Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between factor VIII (AHF) procoagulant activity and factor VIII-related antigen were examined in patients with disseminated intravascular coagulation (DIC), pulmonary embolism (PE), and coronary artery disease with or without myocardial infarction (MI). It was found that 13 of 13 patients with DIC, 17 of 17 patients with PE, and 10 of 12 patients with MI possessed a significantly elevated factor VIII-related antigen to factor VIII activity ratio (VIII-ratio). The VIII-ratio returned to normal in each of 2 patients with DIC and 1 paitent with PE after treatment with heparin, heparin and alpha-amino-caproic acid, and heparin and coumadin respectively. In contrast, the VIII-ratio was slightly elevated only in 1 of 15 patients with coronary artery insufficiency without MI. In in vitro studies, after treatment of plasma with thrombin or plasmin, factor VIII activity was lost, whereas the amount of factor VIII-related antigen remained the same or was even increased when measured by agarose quantitative immunoelectrophoresis. These observations have led us to conclude that an elevated VIII-ratio is a very sensitive indicator of intravascular coagulation.
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PMID:In vivo and in vitro effects of thrombin and plasmin on human factor VIII (AHF). 13 71

This review deals with aspects of fibrinolysis in which significant developments have taken place in the last few years. The structural changes of plasminogen during its activation are now identified precisely; the recent description of a thrombotic tendency in a kindred characterized by a defect of this protein emphasizes its important role in the homeostatic balance. Several activators of plasminogen are now identified; some of them, such as tissue and vascular activators, appear to have an important role in physiology and pathology. The recent characterizations of the alpha 2-antiplasmin and of antiactivators have widened our understanding of the inhibitors of fibrinolysis: a defect of the plasmin inhibitor seems to be associated with an haemorrhagic tendency, whereas high antiactivator levels were encountered in thrombotic conditions. The clinical use of fibrinolytic agents appears to be promising in conditions such as recurrent deep vein thrombosis and in the post-phlebitic syndrome. Thrombolytic therapy with urokinase or streptokinase appears to have elective indications in patients with acute deep vein thrombosis and massive life-threatening pulmonary embolism.
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PMID:Progress in fibrinolysis. 16 15

The defibrinating agent ancrod has had limited clinical trial, but appears to give no advantages over heparin. Intravenous infusion of dextran, a glucose polymer, has been shown to have an antithrombotic effect in many experimental models of thrombosis. However, the evidence that dextran is a clinically valuable antithrombotic drug is conflicting. A number of controlled randomized studies have shown that dextran can prevent postoperative venous thromboembolism when a large volume of dextran 40 or 70 was infused rapidly during and after surgery. However, blood volume expansion during dextran treatment prohibits its use in patients with reduced cardiac reserve, and infrequent though sometimes severe, allergic reactions have been reported. Evidence that dextran is of value for the treatment of venous or arterial thromboembolism comes from uncontrolled studies and is not convincing. Many compounds have been shown to inhibit platelet function in vitro but only five of these drugs have been extensively evaluated as prophylactic or therapeutic antithrombotic agents in man. These are aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine and clofibrate. They have been evaluated mainly in patients with cerebral vascular disorders, coronary artery disease, peripheral artery ischaemia, venous thromboembolism, prosthetic heart valves, and in patients with arteriovenous shunts. The evaluation of the clinical effect of the platelet function suppressing drugs is in its early stages, but they appear to differ from each other in the spectrum of their clinical effectiveness, and they may be more effective in arterial than in venous thromboembolic disorders. Their role in the management of cerebral vascular disease and coronary artery disease is still uncertain, and should be clarified by the results of a number of multi-centre, prospective, randomized studies which are currently in progress. Three types of thrombolytic drugs have been evaluated clinically; the plasminogen activators streptokinase and urokinase, proteolytic enzymes such as plasmin, and agents which increase the level of endogenous plasminogen activator (e.g. anabolic steroids). Of these, the plasminogen activators now have a definite place in clinical practice. The plasminogen activators accelerate the lysis of recent venous thrombi and pulmonary emboli, and of arterial thrombi or emboli. Thrombolytic therapy with these agents should be considered particularly in patients with recent major pulmonary embolism, as lysis of recent emboli is rapid and substantial. It should also be considered in patients with recent extensive venous thrombosis, because total lysis of venous thrombi has been reported to result in long-term preservation of valve function, and is likely to prevent postphlebitic syndrome, though this has not been proven. However, plasminogen activator therapy carries a higher risk of bleeding than heparin treatment...
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PMID:Antithrombotic drugs: part II. 78 6

