Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evaluation of inherited thrombophilia in patients with venous thromboembolism includes testing for functional activity of antithrombin, protein C and protein S, and resistance to activated protein C (factor V Leiden), which can be assessed with plasma and DNA-based assays. The antiphospholipid syndrome is an acquired disorder related to the development of antibodies against phospholipid-protein complexes. Testing for the antiphospholipid syndrome includes measurement of antibodies to phospholipid-protein complexes by immunoassay or by detecting interference of anti-phospholipid antibodies in sensitive phospholipid-based assays. Other genetic risk factors have been listed, including a common polymorphism in prothrombin gene (3'-untranslated region) related to an increase of prothrombin level (> 115%) and a common polymorphism in the methylene tetrahydrofolate reductase (enzyme involved in homocysteine metabolism) gene related to a mild increase of homocysteine blood level. More recently high plasmatic levels of factor VIII (> 150%) or factor XI (> 120%), not related so far to a molecular defect, have been identified as risk factors for deep vein thrombosis. As a candidate gene, factor XIII gene polymorphisms are under investigation. Beside the acquired or genetic risk factors involved in thrombophilia, the gene-environment interactions are of importance in the onset of thrombosis.
 ...
PMID:[Laboratory testing for venous thromboembolism]. 1120 40

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are separate but related aspects of the same dynamic disease process known as venous thromboembolism (VTE). Recent community studies have shown that VTE is a major health issue for the developed world, with at least 201,000 new cases each year in the United States, comprising 107,000 with DVT and 94,000 with PE. A quarter of PE cases die within 7 days, some so rapidly that treatment or intervention is impossible. Despite the availability of heparin prophylaxis, the annual incidence of VTE has remained constant at 1 event per 1,000 person-years since 1979 but reaches 1 event per 100 person-years for the over-85-year-olds. The most important risk factors for VTE are hemostatic and environmental. The recent discoveries of factor V Leiden, prothrombin 20210A, and high concentrations of factor VIII have highlighted the increasing importance of a genetic predisposition to thrombophilia. Acquired hemostatic factors include pregnancy and the puerperium, oral contraception, hormone-replacement therapy, malignant tumors, and antiphospholipid syndromes. Important environmental risk factors include hospitalization with previous surgery or trauma, confinement in a care facility, neurologic disease or paraplegia after stroke, current or recent central venous catheter or transvenous pacemaker, and long airplane flights. Internists may be confused about the risk of PE after ventilation/perfusion (VQ) imaging. This may well arise from their use of the relative risk of PE after a low-probability category scan rather than the absolute risk obtained by incorporating the PE prevalence for their particular patient in the risk analysis. Ideally, personal communication with an experienced referring physician provides this clinical information for nuclear medicine. Diagnostic tools or checklists can be used as an alternative. A general knowledge of the natural history of VTE will encourage the nuclear medicine physician to provide an appropriate clinical signal to complement VQ categorical analysis. Combination of these 2 dynamic elements of the art and science of VQ scan reporting-the clinical pretest probability of PE and lung scan category-will permit an accurate prediction of the absolute risk of PE posttest.
 ...
PMID:The natural history of venous thromboembolism: impact on ventilation/perfusion scan reporting. 1210 97

A 10-year-old Turkish boy was admitted with mild right spastic hermiplegia. First, he experienced sudden numbness and weakness in the right extremities at the age of 2 years and was diagnosed with right hemiparesis. His parents were generally healthy and non-consanguineous. His mother suffered from deep vein thrombosis of the left lower extremity during pregnancy and had recurrent fetal loss. At the age of 10 years, a thrombophilia marker examination revealed that plasma-free protein S was 49.3% (normal range = 70-123%), and factor VIII level was found to be 470 IU/dL (normal = 150 IU/dL). The patient and his two siblings were found to be heterozygous for factor V Leiden mutation. His mother was also heterozygous for factor V Leiden mutation and had protein S deficiency. A combination of protein S deficiency, factor V Leiden mutation, and a high level of factor VIII was detected in our patient. After his first attack at the age of 2 years, in spite of no prophylaxis, he did not experience any other ischemic insult. To our knowledge, this is the first patient with these combinations of genetic defects and ischemic stroke to be reported in the literature.
 ...
PMID:Combined genetic defects in a child with ischemic stroke: case report. 1226 33

