Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing osteonecrosis (ON). Twenty-six patients with SLE were studied. Fifteen of these had ON and 11 did not. The latter were used as control subjects. Various coagulation analytes including antithrombin III (ATIII) activity, protein C activity, protein S activity, alpha 2-antiplasmin activity, anticardiolipin antibodies (aCL), plasminogen activator inhibitor (PAI-1) activity and tissue type plasminogen activator (tPA) antigen were measured using citrated plasma samples from the patients. A significant proportion (80%) of patients had at least one laboratory abnormality that has been associated with a thrombotic predisposition. ON was significantly associated with elevated levels of PAI-1 activity; it was also associated with elevated PAI-1/tPA ratio. There was no association between ON of SLE and abnormalities of the other measured coagulation analytes. These results suggest that defective fibrinolysis seems to be operative in the pathogenesis of ON associated with SLE. The defect appears to involve an imbalance between tPA and its inhibitor, PAI-1. This imbalance could represent an important risk factor in the pathogenesis of ON.
Lupus 1998
PMID:Association of osteonecrosis in systemic lupus erythematosus with abnormalities of fibrinolysis. 949 48

Abnormal expression of fibrinolytic genes [e.g., tissue-type and urokinase-type plasminogen activators (t-PA and u-PA) and their specific inhibitor (PAI-1)] and of the procoagulant molecule tissue factor (TF), has been reported in various types of renal diseases. In this review, the expression pattern of these genes was demonstrated in two murine models of renal disease. One is acute renal failure due to microthrombosis under septic conditions, using endotoxin-treated mice, and the other one is lupus nephritis observed in female MRL lpr/lpr mice. Quantitative reverse transcription-polymerase chain reaction analysis and in situ hybridization were employed to investigate the expression of their mRNAs in tissues from endotoxin-treated mice or from MRL lpr/lpr mice. A dramatic increase in PAI-1 activity in plasma and in PAI-1 mRNA in the kidneys was observed in both models, and this increase appeared to correlate with fibrin deposition in the renal microvasculature and with the progression of lupus nephritis. In addition to these changes in PAI-1, decreases in u-PA mRNA and increases in TF mRNA were demonstrated in the kidneys from lupus-prone mice as a function of age. Similar changes were also observed in the kidneys from endotoxin-treated mice. The induction of PAI-1 and TF, and the decrease in u-PA expression in the kidneys of lupus-prone or of endotoxemic mice may promote the formation of renal microthrombi and thus contribute to the progression of renal damage in these models.
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PMID:Renal expression of fibrinolytic genes and tissue factor in a murine model of renal disease as a function of age. 970 58

Thrombophilia is defined as an increased tendency to thrombosis and can be inherited or acquired. The thrombotic events in patients with inherited thrombophilia tend to occur at a young age, are often idiopathic, recurrent and may occur at unusual sites (e.g. mesenteric, portal and cerebral veins and in inferior vena cava). The most common of the hereditary defects appear to be antithrombin, protein C, protein S deficiency, which account for 10% of individuals presenting with venous thromboembolism, resistance to anticoagulant effect of activated protein C (APC-R), which is present in 17 to 64% of patients with thrombosis and prothrombin 20210 G-->A variant with 6% prevalence in patients with thrombosis. APC-R is due in 90% to the presence of factor V Leiden. Rarer defects include heparin cofactor II (HC II), plasminogen or tissue plasminogen activator deficiency (TPA), elevated plasminogen activator inhibitor-1 (PAI-1) and dysfibrinogenemia. The most common acquired defects are antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies). Hyperhemocystinemia is responsible as well for arterial as venous thrombosis. A substantial proportion of venous thrombotic events occurs spontaneously, i.e. without a precipitating event. Risk factors for thrombosis include surgery, trauma, immobility, congestive heart failure, pregnancy including puerperium and oral contraceptive usage. The thrombotic risk is increased in patients who are homozygous for factor V Leiden and markedly increased in patients with combined defects.
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PMID:[Thrombophilic states]. 1035 55

