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)

Five criteria for poor response to a 20 min venous occlusion test were applied to 58 patients 3 months or more after acute deep vein thrombosis (DVT). The criteria were arbitrarily defined as the last 5 percentiles of response distributions in an age- and sex-matched healthy control group of 51 subjects. The criteria were: 1. euglobulin clot lysis time after venous occlusion greater than or equal to 140 min; 2. t-PA activity after venous occlusion less than or equal to 0.04 IU/ml; 3. increase in t-PA antigen above resting value less than or equal to 2-fold; 4. ratio between t-PA antigen increase and resting PAI activity less than or equal to 0.5 ng/IU; 5. PAI activity after venous occlusion greater than or equal to 6 IU/ml. The last criterion of poor response was the only one that was significantly more frequently reached by patients than by controls: 28% (p less than 0.005) of all DVT patients and 35% (p less than 0.005) of the subgroup with idiopathic DVT (N = 34) were found to be poor responders. The percentage of poor responders according to the other four criteria was 7-11% in all patients and 9-15% in the subgroup with idiopathic DVT and thus was not significantly higher than in controls (5% by definition). It was concluded that residual PAI activity after venous occlusion might be a useful criterion for prospective studies on recurrence of DVT.
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PMID:Poor fibrinolytic response to venous occlusion by different criteria in patients with deep vein thrombosis. 178 30

Coagulation and fibrinolytic studies have been performed in patients who were undergoing major gynaecological surgery and randomised to either fixed minidose warfarin (1 mg daily) or matched placebo. With warfarin, a prolongation of the prothrombin time was observed on day 2 which persisted for at least 5 days and was greater than with placebo. The maximal postoperative mean INR was, however, only 1.2 which is considerably less than the target value for prophylaxis of deep vein thrombosis with full dose warfarin. The warfarin group showed two unexpected findings: significantly elevated fibrin specific degradation products throughout the postoperative period compared with placebo and absence of the expected rise of PAI, the major fibrinolytic inhibitor, on the first day after surgery. Levels of fibrinogen degradation products and F1 + 2 prothrombin fragments rose significantly and progressively in both groups in the postoperative period. With placebo, F1 + 2 showed an apparent higher percentage increase on each post-operative day but the differences between the groups were not significant. Increased fibrinolysis may be one of the mechanisms for the protective action of minidose warfarin in prophylaxis of DVT after major surgery.
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PMID:Effects of fixed minidose warfarin on coagulation and fibrinolysis following major gynaecological surgery. 208 36

Defibrotide, a deoxypolyribonuclide, has been found to modulate endothelial cell function causing increase in t-PA and decrease in PAI levels and also increase in PGI2 production. In addition, it increases platelet c-AMP levels and decreases MDA and TXB2 formation in human. Defibrotide inhibits platelet aggregate formation in vitro experiments as well as end-to-end anostomosis in rats. So, defibrotide inhibits the activation of platelets. Besides an increase of protein C and S levels a synergic action of heparin was observed in animal experiments. A strong antithrombotic effect has been observed in animal models. The drug has a beneficial effect in the cases of DVT, POVD, stroke and thromboembolism. Through its action we may say that the drug acts in a novel fashion in contrast to the other drugs used in this area. Defibrotide is a single-stranded polydeoxyribonucleotide obtained from deoxyribonucleic acid of mammalian lungs by controlled depolimerization. Since 1981 in our laboratory and in the clinical department we have been investigating a newly developed agent defibrotide in vitro experiments, animal experiments, and also its clinical pharmacology and clinical application. Some of our findings are already published and compared with literature (40, 43, 46). Because of the limited space we are not going to review the literature in detail but we are going to summarize our observations on this compound in the following order. I--in vitro experiments, II--Animal experiments, III--clinical pharmacology in human.
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PMID:The pharmacology and clinical pharmacology of defibrotide: a new profibrinolytic, antithrombotic and anti-platelet substance. 210 24

Using affinity chromatography on lysine Sepharose 4B, a fast-acting tissue plasminogen activator inhibitor (t-PAI) was partially purified from t-PAI-rich plasma from patients with recurrent DVT. Its inhibition of tissue plasminogen activator (t-PA) was demonstrated in functional assays and its reaction with 125I-t-PA was analyzed by autoradiography following SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis). When the t-PAI was mixed with an equimolar concentration of t-PA at 37 degrees C, the half-life of free one-chain and two-chain 125I-t-PA was 1.8 and 0.8 min, respectively. The rate of complex formation between 125I-t-PA and t-PAI was similar both in patient plasma, pregnancy plasma and platelet lysates made from platelet-rich normal, patient and pregnancy plasma. The molecular weights of the complexes between t-PA and the inhibitors in patient plasma and in the different platelet lysates were identical, while that of the inhibitor complex formed in pregnancy plasma was found slightly higher by SDS-PAGE indicating that the pregnancy plasma t-PAI differs from the fast-acting t-PAI found in plasma from thrombotic patients and in platelet lysates.
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PMID:Plasminogen activator inhibitors in plasma and platelets from patients with recurrent venous thrombosis and pregnant women. 308 15

