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)

Patients over 40 years of age who undergo elective orthopaedic surgery have a relatively high risk for developing post-surgical deep vein thrombosis (DVT). Prophylactic use of heparin or low molecular weight heparins can reduce the incidence of post-operative DVT by up to 80%. It is not known whether prophylaxis is achieved by inhibition of prothrombin activation or catalysis of thrombin inhibition in vivo. We determined the changes in concentrations of factor VII zymogen and thrombin-antithrombin III (the latter as an index of prothrombin activation) in the plasmas of 129 patients randomized to receive two daily subcutaneous injections of placebo or 30 mg of Enoxaparin after elective knee surgery. Enoxaparin reduced the frequency of post-surgical DVT by 70%. The concentration of factor VII zymogen had decreased by approximately 50% within 24 h after the knee surgery, followed by a gradual increase to near presurgical values. Additionally, post-Enoxaparin plasmas had statistically significant higher concentrations of factor VII zymogen than post-placebo plasmas. Post-Enoxaparin plasmas had significantly lower concentrations of endogenous thrombin-antithrombin III than comparable post-placebo plasmas. Finally, post-Enoxaparin plasmas inactivated exogenous factor Xa and thrombin more effectively than comparable post-placebo plasmas. As Enoxaparin moderated the generation of endogenous thrombin-antithrombin III after elective knee surgery, inhibition of prothrombin activation in vivo by Enoxaparin may be important for its prophylactic antithrombotic effect.
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PMID:The low molecular weight heparin Enoxaparin inhibits the consumption of factor VII and prothrombin activation in vivo associated with elective knee replacement surgery. 132 19

This study investigated whether the pre-surgical plasma levels of TAT and F1 + 2 of patients undergoing major surgery for localized tumours could identify patients at higher risk of thrombosis, and how heparin prophylaxis affected in vivo coagulation after cancer surgery. We measured the pre- and post-operative levels of TAT, F1 + 2, total factor VII (FVIIt) and zymogen FVII (FVIIz) in 117 cancer patients, with and without heparin prophylaxis. The end points of this study were DVT, initially detected by 125I-fibrinogen uptake test and confirmed by ascending venography. Pre-operative [TAT] and [F1 + 2] of the cancer patients were significantly higher than those of age-matched control subjects (n = 50) (P < 0.005 and P < 0.05, respectively); pre-operative [FVII] was not significantly different. One of the 83 patients receiving prophylaxis, and 8/34 not receiving prophylaxis developed post-operative DVT. Of the parameters evaluated, only the pre-operative [TAT] > 3.5 ng/ml identified patients at higher risk for post-operative DVT. Heparin reduced plasma TAT levels and FVII consumption following surgery, suggesting that heparin modulates coagulation associated with cancer surgery. The results of this study also suggest that the pre-operative [TAT] may identify patients with higher risk for post-operative DVT.
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PMID:Preliminary study to identify cancer patients at high risk of venous thrombosis following major surgery. 791 39

The plasma levels of coagulation factor VII and fibrinogen are well known risk factors for arterial thrombosis. We tested the hypothesis that this association also exists for venous thrombosis. Additionally, MspI and HaeIII polymorphisms in the factor VII and fibrinogen genes have recently been reported to be associated with the concentration of both proteins in the plasma. However, no conclusion could be drawn with respect to an increase or decrease in thrombosis risk. We undertook a population-based case-control study, in which 199 patients with a population-based case-control study, in which 199 patients with a first, objectively confirmed episode of deep vein thrombosis, aged less than 70, and without a known malignant disorder were compared to 199 age- and sex-matched healthy controls, to evaluate the clinical importance of these reported findings. For fibrinogen we found a positive level-related association between the plasma fibrinogen level and thrombotic risk. Subjects with a plasma fibrinogen greater than 5 g/l had an almost 4-fold increase of thrombosis risk. The frequencies of the different HaeIII genotypes were out of balance only for the thrombosis patients, with a deficit of the H1H2 genotype. Possession of an H1H2 genotype was associated with a 40% reduction in thrombosis risk. For factor VII, neither the plasma level nor the MspI genotypes were related to deep vein thrombosis, although possession of a M2 allele was clearly associated with significantly lower factor VII levels. The frequencies of the MspI-genotypes were the same for patients and control subjects and exhibited Hardy-Weinberg equilibrium. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factor VII and fibrinogen levels as risk factors for venous thrombosis. A case-control study of plasma levels and DNA polymorphisms--the Leiden Thrombophilia Study (LETS). 797 38

