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)

Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.
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PMID:Age-related changes in factor VII proteolysis in vivo. 875 6

The diagnosis of thromboembolic diseases is still difficult to establish before the occurrence of the pathological event, although it is now known that they are the result of a progressive alteration of the cardiovascular system. Introduction of new diagnostic tools for the evaluation of the thromboresistance capacity of the body or for the measurement of molecular markers allows the testing of the body defenses against thrombosis which is becoming a routine clinical diagnosis. Antithrombin III (AT III), protein C, protein S, and parameters of fibrinolysis have been recognized to be very important anticoagulant proteins and regulators of thrombin formation and thrombus extension. Furthermore, a normal factor V is necessary for the normal function of the protein C pathway. The presence of a factor V mutation leads to the activated protein C resistance syndrome. However, the major incidence of thrombotic events concerns the overall population. It has been epidemiologically related to the existence of risk factors producing blood activation, which progressively saturates the body's thromboresistance. This period is clinically silent for a long time. The new molecular markers recently introduced can show the existence of a preclinical state of blood activation at the plasma level (fibrinopeptide A, thrombin-antithrombin complexes, modified antithrombin III, fragments 1 + 2 of prothrombin, D-dimer) or at the platelet level (B-thromboglobulin, platelet factor 4, and thrombospondin), and promising developments concern the endothelial level (soluble thrombomodulin). The most universally used blood activation test is the D-dimer assay. This analyte has become very popular in past years for its high sensitivity, its long half-life, and its easy detection directly on citrated plasma. Its negative predictive value (in deep venous thrombosis or pulmonary embolism) as well as its use for monitoring of thrombotic risk in the post-operative period have been well documented clinically. New investigations are initiated to find analytes reflecting endothelial damage, an early platelet activation, or the involvement of blood cells (mainly monocytes and neutrophils) in abnormal processes. It also becomes possible to evaluate directly pathological causes inducing blood activation, such as the presence of antiphospholipid antibodies or other autoimmune antibodies.
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PMID:Thromboembolic diseases: biochemical mechanisms and new possibilities of biological diagnosis. 880 28

In a multicentric study the influence of heparinase (Hepzyme) was evaluated on activated partial thromboplastin time, thrombin clotting time and prothrombin time using the recombinant human tissue factor and synthetic phospholipid (phosphatidylcholine and phosphatidyl-serine reagent). Hepzyme itself does not have any influence on normal coagulation values of activated partial thromboplastin time (aPTT) and prothrombin time (PT) assays whereas thrombin clotting time was prolonged by 10% (n = 60). In patients treated with unfractionated heparin for recent deep vein thrombosis (n = 47), plasma levels of aPTT, PT and thrombin clotting time (TCT) returned to the normal range in 100%, 97% and 91% after treatment with heparinase, respectively. Plasma samples of patients on coumarin were spiked with 2IU heparin/ml (n = 40) and were treated with heparinase. aPTT returned to baseline levels in 97.5%, PT in 99% and TCT in 69% of the samples. Plasma samples of patients receiving both heparin and coumarin were treated with heparinase (n = 18). aPTT and TCT values were shortened substantially and displayed the prolongation due to the effect of oral anticoagulants. PT values in these patients were also shortened. Freezing of plasma samples after treatment with heparinase resulted in a prolongation of the coagulation times in 15% of PT, 7% of aPTT and not of TCT values. The results show that treatment of plasma samples with heparinase abolishes the effect of unfractionated and low molecular weight heparin in vitro and ex vivo in patients during simultaneous treatment with oral anticoagulants. The use of heparinase may be of significance in patients with concomitant treatment of heparin and oral anticoagulants.
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PMID:Multicentric evaluation of heparinase on aPTT, thrombin clotting time and a new PT reagent based on recombinant human tissue factor. 883 97

