resistance to inactivating factors in the plasma. Whether these differences account for significant differences in clinical outcome is a matter of some dispute. It is quite possible that in vitro biochemical differences do not have meaningful clinical correlates. However, there exists some evidence to suggest that differences in the risk of distant hemorrhage, idiosyncratic reactions, and the rapidity of clot dissolution do exist. An ideal agent for peripheral vascular thrombolysis would be one that was specific in its actions at the site of pathologic thrombi yet left the important and desirable pathologic thrombi that seal vascular defects unscathed. Although such an agent has not yet been identified, an understanding of the mechanism of action and principles underlying pharmacologic thrombolysis provides the necessary foundation of knowledge to choose a particular thrombolytic agent for a given clinical scenario.
 ...
PMID:Comparison of safety and efficacy of the various thrombolytic agents. 1255 39

Plasminogen is a key proenzyme in the fibrinolytic and thrombolytic systems. Congenital deficiency of plasminogen and molecular abnormality of plasminogen (dysplasminogenemia) have been reported in association with the thrombotic tendency in human. In dysplasminogenemia, the level of immunoreactive plasminogen is normal, although the functional activity is reduced. Human plasminogen gene spans about 52.5 kb of DNA and consists of 19 exons. Three types of mutations (Ala601Thr, Val355Phe, and Asp676Asn) have been described in dysplasminogenemia. In this study, we measured the plasminogen activity in patients with deep vein thrombosis and analyzed the DNA sequence to detect three point mutations (Ala601Thr, Val355Phe and Asp676Asn) in patients with hypo/dysplasminogenemia. Dysplasminogenemia was identified in 3 (8.3%) of unrelated 36 patients with deep vein thrombosis and the Ala601Thr mutation was detected in all three patients with dysplasminogenemia. In conclusion, dysplasminogenemia is not rare in deep vein thrombosis, which suggests a risk factor for the thrombosis in Korean population.
 ...
PMID:Detection of an Ala601Thr mutation of plasminogen gene in 3 out of 36 Korean patients with deep vein thrombosis. 1269 11

We assessed the clinical status after anticoagulant therapy in acute deep vein thrombosis (DVT) involving the lower limbs. Between 1994 and 2001, 139 patients suffering from acute DVT were treated with heparin therapy followed by oral anticoagulant therapy. The coagulation factor assay was done prior to any anticoagulation therapy. The duplex scan was checked serially. The mean follow-up periods was 32 +/- 19 months. There were 32 (23.0%)cases of protein C deficiency, 12 (8.6%) cases of protein S deficiency, 13 (9.4%) cases of AT-III deficiency and 11 (7.9%) cases of abnormal plasminogen level. Fourteen cases had coagulation factor abnormalities within the family. The initial lung scan showed 29 (20.9%) cases with high, 13 (9.4%) cases with intermediate and 70 (50.4%) cases with a low probability of pulmonary embolism (PE) developing. During the follow-up periods, there were 3 cases of non-fatal PE documented with chest CT scan. The patients were divided according to the extent of the thrombus; Group I (38 cases) was limited to the infrainguinal deep vein, Group II (70 cases) extended to the iliac vein and Group III (9 cases) extended to the vena cava. Partial lysis occurred in 20/35/3 (52.6/50.0/33.3%) cases and no change in 10/24/6 (26.3/ 34.3/ 66.7%) cases in Groups I/ II/ III, respectively. Deep vein valvular reflux occurred in 15/25/5 (39.5/35.7/55.6%) cases in Groups I/ II/ III, respectively. With anticoagulation therapy, most of the thrombi remained in unresolved states and there was a high rate of deep vein valvular reflux. However, there was no serious complications which affected the patients' quality of life.
 ...
PMID:Clinical and functional assessment after anticoagulant therapy of acute deep vein thrombosis involving the lower limb. 1295 Jan 26

