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)

To investigate the hypothesis that diminished endothelial fibrinolytic activity contributes to the pathogenesis of thrombosis in patients with the lupus anticoagulant (LA), we assessed the ability of endothelium to release tissue-type plasminogen activator (t-PA) in response to standardized venous occlusion (VO) of the arm, and the extent of inhibition of t-PA, in 11 subjects with LA and a history of thrombosis and in 36 healthy normal subjects. The mean rise in plasma t-PA antigen after VO, the mean plasma free t-PA activity after VO, and the mean plasma t-PA inhibitor level prior to VO were not significantly different in subjects with LA and thrombosis and in normal subjects. Four subjects with LA and thrombosis (36%), and five of 36 healthy control subjects (14%) generated no detectable free t-PA activity after VO ("non-responders"); this difference was not statistically significant. All four "non-responders" with LA and thrombosis had normal t-PA antigen release after VO, indicating that the lack of detectable free t-PA activity after VO was due to increased inhibition of released t-PA. We conclude that abnormally reduced endothelial fibrinolytic activity is not present in the majority of subjects with LA and thrombosis. In the subset of subjects with LA and thrombosis who generate no detectable t-PA activity after VO, a stimulatory effect of LA on endothelial production of t-PA inhibitor cannot be excluded.
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PMID:Endothelial-dependent fibrinolysis in subjects with the lupus anticoagulant and thrombosis. 314 79

Fibrinolytic and other factors have been measured in 73 patients with systemic lupus erythematosus or related conditions to determine whether clinical thrombosis, a common feature of these disorders, is associated with defective fibrinolysis. Twenty five of 72 (35%) patients, compared with two of 22 (9%) controls, showed a low level of plasminogen activator activity in response to venous occlusion, suggesting decreased fibrinolytic potential. In addition, mean plasma levels of von Willebrand factor antigen and fibronectin were markedly raised in the patients (mean (SD) 384.5 (277)% and 727 (436) mg/l respectively) compared with healthy controls (100 (50)% and 306 (65) mg/l). These data suggest a degree of endothelial cell dysfunction. No clear correlation was found between a history of thrombosis and any plasma factor measured, except for prolongation of clotting tests suggestive of the 'lupus anticoagulant'.
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PMID:Indications of vascular endothelial cell dysfunction in systemic lupus erythematosus. 350 Jun 77

Some molecular defects of components of the coagulation or fibrinolytic system are associated with thromboembolism. One possibility is that physiologic inhibitors of the coagulation system have an abnormal function e.g. protein C, protein S, antithrombin III and cofactor II of heparin. Also a hindered activation of the fibrinolytic system may predispose to thrombosis; the impaired activation may be due to deficient synthesis and/or release of tissue-plasminogen activator, an increased level of its inhibitor or a functional defect of the plasminogen molecule. A few cases of congenital dysfibrinogenemia have been described in which the functional defects of the molecule are held responsible for recurrent thrombosis. An acquired thrombotic disorder is due to the presence of immunoglobulins which prolongs phospholipid-dependent coagulation by binding to epitopes of some phospholipids. This so-called lupus anticoagulant was originally described in patients with systemic lupus erythematosus but is a misnomer as it is more frequently encountered in patients without lupus.
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PMID:[Molecular defects of coagulation factors and of the fibrinolytic system associated with thromboembolism]. 354 55

