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)

Intermittent pneumatic compression (IPC) devices are an effective prophylaxis against lower extremity deep vein thrombosis. Their antithrombotic effect has been attributed to a reduction in venous stasis and enhanced fibrinolysis. The initiating mechanism for blood coagulation is the tissue factor (TF) dependent pathway, which is inhibited by tissue factor pathway inhibitor (TFPI). We have investigated the effect of IPC on the TF pathway in 6 normal subjects and 6 patients with postthrombotic venous disease undergoing IPC for 120 minutes; all subjects were studied with each of 5 IPC devices. In normal subjects and patients, plasma factor VIIa (FVIIa) activity (the activated form of factor VII [FVII]) declined from mean values ranging 51 to 65 and 50 to 53 mU/mL before IPC with different devices to 10 to 13 and 20 to 22 mU/mL at 180 minutes, respectively (P<0.001 for all groups). FVII antigen levels were unchanged. Plasma TFPI (P<0.001) rose from mean baseline values ranging 69 to 79 and 57 to 61 ng/mL to 76 to 123 and 71 to 79 ng/mL at 180 minutes in normal subjects and patients, respectively (P<0. 001 for all groups). Plasma prothrombin fragment F1.2 levels showed minimal changes. There was an inverse relationship between TFPI and FVIIa in normal subjects (r=-0.31, P=0.001) and patients (r=-0.37, P<0.001). IPC results in an increase in plasma TFPI and decline in FVIIa. Inhibition of TF pathway, the initiating mechanism of blood coagulation, is a possible mechanism for the antithrombotic effect of IPC.
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PMID:Inhibition of tissue factor pathway during intermittent pneumatic compression: A possible mechanism for antithrombotic effect. 1055 31

For somewhat more than a decade low molecular weight heparins have dominated in the pharmacological prevention of postoperative venous thromboembolism. At present there are some new methods of potential interest both as prophylactic substances but also to better understand the pathophysiology of deep vein thrombosis. These are inhibition of factor VII a/tissue factor complex (NAP, Nematode Anticoagulant Protein), inhibition of activated factor X (the synthetic pentasaccharide fondaparinux) and thrombin inhibition (melagatran and its oral prodrug ximelagatran). They have been shown to be effective in high risk orthopaedic surgery. They have to show their place in the prophylactic arsenal in comparison with low molecular weight heparins (effect, safety, mode of administration, cost-effectiveness).
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PMID:[Prophylaxis of postoperative thromboembolism. New alternatives to low-molecular-weight heparin]. 1217 May 16

Because of its high negative predictive value, D-Dimer is an important parameter in the exclusion of deep vein thrombosis (DVT) but it produces a high number of false-positive results. We therefore evaluated different blood parameters in 74 consecutive patients with suspected DVT, whose final diagnosis was based on the results of Duplex ultrasound or venography. DVT was diagnosed in 52.7%. While D-Dimer, thrombin-antithrombin complexes, prothrombin fragment 1+2, von-Willebrand factor and thrombus precursor protein were significantly increased in patients with DVT, there was no influence concerning endogenous thrombin potential and activated factor VII. There was no significant correlation between the thrombus extension or the duration of symptoms with any of these parameters. D-Dimer showed the best sensitivity (94.9%) to specificity (45.7%) ratio and neither the sole nor the additional evaluation of any other investigated parameter increased its diagnostic performance. We, therefore, conclude that the determination of D-Dimer remains the 'gold standard' in the laboratory testing of patients with suspected DVT.
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PMID:Thrombus precursor protein, endogenous thrombin potential, von-Willebrand factor and activated factor VII in suspected deep vein thrombosis: is there a place for new parameters? 1249 87

Two new classes of anticoagulants in development at the present time [anti-factor Xa and anti-factor IIa (direct antithrombin) agents] should change our future strategies for prevention and treatment of venous thromboembolic events. Among the anti-factor Xa, the pentasaccharides are initiating their clinical use. Fondaparinux, the synthetic form of the natural pentasaccharide is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. A modified form (idraparinux) whose pharmacokinetics allows one administration only once a week should have the same type of efficacy. Among direct antithrombin agents, hirudin and derivatives have been developed in the past decade burt are not routinely used. Synthetic direct antithrombins allowing oral route are currently developed: Exanta with the most advanced development, is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. It could allow (if confirmed by clinical trials) a complete oral treatment of deep vein thrombosis without any biological monitoring. Exanta is also active in the prevention of arterial thromboembolic events on atrial fibrillation. Other molecular forms of synthetic per os direct antithrombin are also in development. But molecules aimed at other targets are also tested: the most advanced are those antagonizing the initial phase of tissue factor activation of factor VII but other strategies are being tested such as stimulation of fibrinolysis.
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PMID:[New and future antithrombotic agents in thrombo-embolic venous disease]. 1267 26

