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

Plasminogen activator inhibitor (PAI-1), a member of the serine protein family, is the most active in vivo inhibitor of fibrinolysis induced by plasminogen, tissue plasminogen activator (tPA), and urokinase type plasminogen activator (uPA). While the association between elevated PAI-1 and thrombogenesis has been well studied for several disease processes, including coronary disease, postoperative deep vein thrombosis (DVT), myocardial infarction, malignancy, and diabetes, few studies have concentrated on the correlation between elevated PAI-1 levels and thrombogenesis in patients with myeloproliferative disorders. Essential thrombocythemia (ET), a chronic myeloproliferative disorder, characterized by the overproduction of poorly functioning platelets, is associated with both thrombotic and hemorrhagic life-threatening complications. Although the events resulting in thrombogenesis in such patients may be multifactorial in nature, an association between elevated PAI-1 levels and thrombus formation has been proposed. Herein we present a patient diagnosed with ET complicated by multiple episodes of arterial thrombosis. Elevations in PAI-1 levels were documented repeatedly. The role of elevated PAI-1 when associated with other disease processes is also discussed.
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PMID:Clinical implications of elevated PAI-1 revisited: multiple arterial thrombosis in a patient with essential thrombocythemia and elevated plasminogen activator inhibitor-1 (PAI-1) levels: a case report and review of the literature. 1043 40

We present the case of a man bedridden by deep venous thrombosis who was given intraclot instillations of recombinant tissue plasminogen activator with remarkable improvement. Although such aggressive treatment may be justified in severe cases, the role for thrombolytic agents for less symptomatic deep venous thrombosis is undefined. We discuss the question of when thrombolytic therapy should be considered. However, proper clinical trials are needed before firm recommendations can be made.
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PMID:Thrombolytic therapy for deep venous thrombosis? 1059 39

The antithrombotic activity of dermatan sulfate from avian crown with the mean molecular weight of 38000 was compared to those from bovine intestine with the mean molecular weight of 16000 in vivo and in vitro. In an in vitro test, bovine intestine dermatan sulfate exhibited stronger effects on stimulation of heparin cofactor II and activation of Glu-plasminogen by tissue plasminogen activator. In vivo, avian crown dermatan sulfate more effectively prevented the development of thrombus in a rat deep vein thrombosis model. The measurement of plasma levels of these two kinds of dermatan sulfate revealed that avian crown dermatan sulfate circulated in higher concentration and longer duration than bovine intestine dermatan sulfate after intravenous administration to rats.
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PMID:Antithrombotic activity of avian crown dermatan sulfate. 1063 69

The goals of treatment of acute iliofemoral DVT should be prevention of fatal PE, reduction of pain and swelling of the involved leg, trying to stop the development of phlegmasia cerulea dolens and venous gangrene, prevention of disabling PTS by early removal of the blood clot, avoiding proximal venous obstruction, preserving normal, functioning valves in the leg veins, and preventing reflux. The authors recommend an aggressive approach with rapid removal of the occluding thrombus in the leg veins extending up into the iliac veins in active patients with a short history of symptomatic DVT, usually less than 7 days. This approach is not justified in chronically ill, bedridden, high-risk, or aged patients, or those with serious intercurrent disease or limited life expectancy. In these patients, such interventions can only be indicated for limb salvage in phlegmasia cerulea dolens when conservative treatment does not prevent the development of an acute compartment syndrome with venous gangrene. The preferred means of accomplishing early and quick removal of the thrombus is CDITT. Most of the authors' positive experience with thrombolysis is based on the use of urokinase. The Food and Drug Administration (FDA) has put this drug on temporary hold for almost 1 year. The alternative drugs (e.g., tissue plasminogen activator [tPA]) have not been tested for CDITT of DVT, and tPA is not FDA-approved for this indication. When there are contraindications or failure of thrombolysis, TE with a temporary AVF is a valid alternative.
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PMID:Indications for surgical treatment of iliofemoral vein thrombosis. 1080 68