Although first-time miscarriages are usually caused by chromosomal defects, about 55% of recurrent miscarriages are caused by procoagulant defects that induce thrombosis and infarction of placental vessels. Of recurrent miscarriages, about 7% are caused by chromosome defects, 15% to hormonal defects, and 10% to 15% to anatomical defects. Recurrent miscarriage involves more than 500,000 women in the United States each year. During the past 4 years, 179 patients, prescreened for chromosomal, hormonal, and anatomical defects, and found to harbor none, underwent hemostasis defect evaluation. A total of 160 of these have been analyzed. A hemostasis defect was found in 150 of 160 women (n = 94% of screened women). The mean age was 33 years; the mean number of miscarriages before referral was three. All women with a procoagulant defect (149) were treated with preconception ASA at 81 mg/d, and unfractionated porcine heparin at 5000 U every 12 hours was added immediately postconception; both agents were used to term delivery. Only two of 149 patients failed therapy. The defects found were as follows: antiphospholipid syndrome, 67%; sticky platelet syndrome, 21%; tissue plasminogen activator (TPA) deficiency, 9%; factor V Leiden, 7%; high PAI-1, 6%; protein S, 5%; high LP(a), 3%; AT, 2%; protein C, 1%. Thirty-eight patients had more than one defect. In the group with antiphospholipid syndrome, 24% only had a subgroup antibody (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol) or antiphosphatidic acid antibody, in the absence of anticardiolipin antibody or lupus anticoagulant. This finding is similar to that recently reported in early age ischemic stroke patients (<50 years old). In summary, about 55% of patients with recurrent miscarriage harbor a procoagulant defect to account for placental vascular occlusion. More than 98% will have a normal term delivery with preconception aspirin (ASA) and addition of postconception heparin to term. Patients should be screened by an obstetrician or by reproductive specialists for hormonal and anatomic defects before initiating a procoagulant evaluation; if such prescreening is done, the yield of a defect is high and appropriate therapy leads to an excellent outcome.
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PMID:Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects: prevalence, treatment and outcome results. DRW Metroplex Recurrent Miscarriage Syndrome Cooperative Group. 1089 70

The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a 287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene. Thus, the homozygous deletion (D/D genotype) could cause chronic vasoconstriction, arterial hypertension and, possibly, coronary artery disease. Also, the increase in plasminogen activator inhibitor-1 level and impaired fibrinolysis were related with the D/D genotype. The D allele has been recently associated with venous thrombosis among African-American men as well as among patients that underwent elective total hip replacement. We assess the risk of venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene polymorphism in a Caucasian population by means of a case-control study. We genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the same geographic area. The observed difference in D allele frequencies between patients (0.56) and controls (0.62) was nonsignificant overall; however, statistical significance (P = 0.05) was found by considering the recessive hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for the D allele was close to 1 for the dominant hypothesis, both considering gender and recurrent tendency; however, it was protective in men regarding the recessive hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele distribution was similar among the 46 thrombophilic patients (antithrombin, protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not support the hypothesis that the deletion allele (D) of the ACE gene could be a significant risk factor for VTE, being protective in men.
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PMID:Risk of venous thromboembolism associated with the insertion/deletion polymorphism in the angiotensin-converting enzyme gene. 1093 9

Long-term survival of renal transplant recipients appears to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. In order to investigate the prevalence of new hemostasis-related risk factors for venous and arterial thrombosis, we investigated 63 renal transplant recipients and 66 age- and sex-matched control subjects. We assayed antiphospholipid antibodies [lupus anticoagulant (LA) and anticardiolipin antibodies (aCL)], lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and total homocysteine (tHcy) levels. We found a significantly higher prevalence of positivity for LA (P < 0.001); no difference was detected in the prevalence of aCL between patients and controls. PAI-1 levels were significantly higher in renal transplant recipients than in controls [12.3 IU/ml (2-45.5) vs 7.9 IU/ml (4-18.0); P < 0.0001] with an odd ratio (OR) of 11.8 (4.9-28.5) in univariate analysis and of 5.8 (2.1-15.4) in multivariate analysis. Lp(a) levels were higher in patients then in controls [159 mg/l (1-992) vs 100.5 mg/l (10-412); P < 0.005] with an OR of 5.9 (1.9-18.4) in univariate analysis and of 3.5 (0.9-13.4) in multivariate analysis. Fasting levels of tHcy were significantly higher in renal transplant recipients [7.0 micromol/l (4.0-68) vs 8.1 micromol/l (2.0-24.0); P < 0.00001] with an OR of 40.4 (14.7-111) in univariate analysis and of 33.1 (11.1-115.5) in multivariate analysis. After methionine loading test, we documented levels of tHcy above the 90th percentile of controls in 60/63 patients (95%). Finally, we found a significant correlation between tHcy and PAI-1 plasma levels (r = 0.76; P < 0.000001). Our results show a high prevalence of hemostasis-related risk factors for arterial and venous thrombosis in renal transplant recipients, suggesting the need for the investigation of these patients for the presence of these risk factors in order to improve their long-term survival and to tailor therapy.
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PMID:Risk factors for cardiovascular disease in renal transplant recipients: new insights. 1111 46