The aim of the study was to compare the efficacy and safety of once-daily subcutaneous injection of dalteparin, a low molecular weight heparin, with that of intravenous unfractionated heparin in the treatment of deep venous thrombosis (DVT). Patients were included if they had deep venous thrombosis distal to inguinal ligament and were randomised either before, if it was considered necessary, or after phlebographic verification of the diagnosis. There was no pre-inclusion treatment with unfractionated heparin. One hundred and twenty patients received dalteparin, administered subcutaneously once-daily at a fixed dose of 200 IU anti-factor Xa/kg, and 133 patients received a continuous intravenous infusion of unfractionated heparin (UFH). Oral anticoagulation was started on the first or second day, and initial treatment with dalteparin or UFH discontinued when the prothrombin time was in the therapeutic range (2 < INR < 3) on two consecutive days. Control phlebograms were taken within 4 days, thereafter. There were no significant differences between the two initial treatment groups in improvements in Marder score. Two major bleeding events occurred in the UFH group versus none in the dalteparin group. One patient in each group experienced clinically significant pulmonary embolism. During a mean follow-up period of 6.9 +/- 1.5 months, recurrent DVT occurred in four patients in the dalteparin group and in two of the UFH group. These results confirm those of a previous study on dalteparin in the initial treatment of DVT, and suggest that dalteparin administered once-daily at a fixed dose of 200 UI/kg is as effective and well-tolerated as UFH in patients with DVT below the inguinal ligament. The present study also demonstrates that dalteparin can be started as soon as the diagnosis of DVT is suspected and without pre-treatment with UFH. Given that the administration of once-daily subcutaneous injections needs not require a patient to be hospitalised, studies to investigate the possibility of using dalteparin for the initial treatment of DVT in the outpatient setting are warranted.
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PMID:Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. 886 30

In a 6-month, randomized, double-blind study the effects of two combined oral contraceptives containing 150 micrograms desogestrel and either 20 or 30 micrograms ethinylestradiol on hemostatic parameters were investigated in 1633 healthy women. Compared with baseline, the 30 micrograms ethinylestradiol formulation increased prothrombin fragment 1 + 2 (+72.2%), D-dimer (+42.4%) and protein C activity (+6.1%), whereas antithrombin-III activity (-6.3%) and protein S activity (-19.7%) were decreased. The use of the 20 micrograms ethinylestradiol formulation was associated with the same pattern of changes, but with lower magnitude (F1+2 + 61.1%, D-dimer +36.0%, antithrombin III -5.3%, protein C +4.6% and protein S-16.0%). The changes from baseline were significantly smaller in the 20 micrograms ethinylestradiol group for D-dimer, antithrombin III and protein S than in the 30 micrograms ethinylestradiol group (p = 0.019, p = 0.038 and p = 0.001, respectively). One woman with a combined deficiency of proteins C and S developed deep venous thrombosis while using the 20 micrograms ethinylestradiol formulation. Use of both formulations was associated with a shift of the coagulation-fibrinolysis balance to an enhanced fibrin-generating and fibrin-degradating activity. The less-pronounced effect on hemostasis with the 20 micrograms ethinylestradiol preparation is reassuring with regard to thromboembolic risk in general. However, women with coagulation inhibitor deficiency should be advised not to use oral contraceptives.
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PMID:Ethinylestradiol 20 versus 30 micrograms combined with 150 micrograms desogestrel: a large comparative study of the effects of two low-dose oral contraceptives on the hemostatic system. 890 27