Patients in intensive care may be at high risk of in vivo platelet activation because comorbid conditions, such as infections, septicemia, shock, disseminated intravascular coagulation, and cancer represent procoagulant states. Hyperreactivity of platelets with or without a decline of cell count may result in thromboembolic complications potentially associated with the phenomenon of heparin-induced thrombocytopenia. We analyzed the data of 10 patients highly suspected of having heparin-induced thrombocytopenia during their intensive care treatment of 29 plus or minus 22 days. In seven patients, thrombocytopenia coincided with thromboembolic complications. Six patients had additionally undergone fibrinolytic therapy before starting activated partial thromboplastin time-adapted alternative anticoagulation with r-hirudin. In three patients, the platelet count decreased without a clinical manifestation, of heparin-induced thrombocytopenia. R-Hirudin treatment monitored by activated partial thromboplastin time and prothrombin time (PT) was effective and safe. The target value for activated partial thromboplastin time was a twofold prolongation. In four of five patients with deep venous thrombosis, a partial recanalization of the lower extremity could be achieved. Three patients with pulmonary embolism associated with deep venous thrombosis in two cases and in one additional case with an acute myocardial infarction did clinically profit from fibrinolysis with recombinant tissue plasminogen activator (rtPA) and r-hirudin treatment. Two lethal events probably caused by the underlying multimorbidity could not be prevented. No recurrence of thrombosis occurred, and there were no severe bleeding complications attributed to r-hirudin treatment. Platelet counts were significantly reduced on day 9.4 plus or minus 6.4 of heparin administration in all cases (>50% decrease related to the initial values) from 224,000 plus or minus 126,000/microL to 96,000 plus or minus 61,000/microL, and increased during rhirudin treatment to mean values of 224,000 plus or minus 126,000/microL. The heparin-induced platelet activation assay (HIPAA) assay was positive in 8/10 cases, whereas the PF4 enzyme-linked immunosorbent assay showed a positive result in four of eight analyzed cases. In four cases, the assays were concordantly positive. The PF4 enzyme-linked immunosorbent assay was not performed in two cases.
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PMID:Heparin-induced thrombocytopenia: a critical risk/benefit analysis of patients in intensive care treated with R-hirudin. 1089 75

The strong fibrin affinity of recombinant tissue plasminogen activator (rt-PA) theoretically obviates continuous infusion or replacement of t-PA after direct intrathrombic injection. This hypothesis led the authors to evaluate single daily catheter-directed injection of rt-PA as a thrombolytic treatment for acute deep vein thrombosis of the lower extremity. Once-daily injection of rt-PA was performed in large thrombosed veins (popliteal or larger) with use of pulse-spray catheters and in small thrombosed veins in patients' calves with use of 3-4-F coaxial catheters. Patients received only full systemic anticoagulation on his/her patient care unit. This dosing regimen has been tested in 10 patients (12 legs) with a maximum dose of 50 mg per leg per day. Extensive thrombolysis was achieved in nine patients and partial thrombolysis was achieved in one patient, at an average total dose of 106 mg of rt-PA per leg. Minor bleeding was seen in three patients and no transfusions were needed. Our technique and the rationale for this pilot study is the focus of this article.
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PMID:Daily catheter-directed single dosing of t-PA in treatment of acute deep venous thrombosis of the lower extremity. 1126 90

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.
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PMID:Improving natural principles with genetic engineering: TNK-tissue plasminogen activator. 1145 85