The activated protein C (APC)-resistance test is a simple and reliable method for detecting reduced sensitivity to the anticoagulant action of this protein. We investigated the sensitivity to APC in 180 Japanese controls and in 96 Japanese patients with venous and arterial thrombosis (28 with deep vein thrombosis; 13 with pulmonary thromboembolism; 41 with cerebral infarction; and 14 with coronary artery disease). All of the patient groups showed significantly reduced sensitivity to APC, reflected by the lower normalized APC-sensitivity ratio (n-APC-SR), as compared with healthy control. The APC-sensitivity ratio was negatively correlated with plasma activated factor VII levels. These results suggest that the low n-APC-SR is related to venous or arterial thrombotic disease. The APC resistance may serve as a potential marker for assessing the hypercoagulable state.
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PMID:Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state. 873 27

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 effect of incubation of plasma with lipoprotein lipase on factor VII coagulant (FVII:C) activity was examined in 40 patients, 22 male and 18 female, aged 28 to 77 years, with history of venographically proven deep venous thrombosis (DVT). While the mean (+/-SEM) FVII:C activity of the 40 patients was 100.9 +/- 4.1%, 19 patients had FVII:C activity less than 100%, 11 had 100 to 120% activity and 10 patients had greater than 120% FVII:C activity. The mean triglyceride level of all the patients was 84.0 +/- 6.5 mg/dl. The FVII:C activity correlated significantly with triglyceride (r = 0.36; n = 40; p = 0.021). There was about 30% average loss of FVII:C activity upon incubation of plasma with lipoprotein lipase. The mean activity loss increased from 23.8% to 31.5% and 42.6% in patients whose FVII:C activity levels were less than 100%, between 100 and 120% and more than 120% respectively, the variation in the means being statistically significant (p < 0.001). While according to current opinion, FVII:C activity represents the total FVII mass (FVII plus FVIIa) and activity state, the present findings demonstrate a lipid dependence of FVII:C activity, and raises the possibility of a therapeutic option of controlling FVII:C by controlling triglyceride levels.
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PMID:Triglyceride dependence of factor VII coagulant activity in deep venous thrombosis. 890 84

The authors report a study on the hemostatic status of a group of patients with deep venous thrombosis in order to highlight the possible pathogenetic responsibility of blood coagulative disorders in the genesis of thrombosis. The group consisted of 27 patients (14 males, 13 females, mean age 48 +/- 4 years) with deep venous thrombosis of the lower limbs (clinical symptoms were primary in 21 cases, secondary in 6 cases) diagnosed on the basis of clinical data and ultrasonographic instrumental findings. Fourteen normal subjects were also examined as a control group (12 males, 2 females, mean age 28 +/- 5 years). Venous blood was collected on fasting from patients and controls to examine the following parameters: fibrinogen (F), factor VII (F VII), antithrombin III (AT III), protein C (PC), protein S (PS) using coagulometric methods (IL), and tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), fibrinopeptide A (FPA), betathromboglobulin (BTG) and dimer-D (D-D) using ELISA methods (Boehringer). Patients with deep venous thrombosis showed a significant increase in F, FVII, tPA and D-D levels compared to controls, whereas a significant reduction was observed in PAI-1. Nonsignificant variations were found for AT III, PC, PS and BTG. In the light of these results the authors affirm that: high fibrinogen and factor VII levels are highly prognostic for thrombosis in patients with deep venous thrombosis; the importance of the lack of inhibitory factors (AT III, PC, PS) is confined to individual genetically predisposed cases; there is an efficacious hyperfibrinolytic reactive response to the presence of thrombus (increase in tPA and D-D, reduction of PAI-1).
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PMID:[Hemostatic status in subjects with deep venous thrombosis]. 905 19