Eight patients with femoro-popliteal or sural DVT, confirmed by phlebography, were treated with intravenous Desmin (LMW-dermatan sulphate): on the first day, after an initial i.v. injection of 400 mg, all patients received an infusion of 800 mg in 500 ml of saline, during 24 hours; this infusion was repeated in each of the subsequent 9 days (global treatment period: 10 days). To monitor efficacy of the antithrombotic treatment a phlebography, with calculation of Marder score, was repeated at the end of treatment. Laboratory tests monitoring blood coagulation were carried out: aPTT, TT, PT. Factor Xa inhibition (by chronometric and chromogenic method), Stachrom DS, fibrinogen, prothrombin fragments F1 + 2 and TAT. Seven patients completed the ten-day treatment: 6 patients evidenced good improvement of the phlebographic patterns, 1 remained stationary and 1 patient was withdrawn due to adverse events. During the ten days treatment we did not observe any variation of blood coagulation tests. Desmin tolerability was good and no haemorrhagic episodes were registered. The collected results point to a good antithrombotic activity of the new LMW-dermatan sulphate, that deserves to be further evaluated with controlled investigations on larger number of patients.
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PMID:The treatment of deep vein thrombosis with continuous intravenous low-molecular-weight dermatan sulphate (Desmin). A pilot study. 898 60

This paper reports on the results of a Phase I, dose-finding study with a new low molecular mass heparin (LMMH) called RO-11. The study focused on pharmacokinetics, dose-effect relationship and on tolerability of three single subcutaneous (s.c.) doses within the therapeutical range. After the injection of 7,500, 9,000 and 12,500 anti-FXa i.u., the anti-FXa effect peaked between 3-6 h and showed a dose-dependent response. The absorption and elimination were first-order processes and the long half-life (> 5 h) kept constant after increasing doses. The compound was tolerated very well and no clinically relevant prolongation of APTT, prothrombin and thrombin clotting tests was observed. At the dose of 7,500 i.u., which corresponded to 110 anti-FXa i.u./Kg, RO-11 exerted anti-FXa effect for at least 18-20 h. We recommend using this dose in a single s.c. injection, to evaluate the efficacy and safety of RO-11 in the initial treatment of DVT or PE.
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PMID:Pharmacokinetics and tolerability of a new low molecular mass heparin (RO-11) in healthy volunteers--a dose-finding study within the therapeutical range. 903 63

An initial course of standard heparin (SH) or low-molecular-weight heparins (LMWH) is regarded as the treatment of choice for patients with deep venous thrombosis (DVT). LMWH have better bioavailability after subcutaneous administration, have a longer half-life, and show higher and more predictable anticoagulant activity. As a result they can be given subcutaneously and without laboratory control, using a dose that is determined by bodyweight. Because of these multiple advantages of LMWH they will replace SH in the future and subsequently home treatment with LMWH of selected patients seems feasible. The currently accepted approach is to start with SH or LMWH therapy combined with oral anticoagulant therapy. (OAT) at the time of diagnosis. The course of SH or LMWH should continue for at least 5 days, provided that international normalized ratio (INR) is in the therapeutic range on 2 consecutive days. OAT should be continued for at least 3 months to prolong the prothrombin time to an INR of 2-3. When oral anticoagulants are either contraindicated or inconvenient, SH or LMWH can be used at the middosing interval. The role of anti-platelet treatment is not yet established and should be compared with coumarin therapy in the future.
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PMID:New developments in the treatment of deep venous thrombosis. 903 42