The etiologic role of thrombotic and fibrinolytic disorders in Perthes' disease has not been determined. A case control study was conducted to determine whether thrombotic and fibrinolytic disorders are associated with Perthes' disease. Twenty-six patients with Perthes' disease were matched with 26 control patients for gender, age (2-year range), and time of presentation (1-year range). Thrombotic disorders were investigated for protein C activity, protein S activity, antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus anticoagulant. Fibrinolytic disorders were investigated for tissue-plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-1 to tissue plasminogen activator ratio, lipoprotein (a), and plasminogen. The activity of protein C, which suppresses factor Va and leads to an increase of coagulant activity when decreased, was increased in patients. There were no significant differences in the levels of other factors between the patients and controls. No evidence was found to prove a relationship between Perthes' disease and thrombotic or fibrinolytic disorders in the patients in the current study.
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PMID:Role of thrombotic and fibrinolytic disorders in the etiology of Perthes' disease. 1201 5

We have recently described the novel autoantigen plasminogen activator inhibitor (PAI-1) in systemic lupus erythematosus (SLE). The aim of this study was to determine the prevalence and clinical significance of anti-PAI-1 autoantibodies in patients with SLE. Autoantibodies to recombinant PAI-1 were measured in retrospective sera of 48 lupus patients by immunoassay in order to assess their clinical significance. This showed that 71% of sera from 48 lupus patients had significantly elevated anti-PAI-1 autoantibodies as compared with normal control subjects (P < 0.0001). There was a weak but significant (P < 0.043) correlation with anti-dsDNA autoantibodies. In longitudinal studies, autoantibodies against PAI-1 correlated with clinical parameters measured by the BILAG disease activity index including global clinical score. Our study demonstrates the high frequency of novel autoantibodies to PAI-1 in patients with lupus. The serial clinical correlations with anti-PAI-1 autoantibodies also support the hypothesis that these autoantibodies may play a pathogenic role in lupus.
Lupus 2003
PMID:The prevalence and clinical significance of autoantibodies to plasminogen activator inhibitor 1 in systemic lupus erythematosus. 1294 21

Some studies have suggested that thrombotic and fibrinolytic disorders may be etiologic causes of osteonecrosis of the femoral head. A case-control study was done to determine whether these disorders are associated with osteonecrosis of the femoral head in East Asian patients with nontraumatic osteonecrosis of the femoral head. Twenty-four consecutive patients who had been diagnosed as having nontraumatic osteonecrosis of the femoral head were matched with 24 control subjects for gender, age (1-year range), and the time of presentation (1-year range). Thrombotic factors including protein C activity, protein S activity, antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus antibody were investigated. Fibrinolytic factors including tissue-plasminogen activator, plasminogen activator inhibitor-1, tissue-plasminogen activator and plasminogen activator inhibitor-1 ratio, lipoprotein (a), and plasminogen also were investigated. There were no significant differences in the levels of thrombotic and fibrinolytic factors. In eight patients with idiopathic osteonecrosis, anticardiolipin antibody immunoglobulin G, an antiphospholipid antibody which is associated with thrombotic phenomena, was lower than that in respective control subjects. These data do not confirm an etiologic role for thrombotic and fibrinolytic disorders in East Asian patients with nontraumatic osteonecrosis of the femoral head.
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PMID:Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral head. 1464 26

Arterial thrombosis results from endovascular injury and, to a lesser extent, alterations in hemostatic equilibrium. Although multiple hereditary and acquired hemostatic risk factors have been described in the pathophysiology of venous thrombosis, the degree and type of abnormalities that contribute to arterial thrombosis are less well understood. Endothelial cell injury with the elaboration of proinflammatory mediators stimulates the process of arterial thrombosis. Although this is most often the result of endovascular injury attributable to atherosclerotic disease, other disease states can elicit a similar response as well. Similarly, once thrombosis has been initiated, variations in the activity of coagulation proteins and endogenous anticoagulants, as well as the kinetics of platelet aggregation, may alter the effectiveness of thrombus formation. Epidemiological studies have identified several acquired or inherited states that may result in endothelial damage or altered hemostatic equilibrium, thereby predisposing patients to arterial thrombosis. These include hyperhomocysteinemia, elevated C-reactive protein, antiphospholipid antibodies, elevated fibrinogen, Factor VII, plasminogen activator inhibitor-1 (PAI-1), hereditary thrombophilias, and platelet hyper-reactivity. This review explores our present understanding of these risk factors in the development of arterial thrombotic events. At present, the literature supports a role for hyperhomocysteinemia, elevated C-reactive protein, and elevated fibrinogen as risk factors for arterial thrombosis. Similarly, the literature suggests that lupus anticoagulants and, to a lesser extent, elevated titers of cardiolipin IgG antibodies predispose to arterial vascular events. In certain subsets of patients, including those with concomitant cardiac risk factors, <55 years of age, and women, hereditary thrombophilias such as carriership of the factor V Leiden and the prothrombin G20210A mutations may confer a higher risk of arterial thrombosis. However, the data on Factor VII, PAI-1, and platelet receptor polymorphisms are contradictory or lacking.
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PMID:Assessment of hemostatic risk factors in predicting arterial thrombotic events. 1642 55


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