An enzyme-linked immunosorbent assay for plasminogen activator inhibitor-1 (PAI-1) in biologic fluids was developed on the basis of two murine monoclonal antibodies raised against PAI-1 purified from HT-1080 fibrosarcoma cells. The lower limit of sensitivity of the assay in plasma is 2 ng/mL. The assay is 12 times less sensitive toward the PAI-1/human tissue-type plasminogen activator (t-PA) complex as compared with free PAI-1. The intraassay, interassay, and interdilution coefficients of variation are 5.2%, 8.0%, and 7.1%, respectively. The level of PAI-1 in platelet-poor plasma of healthy subjects is 18 +/- 10 ng/mL (mean +/- SD, n = 45). In platelet-rich plasma after freezing and thawing, 92% of PAI-1 antigen is released from platelets, whereas only 8% is found in the corresponding platelet-poor plasma. In platelet-poor plasma from healthy subjects, a linear correlation (r = 0.80) was found between PAI activity and PAI-1 antigen. In plasma approximately two thirds of the PAI-1 antigen was functionally active, whereas only 5% of the PAI-1 antigen released from platelets was active. During pregnancy a progressive increase of PAI-1 antigen levels up to three- to sixfold the control value was observed. In plasma of patients with recurrent deep vein thrombosis, PAI-1 levels were 44 +/- 20 ng/mL (mean +/- SD, n = 7), during a clinically silent phase. Four of these patients had a level above 38 ng/mL (mean +/- 2 SD of normal). The present assay, based on stable and reproducible reagents, allows the specific determination of PAI-1 antigen in biologic fluids. It may facilitate interlaboratory comparisons and be useful for further investigations of the role of PAI-1 in clinical conditions associated with impaired fibrinolysis and/or a tendency to thrombosis and investigations of the role of PAI-1 in platelets.
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PMID:Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. 325 45

Twenty-five patients with phlebographically confirmed deep vein thrombosis of the lower limb were treated with intravenous infusions of low molecular weight heparin for 7 to 29 days. The mean dosage was 15.2 +/- 3.0 Uanti-Xa (equivalent 7.6 +/- 1.5 U-aPTT). Phlebograms were taken before, during and after the treatment with low molecular weight heparin and evaluated using the score system of Marder. Nearly complete recanalization of the occluded veins was found in six (24%) patients, improvement of the Marder score of 60 to 90% was found in four patients and of 30 to 60% in seven patients, while eight patients remained unchanged. With an average dose of 15.2 I.U./kg/h the heptest was prolonged to 70 to 120 seconds while the aPTT-level did not significantly increase. tPA-antigen-levels increased significantly in most of the patients after the third day of treatment, while PAI-activity remained unchanged. A positive conclusion between the decrease of the Marder score and the duration of treatment was found. Thus the low molecular weight heparin used in this investigation proved to be effective and safe in treating deep vein thrombosis.
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PMID:Regression of deep vein thrombosis by i.v.-administration of a low molecular weight heparin--results of a pilot study. 801 18

The alterations of the laboratory assays described for heparin monitoring in low molecular weight and unfractionated heparin prophylaxis groups did not correlate with the clinical outcome. Current laboratory techniques failed to detect an increased need for a higher dose of unfractionated or low molecular weight heparin to prevent DVT in these high-risk patients. The parameters commonly associated with thrombosis, that is, decreases in protein C and AT III were correlated with an increased incidence of DVT, but there was no difference in the assay values between the low molecular weight heparin and unfractionated heparin groups. Fibrinolysis activation is known to be associated with surgery; however, our data suggest an additional activation due to low molecular weight heparin compared with the unfractionated heparin group. Most interestingly, elevated PAI levels appear to correlate with thrombosis.
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PMID:Postoperative monitoring of low molecular weight heparin prophylaxis in high-risk patients. 839 35

