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)

Hypercoagulable states due either to inherited or acquired thrombotic risk factors are only present in approximately half of cases of DVT, but the causes in the other half, remain unknown. The importance of biological risk factors such as hyperlipidemia, hypofibrinolysis and hemorheological alterations in the pathogenesis of DVT has not been well established. In order to ascertain whether the above mentioned biological factors are associated with DVT and could constitute independent risk factors, we carried out a case-control study in 109 first DVT patients in whom inherited or acquired thrombophilic risk factors had been ruled out and 121 healthy controls age (42+/-15 years) and sex matched. From all the biological variables analyzed (cholesterol, triglycerides, glucose, fibrinogen, erythrocyte aggregation, hematocrit, plasma viscosity and PAI-1) only fibrinogen concentration reached a statistically significant difference on the comparison of means (290+/-73 mg/dl in cases vs 268+/-58 mg/dl in controls, p<0.05). After this continuous variables were dichotomized according to our reference values, the percentage of cases with cholesterolemia >220 mg/dl, hematocrit >45% and fibrinogen >300 mg/dl was higher in cases than in controls: 38% vs 22%; p<0.01; 43% vs 27%; p<0.05; 36% vs 23%; p<0.05, respectively. The percentage of cases with PAI-1 values >30 ng/ml, 37% vs 25% was borderline significant; p=0.055. Multivariate logistic regression analysis showed that cholesterolemia >220 mg/dl and fibrinogen >300 mg/dl constitute independent predictors of venous thrombotic risk. The adjusted OR's were 2.03 (95% CI; 1.12-3.70) for cholesterolemia and 1.94 (95% CI; 1.07-3.55) for fibrinogen. When these two variables combined DVT risk rose about fourfold (3.96; p<0.05). Our results suggest that hypercholesterolemia and hyperfibrinogenemia should be added to the list of known DVT risk factors and we recommend adopting measures to decrease these variables in the population with a high risk of DVT.
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PMID:Biological risk factors for deep vein trombosis. 1190 70

Although the common 4G/5G polymorphism in the promoter of the PAI-1 gene was suggested to be a risk factor for some of the thrombotic disorders, its significance in the development of thrombosis is still controversial. This study presents the data on a total of 357 patients with different types of thrombosis and 281 unrelated healthy controls. It was found that the 4G/4G genotype is associated with a higher risk of thrombosis (OR, 1.7; 95% CI, 1.1-2.5). Patients were divided into five distinct groups according to the site of thrombosis. Both 4G/4G and 4G/5G genotypes were associated with a higher risk of thrombosis development in a group of 69 patients with internal organ thrombosis (OR, 6.35; 95% CI, 2.5-16.1 and OR, 4.85; 95% CI, 2.0-12.1, respectively). Interestingly, this association was even stronger in a subgroup of 33 patients with portal vein thrombosis (PVT) and 4G/4G and 4G/5G genotypes conferred more than 10- and 6-fold increases in the risk of developing PVT (95% CI: 2.3-47.1 and 1.4-28.8), respectively. No statistically significant association was found between 4G/4G genotype and the groups of deep vein thrombosis (126 patients), cerebral thrombosis (80 patients), retinal thrombosis (72 patients), and purpura fulminans (16 patients). Factor V Leiden or prothrombin G20210A mutations did not emerge as additional risk factors for thrombosis in any of the groups studied. To conclude, this study suggests that there may be an association between 4G/4G and 4G/5G genotypes and the thrombosis in vessels of internal organs especially in the portal veins.
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PMID:PAI-1 gene 4G/5G genotype: A risk factor for thrombosis in vessels of internal organs. 1235 6

External pneumatic compression (EPC) devices prevent lower extremity deep venous thrombosis (DVT) by reducing stasis. There is a widely held belief that they also enhance endogenous fibrinolysis; however, recent studies of tissue plasminogen activator (the primary activator of fibrinolysis) and plasminogen activator inhibitor-1 (the primary inhibitor of fibrinolysis) failed to confirm this. The hypothesis of this study was that EPC devices increase the level of urokinase plasminogen activator (uPA), a second activator of fibrinolysis. This was a prospective trial in which 44 subjects who underwent major abdominal surgery were randomized to receive unfractionated heparin injections, thigh-length sequential EPC devices, or both for DVT prophylaxis. Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or discharge. Venous blood samples were collected from an antecubital vein for measurement of systemic uPA levels and from the common femoral vein for measurement of regional uPA levels. Samples were collected the day before surgery, after induction of anesthesia but before surgical incision, and on postoperative days 1, 3, and 5. uPA levels (ng/mL) were measured with an enzyme-linked immunoassay. Baseline uPA levels (0.41 to 0.56 ng/mL; P >.05, analysis of variance with repeated measures) were similar among the three groups. uPA levels did not change after surgery in systemic or regional blood samples in any group. There were no significant differences in systemic or regional uPA levels in the groups treated with EPC devices relative to those treated with heparin at any time point (P >.05, analysis of variance with repeated measures). Enhancement of fibrinolysis with EPC devices remains unproven; the findings reported here suggest that effective DVT prophylaxis can only be assured when the devices are used in a manner that reduces venous stasis.
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PMID:External pneumatic compression does not increase urokinase plasminogen activator after abdominal surgery. 1242 1