Two new classes of anticoagulants are actually developed which would change in the near future our strategies for the prevention and the treatment of venous thromboembolic events. These two classes are the anti-factor Xa and anti-factor IIa (direct antithrombin) agents. Among the anti factor Xa, the pentasaccharides are initiating their clinical use. Fondaparinux is a synthetic form of the natural pentasaccharide, its pharmacokinetics allows one s.c. administration/24 hours. It is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. A modified form (idraparinux) whose pharmacokinetics allows one administration only once a week should have the same type of efficacy. Among direct antithrombin agents, hirudin and derivatives have been developed in the past decade with a limited use due to several drawback. More recently synthetic direct antithrombins modified to allow oral route have been developed, the most advanced in development, melagatran, is active in the prevention and treatment of venous thromboembolic and coronary thrombotic events. It could allow (if confirmed by clinical trials) a complete oral treatment of deep vein thrombosis without any biological monitoring. Melagatran is also active in the prevention of arterial thromboembolic events on atrial fibrillation. But other molecular forms of synthetic orally active direct antithrombin are also in development. Besides these important changes in our therapeutics which should appear in a near future, molecules aimed at other target are also tested: the most advanced are those antagonizing the initial phase of tissue factor activation of factor VII but other strategies are being tested such as stimulation of fibrinolysis. These new drugs at our disposal to treat venous thromboembolism should modify completely our handling of the patients. But additionally the numerous clinical trials necessary to prove the efficacy of the drugs, modify our understanding in the implication of the coagulation and in the physiopathogeny of thrombotic events.
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PMID:[Treatment and prevention of venous thromboembolic events: present and future antithrombotic agents]. 1455 56

Excessive coagulation and impaired fibrinolysis lead to many hemostatic disorders, which enhance the risk of development of life-threatening cardiovascular diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism, belonging to the most important factors influencing morbidity and mortality in civilized societies. The adverse events induced by currently used drugs, the need for regular monitoring of coagulation parameters, inconvenient, in some cases, route of administration stimulate further search for novel, effective and safe methods of therapies of these disorders. In this paper, we describe those new agents which are now under experimental and clinical study, such us prostanoids, nitroaspirin, GP IIb/IIIa receptor antagonists, thienopyridine derivatives, collagen-GPVI and von Willebrand factor-GPIb-IX contact blockers, direct thrombin inhibitors, inhibitors of thrombin-platelet interactions, factor VII inhibitors and tissue factor-factor VII contact blockers. Based on the available literature, we discuss the possible role of these agents in the future prevention and treatment of thromboembolic diseases.
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PMID:Progress in pharmacotherapy of thrombosis. 1458 10

A 30-year-old female with severe factor XI deficiency of 0-2% acquired factor XI inhibitor following many infusions for fresh frozen plasma (FFP) for surgical procedures starting at 4 years of age. Seven months before this inhibitor was diagnosed, surgery was complicated by prolonged bleeding resistant to FFP, requiring epsilon aminocaproic acid (EACA) and surgical packing. The inhibitor was measured at 2.2 Bethesda units, 7 months since the last FFP. The inhibitor was confirmed as specific anti-XI and anti-XIa binding by patient's IgG to immobilized factor XI and factor XIa from whole plasma and purified IgG. For repair of a painful anterior cruciate ligament (ACL) defect she was given recombinant factor VIIa (rVIIa) at 90 mug kg(-1), starting one-half hour preoperatively and continued every 2 h for 8 h when haemostasis was complete. Thereafter the rVIIa was given every 3 h for two doses, and then every 4 h for four doses at which time she was discharged on EACA which was continued for 6 days. There was excellent haemostasis during and following the surgery. There was no evidence of consumptive coagulopathy, with no change in the fibrinogen, platelet count, or D-D dimer; and no increase of platelet factor 4, beta-thromboglobulin, or prothrombin fragment F 1.2. The thrombin-antithrombin complex increased over baseline after 24 h. There was no postoperative deep vein thrombosis or pulmonary embolus. In this patient with a factor XI inhibitor, the recombinant factor VIIa was effective and safe, ensuring adequate haemostasis with no thrombotic complications. This product which was designed for patients with inhibitors to factor VIII or factor IX, and factor VII deficiency, has now been given successfully to four patients with factor XI inhibitors.
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PMID:Treatment of factor XI inhibitor using recombinant activated factor VIIa. 1566 Sep 84

