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)

Fibrinolysis triggered by t-PA bound to fibrin is one of the main antithrombotic mechanisms. Defects in the fibrinolytic system-decreased tissue-type plasminogen activator (t-PA) activity and elevated levels of plasminogen activator inhibitor (PAI-1), in patients with SLE have been associated with an increased tendency to thrombosis. In the present study, 43 patients with SLE fulfilling the ACR criteria for the disease, were studied for the presence of autoantibodies to fibrin-bound t-PA, i.e. the physiological active form of this plasminogen activator. A solution of 200 IU/ml of t-PA was incubated with solid-phase fibrin prepared as previously described (Anal Biochem 1986; 153; 201-210). Sera diluted 1:50 were incubated with fibrin-bound t-PA, the plates were then washed, and bound immunoglobulins were detected using a polyvalent peroxidase-labeled goat anti-human Ig. Plates coated with fibrin alone were used as controls. Sera were considered positive when A490/630 obtained with normal human sera in two independent test was greater than the mean plus 2 SD. Eleven of 43 (26%) SLE sera demonstrated antibody reactivity against fibrin-bound t-PA. Within the anti-t-PA positive group there was a higher proportion of SLE patients with severe Raynaud's phenomenon and thrombotic events when compared to the anti-t-PA negative group: 36% vs 6% and 18% vs 6% respectively. These results suggest that autoantibodies to fibrin-bound t-PA could play a role in the pathogenesis of vascular disease in some SLE patients.
Lupus 1996 Aug
PMID:Antibodies to fibrin-bound tissue-type plasminogen activator in systemic lupus erythematosus are associated with Raynaud's phenomenon and thrombosis. 886 98

Primary hypercoagulable states are hereditary disorders that result in arterial and venous thromboses. The purpose of this report is to present three patients with hypercoagulable states, and offer current guidelines for diagnosis and treatment. Primary hypercoagulable disorders such as antithrombin III, protein C and protein S deficiencies, fibrinolytic disorders such as decreased plasminogen levels and plasminogen activator deficiency, and antiphospholipid syndromes such as anticariolipin antibody and lupus anticoagulants will be reviewed. We will emphasize clinical characteristics that should prompt evaluation for hypercoagulation, appropriate laboratory tests for hypercoagulable disorders, and treatment. Other secondary and recently investigated hypercoagulable disorders, including heparin-associated thrombocytopenia, homocystinemia, lipoprotein (a), plasminogen activator inhibitor, and factor V Leiden, will also be reviewed.
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PMID:The surgical implications of primary hypercoagulable states. 904 71

Quantitative reverse transcription polymerase chain reaction and in situ hybridization were employed to investigate the expression of tissue-type and urokinase-type plasminogen activators (t-PA and u-PA, respectively), of their specific inhibitor (PAI-1), and of the procoagulant molecule tissue factor (TF) in tissues from mice that develop autoimmune disease (MRL lpr/lpr). A dramatic increase in PAI-1 activity in plasma and in PAI-1 mRNA in the kidneys was observed in these mice, and this increase appeared to correlate with the progression of lupus nephritis. The increase in PAI-1 mRNA was relatively specific for the kidney as little or no change was observed in most other tissues. One exception was the brain where PAI-1 mRNA was also significantly higher in the diseased mice. In addition to these changes in PAI-1, decreases in u-PA mRNA and increases in TF mRNA were demonstrated in kidneys from the lupus-prone mice. These changes also correlated with the development of lupus nephritis and with spontaneous glomerular and peritubular fibrin deposition in the nephritic kidney. In this regard, the MRL lpr/lpr mice were found to be considerably more sensitive to endotoxin than the normal controls, developing fibrin deposits in the kidneys and other tissues at 10- to 20-fold lower concentrations of this toxic agent. The increase in PAI-1 and TF mRNAs and the decrease in u-PA mRNA in the kidneys of MRL lpr/lpr mice suggests that changes in the expression of these genes may promote the formation of microthrombi and thus contribute to the progression of lupus nephritis in this model.
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PMID:The kidneys of mice with autoimmune disease acquire a hypofibrinolytic/procoagulant state that correlates with the development of glomerulonephritis and tissue microthrombosis. 928 21