Methods are described to measure fibrinolysis in healthy persons and in patients with systemic lupus erythematosus. Using the fibrin plate method, total fibrinolytic activity and vascular plasminogen activator were measured. (Total fibrinolytic activity expresses the fibrinolytic potential and consists of both the intrinsic [factor XII-dependent and independent] activities and the extrinsic activities [vascular or tissue type]. Vascular plasminogen activator, assessed in a separate assay, refers to the endothelium-derived component only.) In addition, the degree of inhibition by plasma of both urokinase-induced and of plasmin-induced fibrinolysis were analyzed. Vascular plasminogen activator levels were low in 63% of plasma samples from 55 patients with systemic lupus erythematosus. The level of an inhibitor of plasminogen activation was significantly elevated in 87% of patients and levels of an inhibitor of plasmin were significantly elevated in 29%. The nonspecific serine protease inhibitors, including alpha 2-macroglobulin, were within the normal range in all patients. The natures of inhibitor of plasminogen activation and plasmin inhibitor were studied further. Using both the fibrin plate and the lysis time methods, the data indicated that the urokinase-inhibiting activity increased with time of incubation of plasma-enzyme mixtures, whereas the plasmin inhibiting activity did not. Elevated levels of plasmin inhibitor measured with the fibrin plate method correlated well with prolonged lysis times. Results using the chromogenic substrate S-2251, commonly used as a simple and specific assay for antiplasmin, agreed reasonably well with those using the fibrin plate method, but elevated plasmin inhibitor levels could be quantitated with greater accuracy and sensitivity by the fibrin plate method. Studies with an antiserum directed against alpha 2-antiplasmin showed that inhibitor of plasminogen activation and plasmin inhibitor were different inhibitors, and that plasmin inhibitor was identical to alpha 2-antiplasmin. The abnormalities are discussed in the light of current knowledge on fibrinolysis and as possible mediators in the pathogenesis and perpetuation of lupus glomerulonephritis.
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PMID:Fibrinolysis in health and disease: severe abnormalities in systemic lupus erythematosus. 623

The designation of Antiphospholipid Syndrome was first applied by Harris in 1987, to a clinical status characterized by the detection of anticardiolipin and/or lupus anticoagulant with clinical thromboembolic manifestations. Recent advances in its study has shown that the inducing antigen is really a complex of phospholipid and protein. Therefore, it became clear that there is a need for a protein cofactor to the formation and action of antiphospholipid antibodies (APL). The authors present a detailed revision of the nature and specificity of APL, described as its proteic counterpart. Their action is surely conditioned by the specific protein involved with phospholipids, as it may be with Beta 2-Glycoprotein 1, Prothrombin, Protein c and s, Anexin V and the association of plasminogen and t-PA. The isotype of immunoglobulins is also very heterogeneous, since it was detected as IgG as well as IgA and IgM immunoglobulins. Furthermore, they can coexist in the same patient and with no clear relationship with thromboembolic manifestations. These aspects demonstrate well the greater variability that is found in these patients in relation to clinical and laboratory manifestations of the disease. For laboratory diagnosis, micro ELISA systems were developed, allowing the identification of antiphospholipid immunoglobulins with relative specificity and accuracy. Finally, the most frequent clinical expression is described, emphasising the pitfalls of clinical and laboratory diagnosis of the antiphospholipid syndrome.
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PMID:[Antiphospholipid immunization syndrome and thrombosis]. 771 5

Endothelial cell damage in systemic lupus erythematosus (SLE) was evaluated by measuring fibrinolytic activity and von Willebrand factor levels. Tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PAI) activity, and von Willebrand factor antigen (vWF:Ag) and activity (vWF:RCof) were measured in 21 SLE patients (12 of whom were therapy free) and 22 controls. In addition, the relationship between such parameters and Raynaud's phenomenon, disease activity [according to personal criteria, Systemic Lupus Activity Measure (SLAM) and European Consensus Lupus Activity Measurement (ECLAM) scores] inflammatory indices [ESR, C-reactive protein (CRP), alpha 2-globulin], anticardiolipin antibodies and corticosteroid therapy was investigated. Lower levels of t-PA antigen (P = 0.003) and higher levels of vWF:Ag (P = 0.001) were found in SLE patients in comparison with controls. Moreover, t-PA antigen was lower (P = 0.02) in steroid-free patients in comparison with those taking steroids. No relationship was found between fibrinolysis and coagulation abnormalities and Raynaud's phenomenon, disease activity, inflammatory indices and anticardiolipin antibodies. Endothelial cell damage is probably a common feature in SLE patients; nevertheless, we were unable to clarify the nature of such abnormality. It is worth noting that low doses of steroids seem to be effective in improving endothelial cell function in SLE patients.
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PMID:Fibrinolysis and coagulation abnormalities in systemic lupus erythematosus. Relationship with Raynaud's phenomenon, disease activity, inflammatory indices, anticardiolipin antibodies and corticosteroid therapy. 772 97