We observed the changes of molecular markers for hemostatic activation in a patient with acute pulmonary embolism treated with 2 x 10(7) unit tissue plasminogen activator (t-PA). Blood samples were obtained before, just after, at 30 min, 1, 2, 6, and 24 hours after the infusion. Molecular markers included thrombin-antithrombin III complex (TAT), plasminogen-alpha 2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). Marked elevation of TAT was observed from immediately after the t-PA infusion to 6 hours after, although it had been observed for only 1 hour in our previous report on the cases of acute myocardial infarction. PIC level was significantly increased during t-PA infusion but returned to almost baseline value 6 hours after the end of t-PA infusion. This finding was almost the same as the one previously reported concerning acute myocardial infarction cases. TM level increased throughout the evaluation, and remained so, even on the 7th day after t-PA infusion. Our present data revealed a clear difference between the reactive TAT increases after t-PA therapy in acute myocardial infarction cases and in acute pulmonary embolism cases. Our present data also revealed a prolonged elevation of TM during the acute period of pulmonary embolism. It is therefore necessary to keep an eye on the changes of molecular markers for hemostatic activation after t-PA therapy in acute pulmonary embolism.
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PMID:[The changes in molecular markers for hemostatic activation after t-PA therapy in case of pulmonary embolism]. 131 73

The plasminogen-plasmin enzyme system and its therapeutic manipulation provide the substrate for an assessment of the clinical use of thrombolytic agents. Proven effective in acute MI and its complications, such agents have other potential applications--e.g., in stroke or pulmonary embolism--and are being investigated in those contexts.
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PMID:Thrombolytic therapy: a state of the art review. 152 55

Disseminated intravascular coagulation (DIC) can be defined as evidence of activation of the coagulation mechanism resulting in proteolysis of fibrinogen by thrombin and plasmin and an acute thrombocytopenia. The association of pulmonary embolism (PE) with DIC has recently been reported but in reviewing recent textbooks of hematology, there is no mention of PE as a cause of DIC. Clinicians need to be made aware of this association since it affects the patient who is thought to be autoanticoagulated as well as the patient who has DIC of unknown cause. PE needs to be included in the differential diagnosis of an autoanticoagulated state and in DIC of unknown etiology. In both instances the recommended treatment is full-dose intravenous heparin therapy.
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PMID:Massive pulmonary embolism presenting as disseminated intravascular coagulation. 160 44

Conventional thrombolytic therapy with streptokinase (SK) at the standard dose (loading dose, 250,000 IU; maintenance dose, 100,000 IU/h) after recent surgery may provoke a tendency towards severe bleeding secondary to plasminaemia associated with clotting disorders. In contrast, ultrahigh-dose SK therapy regimen (loading dose, 4 million IU; maintenance dose, 1-2 million IU/h) can minimize the risk of bleeding. Since the circulating plasminogen (Plg) can immediately bind to SK to form the so-called SK-Plg activator complex, free plasminogen is no longer available for conversion to systemic plasmin. In a pilot study, greater than 30 patients presenting with acute respiratory distress syndrome (ARDS) received ultrahigh-dose SK therapy following recent surgery. Although the period between surgery and thrombolysis was 2.5 days on average, no major haemorrhages occurred. In addition, a surprisingly high survival of 50% was reported. Although the efficacy of the ultrahigh-dose SK regimen in ARDS has not been definitively confirmed, this regimen is well accepted for the treatment of severe pulmonary embolism after surgery. Another promising indication for the use of this therapy is catheter-induced thrombosis of the major central veins. Additional, albeit rare, situations in which this treatment can be used include intrabronchial administration of thrombolytic agents after blood aspiration or their selective intravenous use following severe venous thrombosis in high-risk patients. This paper demonstrates the feasibility of thrombolytic therapy in these indications and discusses the benefit/risk ratio of the different agents tested.
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PMID:[Fibrinolytic therapy in surgically treated intensive care patients]. 181 12