Reduced plasminogen activity with a normal level of antigen is commonly observed in Japanese individuals. The first reported patient with plasminogen deficiency was accompanied with deep vein thrombosis. The present study examines whether heterozygous or homozygous deficiency of plasminogen is a risk factor for thrombotic disease. This study measures the plasminogen activity of 4517 individuals in the general population, determines the cut-off to define plasminogen deficiency, and identifies plasminogen deficiencies in the control groups and thrombotic disease groups. In another study, we examined the phenotypes of consecutive patients with homozygous plasminogen deficiency detected in our hospital. We found 173 and two of 4517 individuals to have heterozygous and homozygous deficiency with normal plasminogen antigen level, respectively, and 19 to have heterozygous deficiency with reduced antigen levels. The incidence of plasminogen deficiency in an age- and sex-matched control group (13/324, 4.01% for deep vein thrombosis or 13/330, 3.94% for stroke) selected from the 4517 individuals was not significantly different from those in patients with deep vein thrombosis (3/108, 2.78%) or cardioembolic stroke (6/110, 5.55%). Among 19 patients with homozygous plasminogen deficiency showing about 10% plasminogen activity, none had deep vein thrombosis. These findings indicate that neither heterozygous nor homozygous plasminogen deficiency constitutes a significant risk factor for thrombotic disease.
 ...
PMID:Population-based distribution of plasminogen activity and estimated prevalence and relevance to thrombotic diseases of plasminogen deficiency in the Japanese: the Suita Study. 1462 75

Over the past two decades tissue-type plasminogen activator (t-PA), the main physiological plasminogen activator, has been developed as a fibrin-specific thrombolytic agent for the treatment of various thromboembolic diseases. Milestones in this development include: first purification of human t-PA from uterine tissue, elucidation of the interactions regulating physiological fibrinolysis, thus providing a molecular basis for the concept of fibrin-specific plasminogen activation, first animal models of thrombosis and pilot studies in patients supporting the therapeutic potential of t-PA, cloning and expression of recombinant t-PA providing sufficient amounts for large scale clinical use, and demonstration of its therapeutic benefit in large multicenter clinical trials, mainly in patients with acute myocardial infarction (AMI), but also in patients with massive pulmonary embolism, ischemic stroke, deep vein thrombosis and peripheral arterial occlusion. Genetically modified variants of t-PA have been developed for bolus administration in patients with AMI.
 ...
PMID:Tissue-type plasminogen activator: a historical perspective and personal account. 1510 5

Thrombotic occlusive diseases are manifested in several disorders that have significant morbidity and mortality, including acute myocardial infarction, pulmonary embolism, deep venous thrombosis, and cerebrovascular accidents. This review summarizes the recently published literature covering thrombolytic therapies in these diseases, with particular attention to comparisons between the fibrin-specific tissue plasminogen activators (alteplase, reteplase, and tenecteplase) and the nonfibrin-specific activators (streptokinase or urokinase plasminogen activator). These agents act to convert plasminogen to plasmin, which in turn cleaves fibrin as part of the lysis process. Fibrin-specific activators were anticipated to be more efficacious and safer than nonspecific agents in thrombolytic occlusive diseases because of their pathophysiologically restricted mechanism of action. However, the fibrin-specific activators also lyse physiological hemostatic plugs, which can result in costly adverse events. Efficacy of fibrin-specific tissue plasminogen activators has been shown to be generally equivalent, with similar mortality rates compared with nonspecific agents; however, fibrin-specific agents may be associated with an increased incidence of intracerebral hemorrhage and with increased costs. Therefore, it appears that given equivalent efficacy, nonfibrin-specific activators, such as streptokinase or urokinase, may be a safer choice in many thrombotic situations.
 ...
PMID:Thrombolytic therapies: the current state of affairs. 1582 70

Thrombolytic drugs play a crucial role in the management of patients with acute myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial thrombosis, acute thrombosis of retinal vessel, extensive coronary emboli, and peripheral vascular thromboembolism. Recognition of the importance of fibrinolytic system in thrombus resolution has resulted in the development of different fibrinolytic agents. Now a days several newer plasminogen activators with different pharmacokinetic and pharmacodynamic properties have been developed to treat thrombotic disease, which are fibrin specific with prolonged half-life and can be administered as a single bolus.
 ...
PMID:Plasminogen activators: a comparison. 1627 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>