Deep vein thrombosis (DVT) is a frequent event in patients with spinal cord injury, even with prophylactic anticoagulant therapy. Lower limb paralysis is a known major risk factor for venous thrombosis, supposedly due to the venostasis in relation with total immobility. The main goal of this study was to evaluate the endothelial response to anoxia to determine whether recovery of fibrinolytic potential occurs in patients subjected to forced bedrest because of a spinal cord injury and whether this recovery is related to the incidence and/or evolution of DVT. We evaluated vascular endothelium reactivity in the lower limbs no longer submitted to the hydrostatic pressure of the erected position in 15 patients with paraplegia or tetraplegia and in 10 normal volunteers after venous occlusion produced by the application of 10 cm Hg pressure to the lower limb for 15 min comparatively to the upper limb used as reference. Among the 15 patients, 10 whose spinal cord injury had occurred 1 to 6 months earlier were still receiving prophylactic anticoagulant therapy, whereas the five other patients were not receiving prophylactic anticoagulants because the injury dated back 6 months or more. After venostasis, tissue plasminogen activator (tPA) increased significantly in both patients and controls in the upper limb (tPA levels twofold and threefold respectively in controls and patients) but showed no significant changes in the lower limb; prolonged immobility did not allow recovery in the lower limbs of a level of fibrinolytic responsiveness identical to that in the upper limbs. The plasminogen activator inhibitor (PAI1) remained unchanged after anoxia, although wide interindividual variations were seen. Natural coagulation inhibitors and circulating blood stigmates of hypercoagulability were measured. None of the patients had abnormally low levels of coagulation inhibitors (ie, antithrombin III, protein C and protein S levels were normal). Seventy-five per cent of patients (prophylactically anticoagulated or not) had very high levels of fibrin degradation products (D. Dimer levels sevenfold to eightfold those of the controls), but all patients had normal levels of thrombin-antithrombin complexes and prothrombin fragments 1 + 2. The permanence of the thrombotic process characterized by an increase in D. Dimer levels without recovery of fibrinolytic potential suggests a proposal for the patients an indefinite antithrombotic treatment at curative doses.
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PMID:Endothelial fibrinolytic reactivity and the risk of deep venous thrombosis after spinal cord injury. 907 65

We have performed a prospective, randomized, controlled trial comparing continuous intravenous unfractionated heparin with twice-daily subcutaneous (s.c.) high-dose low-molecular-weight (LMW) heparin in the initial treatment of 50 patients with acute proximal deep vein thrombosis. In this article we analyze the relationship between the dosage of the heparins, the anticoagulant effects on aPTT, and thrombin and factor Xa inhibition to the improvement of the Marder score after a 10-day treatment period. Improvement of the Marder score was observed in about 70% of patients without regard to administration of unfractionated or LMW heparin. Patients in both treatment categories were divided into two groups, namely, those who showed an improvement of the Marder score and those who did not. In the group of patients with unfractionated heparin and regression of thrombus size the mean dosage was 33,000 U/day, whereas the mean dosage was 37,000 U/day in the patients with status idem of the Marder score after the 10-day treatment period. Thrombin clotting time values were in contrast to the dosage. Patients with regression of thrombosis showed higher thrombin clotting time values compared with those with status idem. These results were also seen with aPTT and the Heptest coagulation assay, but the differences between the two groups were less pronounced. No differences between these two groups of patients were seen or detected with the S2222 chromogenic anti-factor Xa method. Patients receiving 2 x 12,000 IU s.c./day LMW heparin did not show these differences, the dosage being adjusted by the anti-Xa levels, ranging from 0.6 to 1.0 U/mL 4 hours after the s.c. injection. The groups of patients categorized as to improvement or not of the Marder score did not show differences in the daily dose. The anti-Xa activity was higher in patients with regression of thrombosis compared with patients without regression. The other coagulation parameters did not show any relation to the clinical outcome of thrombus regression. The relationship between the change of the Marder score at day 10 and the anticoagulant effect on the different coagulation systems correlated weakly for patients receiving unfractionated heparin. The highest correlation was found for the improvement of Marder score and thrombin inhibition in the heparin group with r = 0.42. For LMW heparin no correlation could be detected. Heptest coagulation values were in the same range for patients receiving unfractionated and LMW heparin. In contrast to the chromogenic anti-Xa assay, aPTT, thrombin clotting time, and prothrombin time values differed substantially in the two treatment regimens. Treatment of recent deep vein thrombosis with unfractionated heparin profits from laboratory monitoring, whereas monitoring of the anticoagulant effect during the treatment with s.c. LMW heparin does not influence the outcome on thrombus regression.
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PMID:Dosage, anticoagulant, and antithrombotic effects of heparin and low-molecular-weight heparin in the treatment of deep vein thrombosis. 915 15


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