The most important complication of arthroscopy of the knee is DVT. We studied 53 patients who undergoing arthroscopy with artificial ischemia of lower limb. We examined some biochemics and haematological dates, for example lactate, APTT, INR, PAI-1 etc. In our collection we did not find any case of thromboembolic disease. It seems, that arthroscopy operation with artificial ischemia of lower limb do not increase the risks of DVT. We means, that especially in cases with longer tourniquet time (more than 30 min) is better, when we give some type of Heparin (best is LMWH) as prevention of DVT, because in laboratory results we found significant increase of PAI-1. It is possible, that it can be caused by the rising thrombus.
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PMID:[Metabolic changes caused by artificial ischemia in knee arthroscopy]. 1268 45

The possible existence of distinctive, vascular bed specific alterations of coagulation and fibrinolytic parameters associated with three different types of thrombosis was investigated in young women (n = 68, <45 years at onset of the event) following myocardial infarction (MI) (n = 22), lacunar cerebral infarction (LACI) (n = 16), idiopathic deep vein thrombosis (VT) (n = 14) and venous thrombosis due to oral contraceptive use (n = 16) in the stable period after the acute thrombotic event. Coagulation and fibrinolytic parameters, as well as classical metabolic variables, were measured and compared with 52 age-matched, healthy controls. In MI women we observed elevated tissue type plasminogen activator (t-PA) antigen levels, which correlated significantly with parameters of the plurimetabolic syndrome. In LACI women we found elevated fibrinogen, which correlated with D-dimer, systolic blood pressure, smoking, and sedimentation rate. Prolonged euglobulin clot lysis time, elevated t-PA antigen, PAI-1 antigen and activity, which all correlated with parameters of the plurimetabolic syndrome, were found in women with idiopathic VT, who were also clearly obese but not in women in whom oral contraceptives were the triggering factor for VT. Our results showed not parallel, but different profiles of alterations in fibrinolytic and coagulation parameters in line with the prediction of a vascular bed specific thrombosis process.
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PMID:Vascular bed specific alterations in coagulation and fibrinolytic parameters in young women following myocardial infarction, lacunar cerebral infarction and deep vein thrombosis. 1462 51

Genetic and acquired factors may influence phenotypic expression of inherited thrombophilia. Hypofibrinolysis due to excess PAI-1 can be found in patients with deep vein thrombosis (DVT) and 4G/5G polymorphism of the PAI-1 gene may modulate the inhibitor's synthesis. In 149 patients with inherited thrombophilia, the possible thrombotic contribution of both 4G/5G polymorphism and PAI-1 plasma levels was evaluated. Sixty-seven patients with idiopathic DVT and 98 normal subjects were also studied. By comparison with controls, a significantly higher prevalence of 4G/4G genotype was seen in idiopathic DVT and in thrombophilia patients, although in this latter group the difference only remained significant in cases symptomatic for thrombosis (p = 0.01). The 4G/4G genotype was associated with a greater risk of thrombosis both in symptomatic thrombophilia patients (OR 2.85, 95% CI 1.26-6.46) and in idiopathic DVT patients (OR 3.1, 95% CI 1.26-7.59). The greater frequency of 4G allele in symptomatic thrombophilia patients with respect to controls was statistically significant (p = 0.04). Compared to healthy subjects, PAI-1:Ag levels were higher in symptomatic thrombophilia patients and related to the 4G/5G polymorphism, with significantly higher values in the 4G/4G carriers. In conclusion, PAI-1 4G/5G polymorphism may influence PAI-1 expression and thrombotic risk in patients with inherited thrombophilia.
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PMID:The PAI-1 gene 4G/5G polymorphism and deep vein thrombosis in patients with inherited thrombophilia. 1465 39

A kindred was examined in which the 48-year-old white female proband with three deep venous thrombosis-pulmonary emboli events had four thrombophilic and one hypofibrinolytic mutations, and in which her 14-year-old asymptomatic daughter had four thrombophilic mutations. The proband was heterozygous for the G1691A factor V Leiden, G20210A prothrombin, and platelet glycoprotein IIIa PL A1/A2 mutations, had high factor VIII (221%), and was homozygous for the 4G4G plasminogen activator inhibitor-1 gene mutation, with high plasminogen activator inhibitor activity (23.7 U/mL). Her 14-year-old daughter was homozygous for the G1691A factor V Leiden and platelet glycoprotein IIb-IIIa PL A2/A2 mutations, compound heterozygous for the C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) mutations, and heterozygous for the G20210A prothrombin mutation, a combination with an estimated likelihood of 1.6 x 10(-7). In 247 white healthy controls, there was no V Leiden homozygosity and no V Leiden-prothrombin gene compound heterozygosity. Heterozygosity for the V Leiden and prothrombin gene mutations was 3.2% and 4.1%, respectively. Homozygosity for the platelet glycoprotein IIb-IIIa PL A2A2, PAI-1 gene 4G4G, and C677T MTHFR mutations was 3.2%, 22.7%, and 12%, respectively. The proband will receive anticoagulation therapy for life. Beyond aspirin, avoidance of exogenous estrogens, and enoxaparin prophylaxis during pregnancy, it is not known whether the proband's daughter should have lifelong anticoagulation therapy, or only after her first thrombotic event.
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PMID:Ramifications of four concurrent thrombophilic mutations and one hypofibrinolytic mutation. 1549 23