A congenitally abnormal fibrinogen (Vlissingen) was isolated from the blood of a young woman suffering from massive pulmonary embolism. Fibrinogen Vlissingen showed an abnormal clotting time with both thrombin and Reptilase. The release of the fibrino-peptides A and B by thrombin was normal, but fibrin polymerization was impaired both in the presence and absence of Ca2+ ions. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis performed according to Laemmli the gamma-chain of fibrinogen Vlissingen showed two bands, one normal and one having an apparently lower molecular mass of about 1,500 daltons. The previously described protective effect of Ca2+ ions on plasmin degradation of the carboxyl terminus of the gamma-chain of normal fibrinogen was only partially detectable in fibrinogen Vlissingen. In addition the binding of Ca2+ ions was decreased. Fibrinogen Vlissingen bound 2.4 Ca2+ ions per fibrinogen molecule at pH 7.4, whereas normal fibrinogen bound 3.1 Ca2+ ions. At pH 5.8 fibrinogen Vlissingen bound 1.1 Ca2+ ions, whereas normal fibrinogen bound 2.0 Ca2+ ions per molecule fibrinogen in the D-domains, again indicating a structural change in the carboxyl terminus of fibrinogen. The structural defect was determined by sequence analysis of DNA amplified by use of the polymerase chain reaction. Exons VIII, IX, and X of the gamma-chain gene were amplified and the DNA sequence of the amplified fragments was determined. A 6-base deletion was found in 50% of the fragments corresponding to exon VIII, indicating that the patient was heterozygous for the mutation. This deletion codes for amino acids Asn-319 and Asp-320 in the normal fibrinogen gamma-chain. The data indicate that Asn-319 and Asp-320 are crucial for maintaining the integrity of the carboxyl-terminal polymerization sites, the protective effect of Ca2+ ions on plasmin degradation of the carboxyl terminus of the gamma-chain, and the calcium binding domain at the carboxyl terminus of fibrinogen.
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PMID:A congenitally abnormal fibrinogen (Vlissingen) with a 6-base deletion in the gamma-chain gene, causing defective calcium binding and impaired fibrin polymerization. 207 11

Tissue-type plasminogen activator (t-PA) is a serine protease that converts a zymogen plasminogen into an active serine protease, namely, plasmin. Plasmin is the proteolytic enzyme that degrades fibrin. In the absence of fibrin, e.g., in circulating plasma, t-PA activates plasminogen at a very slow rate. However, when fibrin is present, this activity is enhanced two to three orders of magnitude. As a consequence of these kinetic characteristics, plasmin is predominantly generated on the fibrin surface. This in turn results in a relative sparing of circulating fibrinogen and other plasma proteins to plasmin--mediated degradation. Following the demonstration of the potential of natural t-PA as a thrombolytic agent, an intensive effort was launched to enhance its production by recombinant DNA technology. The pharmacological action and the clinical efficacy of t-PA has been tested by several Authors in the treatment of acute myocardial infarction (AMI), and more recently, of pulmonary embolism, a condition for which this drug seems to be very promising: from this point of view this short article provides evidence that the various thrombolytic agents are of equal ability in mediating the rapid lysis of a coronary thrombus after i.v. administration when given appropriately and at the proper time; clinical experience provides little support for the contention of the superiority of t-PA over other thrombolytic agents, particularly for coronary thrombolysis. We are waiting for the results that will come from the GISSI-2 study, that is comparing streptokinase (SK) vs. t-PA in AMI's patients.
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PMID:[Tissue-type plasminogen activator]. 211 66

Tissue-type plasminogen activator (t-PA), an important component of the fibrinolytic system, is now available as a biotechnologically manufactured recombinant protein for therapeutic use. It has proved highly effective in the clinical therapy of acute thromboembolic diseases such as myocardial infarction and pulmonary embolism. t-PA activates plasminogen to plasmin, which subsequently dissolves the fibrin network of a blood clot. This activation by t-PA occurs selectively on the clot surface, with negligible systemic side effects. The half-life of t-PA in vivo is in the order of minutes due to rapid hepatic elimination. t-PA is a glycoprotein with serine protease activity and consists of a polypeptide chain with 527 amino acids. Recently, intensive research efforts have been devoted to modification of the molecular structure of t-PA, with the objective of further increasing fibrin specificity and catalytic activity, or reducing the rate of elimination. As a result, considerable insights into structure-function relationships within the t-PA molecule have been gained, but as yet no clinically utilizable variant has been constructed which is in all respects superior to naturally occurring t-PA.
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PMID:Properties of molecular variants of tissue-type plasminogen activator. 250 92


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