Twenty four cases with rare coagulation disorders were diagnosed over a 4 year period. These included 8 patients with factor X deficiency, 7 with factor XIII deficiency, 4 each with fibrinogen and factor VII deficiency and 1 with factor V deficiency. All these patients had presented with bleeding manifestations. Two patients with factor X deficiency showed interesting clinical presentations, one patient had recurrent deep vein thrombosis and another patient had a pseudotumor of the thigh.
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PMID:Rare inherited coagulation disorders in India. 928 99

A high plasma concentration of factor VII procoagulant activity is considered an independent risk factor for coronary heart disease. Recently, two polymorphisms of factor VII gene (insertion of a decanucleotide at -323 [A2], and the variant Q353) have been associated with 20-25% lower levels of this protein in plasma. In this study, the prevalence of these two factor VII polymorphisms were evaluated in relation to the development of acute thromboembolic events. Thus, we conducted three case-control studies of patients diagnosed with acute coronary syndromes, acute cerebrovascular events and deep venous thrombosis (101, 104 and 97 cases, respectively). No significant differences were detected in the prevalence of these polymorphisms between patients and controls, suggesting that the A1/A2 or R/Q alleles do not play an important role in the development of thromboembolic episodes.
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PMID:Genetic polymorphisms of factor VII are not associated with arterial thrombosis. 966 10

The optimal procedure for withdrawal of warfarin in patients with deep vein thrombosis (DVT) is still not defined. Rebound thrombin generation, which occurs after the withdrawal of warfarin, has been said to be associated with early recurrence of DVT. The aim of this study was to compare two procedures for warfarin withdrawal after the first episode of DVT with respect to rebound thrombin generation. Forty-one consecutive patients were randomly assigned to abrupt withdrawal of warfarin (group A), or to an additional month of warfarin, at the fixed dose of 1.25 mg/day (group B). Plasma samples were withdrawn for the assay of prothrombin fragment F1+2 (F1+2), protein C, factor VII and International Normalized Ratio (INR), before any anticoagulant treatment (I), during initial heparin (II) and full dose warfarin (III), at the end of full dose warfarin (IV) and then 1 (V), 4 (VI), 5 (VII) and 9 (VIII) weeks after randomization. The mean duration of full-dose warfarin treatment, the mean warfarin dose and the mean INR during full-dose warfarin treatment were similar in the two groups. A decrease in F1+2 was observed during heparin and warfarin treatment (II, 1.7 nmol/ml; III, 1.0 nmol/ml; IV, 0.7 nmol/ml; versus I, 3.5 nmol/ml; P<0.01). After the withdrawal of warfarin, an increase in F1+2 was observed in both groups, but without significant statistical differences (group A: V, 1.2 nmol/ml; VI, 1.5 nmol/ml; VII, 1.6 nmol/ml; VIII, 1.1 nmol/ml; group B: V, 1.3 nmol/ml; IV, 1.5 nmol/ml; VII, 1.4 nmol/ml; VIII, 1.4 nmol/ml). No significant difference between the two groups was observed in the recovery of protein C and factor VII. Four patients experienced a recurrence of DVT, three in group B and one in group A. Our findings confirm that rebound thrombin generation occurs in patients with DVT after the withdrawal of warfarin. Rebound thrombin generation is not reduced by a low, fixed dose of warfarin.
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PMID:Withdrawal of warfarin after deep vein thrombosis: effects of a low fixed dose on rebound thrombin generation. 1045 21


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