Plasma D-dimer concentration rises more than 100-fold during acute deep vein thrombosis, but there are no prospective data concerning D-dimer as a risk factor for incident venous thrombosis in a general population. Incident venous thrombosis was ascertained in 2 prospective observational studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Of 21 690 participants enrolled between 1987 and 1993, after 8 years of follow-up, D-dimer was measured using baseline stored plasma of 307 participants who developed venous thrombosis and 616 who did not. Relative to the first quintile of the distribution of D-dimer, the age-adjusted odds ratios for future venous thrombosis for the second to fifth quintiles of D-dimer were 1.6, 2.3, 2.3, and 4.2, respectively (P for trend <.0001). Following added adjustment for sex, race, body mass index, factor V Leiden, prothrombin 20210A, and elevated factor VIII coagulant activity (factor VIII:c), these odds ratios were 1.5, 2.1, 1.9, and 3.0, respectively (P for trend <.0001). Among those with idiopathic thrombosis or secondary thrombosis unrelated to cancer, the adjusted fifth quintile odds ratios were 3.5 and 4.8, respectively. By contrast, D-dimer in the fifth versus first quintile was not related to occurrence of cancer-associated thrombosis (odds ratio, 1.1). Odds ratios for elevated D-dimer were consistently elevated in subgroups defined by age, sex, race, duration of follow-up, and thrombosis type (deep vein thrombosis or pulmonary embolus). D-dimer is strongly and positively related to the occurrence of future venous thrombosis.
 ...
PMID:Fibrin fragment D-dimer and the risk of future venous thrombosis. 1465 70

Spinal cord injured patients are at increased risk of developing deep vein thrombosis (DVT). Whether these patients have increased blood levels of prothrombotic markers remains to be clarified. In general, the risk of developing DVT is highest in the morning hours. In healthy humans, several haemostatic and fibrinolytic parameters exhibit circadian variations, but it is not known whether this also applies to those with spinal cord injury. The aim of the present study was to examine possible circadian variations in prothrombotic markers in tetraplegic patients. We studied six patients with complete tetraplegia and eight control subjects with repetitive blood sampling over a 24 h period. While the control subjects showed marked circadian variations in factor VIII activity, prothrombin fragments 1+2 and D-dimer levels, the tetraplegic patients did not (P < 0.05). Circadian variation in plasminogen activator inhibitor type-1 was present in both groups, being most marked (P < 0.05) in tetraplegia. We conclude that the circadian variations of several factors of the haemostatic and fibrinolytic systems are impaired in spinal cord injury. This could possibly reflect a deregulated autonomic nervous system, leading to a dysfunctional link between central and peripheral circadian oscillators.
 ...
PMID:Impaired circadian variations of haemostatic and fibrinolytic parameters in tetraplegia. 1247 82

Acquired hemophilia A is a life-threatening immune-mediated hemorrhagic disorder that is most often found in individuals older than 50 who present with an unexplained activated partial thromboplastin time (aPTT) prolongation and clinically significant bleeding. The prolonged aPTT associated with acquired hemophilia A reflects factor VIII activity deficiency due to neutralizing or clearing autoantibodies. Deep venous thrombosis, in contrast, is a veno-occlusive disorder associated with several distinct hypercoagulable states that can result in significant morbidity and mortality due to pulmonary embolism, thrombus extension, and the post-thrombotic syndrome. A prolonged aPTT in the setting of thrombosis may reflect the presence of a lupus anticoagulant. In the absence of accurate diagnosis and the immediate institution of specific therapy, both disorders can be fatal. Three cases of acquired factor VIII inhibitors that included a prolonged aPTT, bleeding, and duplex ultrasound evidence of deep venous thrombosis are presented. The diagnostic and therapeutic challenges posed by these cases as well as a proposed mechanism by which pathologic thrombosis can develop in a patient with a life-threatening bleeding disorder are discussed.
 ...
PMID:Simultaneous deep venous thrombosis and acquired factor VIII inhibitor. 1251 88