"Evidence-based" recommendations for warfarin prescription in patients with history of ischemic stroke limit its use to prevention of stroke due to atrial fibrillation. Warfarin is also prescribed by the authors to prevent thrombosis in stroke patients with thrombophilia and potential cardiac or arterial source for thromboembolism. These potential conditions, in the face of thrombophilia, include, but may not be limited to, dilated cardiomyopathy, decreased left ventricular function, atrial septal aneurysm with or without patent foramen ovale (PFO), PFO with evidence of pelvic or lower extremity deep venous thrombosis or with clear thrombophilia, spontaneous echocardiographic contrast, intracardiac or intra-arterial thrombus, intra-aortic arch thrombus, high degree of stenosis of large- and medium-sized cerebrovascular arteries, and arterial dissection. Commonly diagnosed thrombophilic states in our population currently include protein S or C deficiency, antiphospholipid antibodies, and less commonly ATIII deficiency, factor V Leiden mutation, G20210A PT mutation, and plasminogen activator inhibitor-1 mutation. Thrombophilic states often occur in combination. The occurrence of combined arterial, cardiac, and thrombophilic sources of thromboembolism poignantly describes the complexity of causation of ischemic stroke in any one patient. Our practice of treating the complex interaction of thromboembolic sources is based on scientific evidence, which is not arbitrarily limited to probability-based statistics. Warfarin is well known in the clinical setting to interact with many different contextual factors of the individual patient, making its dosing and response unique to that patient. We have shown why the indications for warfarin use and its dosing cannot be directly extrapolated to the individual patient from the results of large, double-blind, randomized trials. In practice, the unique patient and his or her context must be considered by the expert physician who makes the therapeutic decision. The context includes, but is not limited to, known pathologies that contribute to thrombus formation according to the accepted pathophysiologic model of thrombosis based on Virchow's triad of altered flow, endothelium, and blood components.
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PMID:Fuzzy logic and continuous cellular automata in warfarin dosing of stroke patients. 1600 52

Tissue factor (TF) mRNA levels in leukocyte and TF antigen in plasma were examined in patients with deep vein thrombosis (DVT). Although TF mRNA levels in leukocytes were higher in patients with DVT than in healthy volunteers, they were lower in patients with DVT than in those with solid cancer and those with disseminated intravascular coagulation (DIC). On the other hand, the plasma levels of TF antigens were markedly high in patients with DVT/pulmonary embolism (PE). Analysis of the role of underlying disease of DVT showed no significant difference in TF mRNA levels and TF antigens among patients with solid cancer, post-surgical, other diseases and those free of underlying diseases. In patients with VTE, plasma levels of D-dimer, soluble fibrin, GE-XDP and plasminogen activator inhibitor-1 did not correlate with TF mRNA or TF antigen. In analysis of 18 patients with PE with and without DVT, TF mRNA levels in leukocytes correlated with the plasma levels of D-dimer. These findings suggest that TF in leukocytes is more likely to be involved in the development of thrombosis in PE than DVT.
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PMID:Elevated levels of leukocyte tissue factor mRNA in patients with venous thromboembolism. 1603 15

We present the case of a 64 year-old female patient, with a clearly positive family history of venous thromboembolism (VTE), multiple VTE episodes (massive pulmonary embolism, ovarian venous plexus thrombosis, deep venous thrombosis with submassive pulmonary embolism and second deep venous thrombosis) and myocardial infarction. Laboratory tests revealed the resistance to the activated protein C, elevated FVIII and PAI-1. The patient was found to be a heterozygous carrier of FV Leiden, MTHFR C677T and PAI-1 4G/5G mutations. She was diagnosed with essential thrombocythemia at the age of 60. The thirty-three-year follow-up of our patient and detection of recurrent thrombotic episodes in the light of multiple coagulation defects with proved acquired risk factors, contributes to the risk stratification in the group of patients with very high risk. In case of our patient, we stress inadequacy of widely-accepted standard prevention measures. In our opinion, patients with very high risk require additional mechanic and specific medicament methods of VTE prevention.
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PMID:Combined thrombophilic risk factors and essential thrombocythemia in patient with recurrent venous thromboembolic episodes-thirty-three-year follow-up. 1605 98


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