Deep venous thrombosis is a possible complication of indwelling central venous catheters (CVC), with an incidence as high as 61%. We report a case of successful thrombolysis of a CVC-related right atrial thrombus in a pediatric cancer patient with recombinant human tissue plasminogen activator (0.1 mg/kg per h for 12 h) and heparin (10 IU/kg per h for 24 h) administered for 6 days. Daily echocardiographic examination showed progressive lysis of the thrombus. The thrombolytic treatment was associated with mild oozing from the venipuncture sites, but no major bleeding was noted; moreover, thrombin, thromboplastin time and fibrinogen were normal or only minimally altered. Anticoagulant therapy, with or without CVC removal, is the treatment of choice for uncomplicated CVC-related thrombosis. Fibrinolytic therapy may be indicated in some cases at risk of pulmonary embolism or to avoid open heart surgery. Recombinant human tissue plasminogen activator is increasingly used for thrombolytic treatment of organ and limb thrombosis, but experience with it in the pediatric hematology-oncology setting is still limited. This report showed that administering recombinant human tissue plasminogen activator in a pediatric cancer patient prior to hematopoietic stem cell transplantation was effective and safe under strict biochemical and instrumental monitoring. Further studies are needed to determine the best antithrombotic treatment for CVC-related thrombosis, and also the dosage of the medication selected and the duration of treatment.
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PMID:Successful treatment of a catheter-related right atrial thrombosis with recombinant tissue plasminogen activator and heparin. 1190 91

Plasminogen activators (PA) are unique agents that are currently applied as thrombolytic therapy to achieve rapid vascular reperfusion. Regimens of PA plus anticoagulants and antiplatelet drugs have attained a high degree of sophistication and predictable rates of positive clinical outcomes for acute myocardial infarction (MI), ischemic stroke, pulmonary embolism (PE), deep vein thrombosis (DVT), and thrombosed catheters. Included in the repertoire are newly approved mutants of tissue plasminogen activator (TPA), which have biochemical advantages that allow for bolus administration. Yet, despite tremendous effort devoted to enormous trials to establish the clinical efficacy of these agents in acute MI, mortality results are not superior to those with native TPA or streptokinase (SK). Furthermore, all PAs have the potential for hemorrhagic complication, most critically intracranial hemorrhage (ICH), occurring in 0.9% of patients treated with native or mutant TPA. It is possible that a limit of clinical effectiveness has been reached, beyond which more potent PAs do not achieve greater benefit without a serious increase in risk of bleeding. A breakthrough is possible, however, if the risk of ICH could be avoided. One solution is the application of the direct-acting thrombolytic enzyme, plasmin. While intravenous plasmin is not effective when administered systemically, regional infusion to a thrombus induces local thrombolysis. Unlike the PAs, plasmin treatment should not cause hemorrhage from vascular trauma sites, as it is neutralized by antiplasmin in the blood. Animal studies are fully consistent with this approach, which offers potential for achieving a truly regional thrombolytic treatment.
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PMID:Towards safer thrombolytic therapy. 1212 83

External pneumatic compression (EPC) devices prevent lower extremity deep venous thrombosis (DVT) by reducing stasis. There is a widely held belief that they also enhance endogenous fibrinolysis; however, recent studies of tissue plasminogen activator (the primary activator of fibrinolysis) and plasminogen activator inhibitor-1 (the primary inhibitor of fibrinolysis) failed to confirm this. The hypothesis of this study was that EPC devices increase the level of urokinase plasminogen activator (uPA), a second activator of fibrinolysis. This was a prospective trial in which 44 subjects who underwent major abdominal surgery were randomized to receive unfractionated heparin injections, thigh-length sequential EPC devices, or both for DVT prophylaxis. Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or discharge. Venous blood samples were collected from an antecubital vein for measurement of systemic uPA levels and from the common femoral vein for measurement of regional uPA levels. Samples were collected the day before surgery, after induction of anesthesia but before surgical incision, and on postoperative days 1, 3, and 5. uPA levels (ng/mL) were measured with an enzyme-linked immunoassay. Baseline uPA levels (0.41 to 0.56 ng/mL; P >.05, analysis of variance with repeated measures) were similar among the three groups. uPA levels did not change after surgery in systemic or regional blood samples in any group. There were no significant differences in systemic or regional uPA levels in the groups treated with EPC devices relative to those treated with heparin at any time point (P >.05, analysis of variance with repeated measures). Enhancement of fibrinolysis with EPC devices remains unproven; the findings reported here suggest that effective DVT prophylaxis can only be assured when the devices are used in a manner that reduces venous stasis.
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PMID:External pneumatic compression does not increase urokinase plasminogen activator after abdominal surgery. 1242 1


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