Deep vein thrombosis (DVT) is a common disease with an annual incidence of about 1 in 1000. Many risk factors have already been studied, both genetic and acquired. It is unclear whether obesity affects thrombotic risk in unselected patients. Obesity is common, with a prevalence of 20-25% and may therefore have a considerable impact on the overall incidence of thrombosis. We evaluated the risk of thrombosis due to overweight and obesity using data from a large population based case-control study. Four hundred and fifty-four consecutive patients with a first episode of objectively diagnosed thrombosis from three Anticoagulation Clinics in the Netherlands were enrolled in a case-control study. Controls were matched on age and sex to patients and were introduced by the patients. All patients completed a standard questionnaire and interview, with weight and height measured under standard conditions. The associations of obesity with clotting factor levels were studied to investigate possible mechanisms. Obesity (BMI >/=30 kg/m(2)) increased the risk of thrombosis twofold (CI95: 1.5 to 3.4), adjusted for age and sex. Obese individuals had higher levels of factor VIII and factor IX, but not of fibrinogen. The effect on risk of obesity was not changed after adjustment for coagulation factors levels (fibrinogen, F VIII, F IX, D-dimer). The relative risk estimates were similar in different age groups and in both sexes, indicating a larger absolute effect in older age groups. Evaluation of the combined effect of obesity and oral contraceptive pills among women aged 15-45 revealed that oral contraceptives further increased the effect of obesity on the risk of thrombosis, leading to 10-fold increased risk amongst women with a BMI greater than 25 kg/m(2) who used oral contraceptives. Obesity is a risk factor for deep vein thrombosis. Among women with a BMI greater than 25 kg/m(2) the synergistic effect with oral contraceptives should be considered when prescribing these.
 ...
PMID:Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. 1262 33

Venous thrombosis is a very rare occurrence in patients with haemophilia A. The majority of these cases occurred during or after the administration of clotting factor concentrates. We report the case of a patient with severe haemophilia A, who spontaneously developed a deep venous thrombosis (DVT). The thrombosis occurred in the superficial femoral vein with an extension in the profunda femoris vein. Neither any local anatomic compression nor any predisposing thrombophilic risk factors were identified. Treatment with recombinant factor VIII at prophylactic doses associated with unfractionated heparin led to a successful resolution. This case illustrates the possibility for severe haemophilia patients to develop authentic spontaneous DVT without anti-haemophilic treatment and predisposing risk factors.
 ...
PMID:Spontaneous proximal deep vein thrombosis in a patient with severe haemophilia A. 1294 84

High factor VIII (FVIII) levels are known to be a risk factor for deep venous thrombosis, but the mechanisms responsible for high FVIII levels remain unclear. Here, a new phenotype "FVIII level residuum" (FVIII-R) was defined in order to eliminate the impact of common determinants on FVIII levels. We studied 13 families of patients with thrombosis and reproducibly high FVIII levels of unknown origin. Since familial clustering was evident, we looked for a possible genetic basis. A genome scan was performed with 402 evenly spaced microsatellite markers. A quantitative linkage analysis using variance component methods showed suggestive evidence for linkage of FVIII-R with a locus on chromosome 8 (logarithm of odds [LOD] = 2.1). In addition, we performed parametric exploratory linkage analysis of dichotomized FVIII-R, taking a parent-of-origin effect into account. Single-trait-locus MOD-score analysis showed suggestive evidence for linkage under an imprinting model at chromosomes 5 and 11. Furthermore, a 2-trait-locus analysis under a multiplicative model for the loci of chromosomes 5 and 11 yielded a remarkable LOD of 4.44. It confirmed the finding of paternal imprinting, obtained by single-trait-locus analysis, at both loci. Our results suggest that high FVIII levels in venous thromboembolism represent a complex trait caused by several genetic factors.
 ...
PMID:High factor VIII levels in venous thromboembolism show linkage to imprinted loci on chromosomes 5 and 11. 1535 85

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.
 ...
PMID:Ramifications of four concurrent thrombophilic mutations and one hypofibrinolytic mutation. 1549 23


<< Previous 1 2 3 4 5 6 7 8 Next >>