A thorough review of the literature and of personal files has allowed the gathering of 81 patients with rare congenital bleeding disorders and thrombotic phenomena. Sixteen of these patients had congenital afibrinogenemia, eight involved factor V deficiency, 20 factor VII defects, 33 factor XI deficiencies and only one, a factor XIII defect. Altogether 42 patients showed arterial thrombosis (myocardial infarction [MI] in 28 cases; ischemic stroke in 4; arterial occlusion in 8; 2 patients with disseminated intravascular coagulation (DIC)). Ages varied between 13 and 74. Twenty-two patients were males and 16 females. In four cases, sex was not reported. There were three fatalities: two after a MI and one because of heart failure. With regard to venous thrombosis: 9 patients had pulmonary embolism, 15 patients had deep vein thrombosis, 9 patients had both pulmonary embolism and deep vein thrombosis; 1 patient had superficial vein thrombosis, whereas, 5 cases had an unusual site venous thrombosis (two portal systems, two cerebral sinuses, one inferior vena cava) for a total of 39 cases. Age varied between 3 and 86. In this case, 20 patients were males and 17 were females. In two cases, sex was not reported. There were three fatalities: two because of pulmonary embolism and one because of inferior vena cava thrombosis. The fact that thrombosis has never been described in patients with factor II or factor X seems to underscore the central antithrombotic role that these two factors have in the coagulation system.
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PMID:Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review. 1683 33

A 37-year-old woman affected by renal insufficiency was submitted to renal transplantation from cadaver donor. After a few days she had a severe and life-threatening hemorrhage at the surgical site and a deep venous thrombosis at her lower right limb. Since anticoagulant therapy was contraindicated, a filter was inserted in the inferior vena cava. After several red blood cell, fresh plasma and platelet transfusions, and after repeated unsuccessful surgical procedures, a single dose of 70 microg/kg of body weight of recombinant activated factor VII (rFVIIa) was administered as last resource. The drug was successful in obtaining the complete and rapid resolution of the hemorrhagic episode. Despite the patient had two factors which could have favoured a thrombotic complication, e.g. deep venous thrombosis and caval filter, administration of rFVIIa did not worsen the underlying thrombotic process. rFVIIa is a new hemostatic agent that was initially used in hemophiliac patients. Later it has been successfully used in nonhemophiliac patients to treat different inherited or acquired coagulation disorders. A potential thrombogenic effect of rFVIIa was hypothesized on the basis of some clinical case reports but large controlled trials do not exist. In this case report the use of rFVIIa was successful and safe despite the concomitant presence of several thrombogenic factors.
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PMID:Use of recombinant activated factor VII (rFVIIa-NovoSeven) in the treatment of uncontrolled postsurgical hemorrhage in a patient with deep venous thrombosis and caval filter. A case report. 1686 86

Measurements of hemostatic variables were performed prior to and up to the fifth day following general surgery in patients of Arab origin (N = 53). There was a significant postoperative elevation in the levels of plasma fibrinogen, clotting factors VIII and reduction of factor VII, ATIII, plasminogen, packed cell volume and platelet count. No significant changes were noted in PT, PTT, TT, RT, alpha-2-antiplasmin and factor X. Platelet aggregation responses to ADP, adrenaline, collagen, arachidonic acid and ristocetin was likewise unaffected by surgery. It was concluded that although the changes in plasmatic coagulation parameters are similar to that reported in Caucasians, lack of evidence of enhanced aggregation following surgery may explain the presumed low incidence of deep vein thrombosis in Arabs.
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PMID:Hemostatic changes following surgery. 1758 46


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