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

We describe here the broad spectrum of acute renal insufficiency occurring in the course of human immunoinsufficiency virus infection. In our renal unit in Tenon hospital, 90 human immunoinsufficiency virus-infected adult patients were admitted for acute renal insufficiency between June 1988 and December 1996. Sixty out of them had a pathological diagnosis. The remaining patients did not have renal biopsy because of obstructive renal failure (n = 2), bleeding risk (n = 11), or clinically evident hypovolemic and/or sepsis-related acute tubular necrosis (n = 17). Nine different causes of acute renal insufficiency were listed. Human immunoinsufficiency virus-associated nephropathy, the most specific human immunoinsufficiency virus-related renal disease, which was diagnosed in 14 patients, is characterized by focal and segmental glomerulosclerosis with an important hyperplasia and/or proliferation of podocytes and huge tubular distension. The rapid progression to end-stage renal failure was not a constant feature since 10/14 patients had a partial renal recovery. Hemolytic-uremic syndrome was the other major cause of acute renal failure in these patients (32 cases) and was found to be associated with active cytomegalovirus infection. Cytomegalovirus-infected cells were present in half of the renal biopsies performed in this group of patients. Furthermore, these patients had an increased plasma tissue-type plasminogen activator activity whereas its type 1 inhibitor was not significantly increased, as opposed to non human immunoinsufficiency virus-associated hemolytic-uremic syndrome. Half of the patients had a complete renal recovery. The other causes of acute renal insufficiency were 1) intratubular deposition of either drugs (Adiazine, Foscavir, Indinavir) in 13 patients, or monoclonal light chain in one patient with B cell-lymphoma; 2) lupus-like glomerulonephritis characterized in one case by a complete clinical remission after 6 month-treatment by antiproteases; 3) acute tubular necrosis. In this setting, rhabdomyolysis could reveal HIV infection. The heterogeneity of renal diseases could be explained by the variation of human immunoinsufficiency virus-associated infections along time and by the different drugs which permit a better survival. We can hypothesize that new HIV-associated diseases will occur with the long term use of antiproteases.
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PMID:[Human immunodeficiency virus and acute renal insufficiency]. 961 98

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

Various coagulation abnormalities were reported in HIV-infected patients. Cases of severe thrombocytopenia were first observed in contaminated homosexual males, as well as prolonged APTT due to the presence of lupus-like anticoagulant with a frequency in the range 8 to 70% of the studied patients. Even if lupus anticoagulant could be evidenced in asymptomatic patients, it frequently occurred during acute opportunistic infections such as Pneumocystis carinii. More recently, increased prevalence of protein S and heparin cofactor II deficiency, two physiological coagulation inhibitors were demonstrated in HIV-infected patients. The same applied for hypoalbuminemia-related fibrin polymerization defects which induced prolonged thrombin and reptilase clotting times. Abnormalities of the fibrinolytic system were also reported, such as increased levels of both tissue-type plasminogen activator and type 1 plasminogen activator inhibitor or decreased levels of histidine-rich glycoprotein. Even if the acute phase response could play a key-role, the pathogenesis of these abnormalities is not fully understood, so far. In addition, their clinical consequences have not been extensively investigated, but hemorrhage appeared to be uncommon. Moreover, D-dimer levels were found increased in HIV-infected patients, suggesting that HIV-infection might be associated with a so-called prethrombotic state, which could lead to clinical thrombosis in some HIV-infected patients (2%).
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PMID:[Hemostasis and human immunodeficiency virus (HIV) infection]. 975 40

We examined activated partial thromboplastin time, kaolin clotting time, mixing with normal plasma in kaolin clotting time, dilute Russell's viper venom time, dilute Russell's viper venom time at high lipid concentrations, anti-phospholipid antibodies, and anti-cardiolipin-beta2-glycoprotein I complex antibody in 135 patients with prolongation of activated partial thromboplastin time and diagnosed 86 patients positive for lupus anticoagulant. The sensitivity of activated partial thromboplastin time and dilute Russell's viper venom time/dilute Russell's viper venom time-high lipid concentrations ratio for lupus anticoagulant were markedly high, but the specificity of activated partial thromboplastin time for lupus anticoagulant was not markedly high. The specificity, but not the sensitivity, of kaolin clotting time-mixing with normal plasma in kaolin clotting time was markedly high. In summary, dilute Russell's viper venom time to dilute Russell's viper venom time-high lipid concentrations ratio gave high sensitivity as well as specificity, being the only assay to confirm this. Of the patients positive for lupus anticoagulant, 25% were positive for anti-phospholipid antibodies and 17% were positive for anti-cardiolipin-beta2-glycoprotein I complex antibody. Of the lupus anticoagulant-positive patients with thrombosis, 45% were positive for anti-phospholipid antibodies, 35% were positive for anti-cardiolipin-beta2-glycoprotein I complex antibody, 60% were positive for both anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody, and only 17% were negative for anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody. These findings suggest that lupus anticoagulant can be diagnosed by dilute Russell's viper venom time/dilute Russell's viper venom time-high lipid concentrations ratio, and that thrombosis in lupus anticoagulant-positive may be predictable from both anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody. Plasma tissue type plasminogen activator level in lupus anticoagulant patients was significantly increased, and plasma tissue type plasminogen activator and fibrin-D-dimer levels in lupus anticoagulant-positive patients with thrombosis were significantly higher than in those without thrombosis, suggesting that the diagnosis of thrombosis by hemostatic markers might be important in lupus anticoagulant.
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PMID:Coagulation tests and anti-phospholipid antibodies in patients positive for lupus anticoagulant. 1089 74

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.
Lupus 2001
PMID:Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model. 1123 22

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


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