Hip arthroplasty is associated with a high frequency of postoperative solitary proximal deep vein thrombosis which seems most frequently observed when bone cement is used for prosthesis fixation. Eighteen pigs underwent hemiarthroplasty, eight with cement-fixed prostheses and eight with non-cement prosthesis installation. Levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA) activity and plasminogen activator inhibitor 1 (PAI-1) activity were determined in femoral vein blood from both limbs during and after surgery. On the operated side, TAT increased during bone traumatization followed by a substantial rise in t-PA activity and a gradual decline in PAI-1 activity. This indicates a local per- and post-operative sequential activation of coagulation and fibrinolysis followed by a fibrinolytic shutdown, all reflected in femoral vein blood on the operated side. In the animals receiving noncemented hip prostheses, the same pattern of activation of coagulation and fibrinolysis occurred on the operated side. This was, however, less marked than with the cement-fixed prostheses. Postoperative scanning electron microscopic (SEM) examination of the femoral veins showed thrombi on the operated side in 62% of the animals in the cement group and 25% in the non-cement group. In an additional study with eight animals undergoing cement-anchored hip prosthesis operations the levels of TAT, t-PA and PAI-I were analysed in femoral vein blood, mixed venous blood and arterial blood. Significantly higher levels were found in femoral vein blood compared with mixed venous blood while no significant change was found in arterial blood compared with mixed venous blood. The hyperthermia induced by curing bone cement was effectively conducted by the implanted prosthesis and did not seem to exert major influence on the activation of coagulation. Extreme rotation of the limbs during surgery did not in itself induce visible vein wall damage as judged by SEM. These studies indicate that traumatization of bone marrow during hip surgery induce a marked local activation of coagulation and a high incidence of deep vein thrombosis in proximal veins, in particular if bone cement is used for prosthesis fixation.
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PMID:The role of bone traumatization in the initiation of proximal deep vein thrombosis during cemented hip replacement surgery in pigs. 882 20

Plasma plasminogen activator inhibitor-1 (PAI-1) level was observed to be associated with sequence variations at the PAI-1 locus. Therefore, PAI-1 gene promoter was screened for possibly new polymorphisms and to investigate the contribution of these sequence variations to PAI-1 levels in patients with deep vein thrombosis (DVT). DNA was isolated from blood of 83 consecutive unrelated patients (42 +/- 11 years old) and from 50 apparently healthy subjects of similar age and gender distribution. Six fragments covering DNA sequence- 1523 base pairs (bp) upstream from the start of PAI-1 gene transcription to +90 bp in the first exon, were amplified by polymerase chain reaction and analyzed by single-strand conformation polymorphisms. Two polymorphisms were found: a previously described 4G/5G deletion/insertion polymorphism -675bp upstream from the start of transcription and a novel G/A single base substitution polymorphism further upstream at -844 bp. The two polymorphisms were in strong linkage disequilibrium. Significant differences between patients and controls were observed neither for the frequencies of the 4G/5G alleles (0.60/0.40 and 0.59/0.41, respectively) nor for the frequencies of the G/A alleles (0.33/0.67 and 0.41/0.59, respectively). The distribution of both polymorphisms was similar in idiopathic and secondary DVT as well as in first and recurrent DVT. In patients association between the 4G/5G genotypes and PAI activity was observed, with the highest values in the 4G/4G genotype (13.3 U/mL), median values in the 4G/5G genotype (9.8 U/mL) and the lowest values in the 5G/5G genotype (2.0 U/mL). Despite the lack of association between the G/A genotypes and plasma PAI-1 levels, electrophoretic mobility shift assay showed specific binding of a nuclear protein from human vascular endothelial cells extracts to both the G and the A variant, suggesting functional importance of this novel G/A polymorphism in regulating the expression of PAI-1 gene.
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PMID:A novel G/A and the 4G/5G polymorphism within the promoter of the plasminogen activator inhibitor-1 gene in patients with deep vein thrombosis. 898 64

The role of hereditary antithrombotic protein defects in juvenile deep vein thrombosis (DVT) was evaluated. Fifty six young patients (age <45 yr) with doppler-proven DVT were investigated for the presence of resistance to activated protein C (APC-R), lupus anticoagulant (LA), anticardiolipin antibodies and deficiencies of protein C, protein S, ATIII activities. Fifty nine normal healthy individuals served as controls. APC-R was observed to be the commonest defect underlying the Indian DVT as seen in 39.2% of patients followed by elevated ACA (5.3%), PAI (2.8%), presence of LA (2.8%) and reduced ATIII levels (2.8%). None of the subjects had protein C or S deficiency. APC-R was associated with ATIII deficiency in one case, and elevated ACA in two cases. In two subjects, APC-R was associated with elevated PAI levels. Patients with more than one prothrombotic factor had a higher prevalence of pulmonary thromboembolism, suggesting that the thrombogenic potential of APC-R is enhanced by the presence of coexisting hereditary or acquired prothrombotic defect.
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PMID:Pathogenetic factors underlying juvenile deep vein thrombosis (DVT) in Indians. 1041 51


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