The cause of thrombosis in the antiphospholipid syndrome (APS) is unknown. There have been reports of abnormalities in the antigenic levels or activity of endothelium-derived haemostatic factors, such as tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1); however the data from these studies are conflicting. We studied plasma from nine patients with APS; seven of them had a history of thrombosis, and three had systemic lupus erythematosus (SLE). We also studied nine matched control patients who had SLE without APS, and 14 healthy individuals. We measured t-PA, von Willebrand factor (vWF), anticardiolipin antibody (ACA) and anti-endothelial cell antibody (AECA) levels by enzyme-linked immunoassay (ELISA), PAI-1 activity by a parabolic-rate chromogenic assay, and lupus anticoagulant (LA) activity by a standard mixing test. For t-PA and PAI-1, measurements were made on morning and evening plasma samples. The two groups of patients did not differ significantly with respect to age, sex, plasma lipids or anti-inflammatory drugs. Most APS patients (7/9) but none of the controls were taking warfarin. Between the APS and the control patients no significant differences were detected in t-PA, PAI-1, vWF or AECA levels. When APS patients were considered alone, vWF levels correlated positively with IgG ACA levels (r = 0.81, P < 0.01) and negatively with platelet count (r = -0.68, P < 0.05). There was no correlation between levels of ACA or LA activity and t-PA, PAI-1 or AECA. Compared with healthy volunteers, the diurnal variation of t-PA and PAI-1 was blunted in the two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelium-derived haemostatic factors and the antiphospholipid syndrome. 772 92

The aetiology of non-arteritic ischaemic optic neuropathy (ION) is multifactorial with local anatomical and systemic haemodynamic abnormalities both playing a role. A careful search for treatable vascular disease risk factors is required to allow rational therapy, to optimise the visual prognosis and to allow new insights into pathogenesis. We describe 7 cases in which there was an associated thrombophilic (prothrombotic) state; 4 had deficiencies of the physiological anticoagulants proteins C and S and antithrombin III and 2 had anti-phospholipid antibody (lupus anticoagulant) syndromes. A further patient had reduced levels of the physiological fibrinolytic agent tissue plasminogen activator (t-PA). In 5 patients other risk factors for small vessel occlusive disease were also present, and 4 had recurrent episodes of ION in the same eye. The visual prognosis in these patients may be improved by anticoagulation with warfarin.
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PMID:Coagulation abnormalities in ischaemic optic neuropathy. 801 26

Activated protein C (APC)-protein C inhibitor (PCI) complex and APC-alpha 1antitrypsin (alpha 1AT) complex levels were measured in 29 patients positive for lupus anticoagulant (LA). LA was considered positive if two of the following three criteria were fulfilled: (1) prolongation of the activated partial thromboplastin time, (2) prolongation of the kaolin clotting time (KCT) and KCT mixing test, and (3) prolongation of the dilute Russell's viper venom time (DRVVT) and DRVVT/DRVVT with high lipid concentration. Plasma thrombin-antithrombin III (AT-III) complex and plasmin-alpha 2-antiplasmin inhibitor complex levels in patients positive for LA were increased slightly, but not significantly, and FDP-D-dimer and t-PA levels were not markedly increased. Plasma PAI-1 level in the LA-positive patients was significantly increased compared with normal volunteers. AT-III activity, protein C antigen, PCI antigen, and protein S antigen levels in the LA-positive patients were virtually normal, while protein C activity was slightly, but not significantly, decreased. APC-PCI complex level was increased in all LA-positive patients, and was not detectable in patients with systemic lupus erythematosus and normal volunteers. APC-alpha 1AT complex was increased slightly, in only two LA-positive patients; it was not detectable in the other patients or in the normal volunteers. These findings suggest that patients positive for LA are in a hypercoagulable state and that protein C activity in such patients is decreased, due to the activation of this protein.
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PMID:Increased activated protein C-protein C inhibitor complex level in patients positive for lupus anticoagulant. 805 49

This article has stressed the common hereditary and acquired blood protein defects associated with thrombosis. The commonest hereditary defects appear to be antithrombin, protein C, and protein S deficiency, and the commonest acquired defects are anticardiolipin antibodies and the lupus anticoagulant. Therefore these are the defects that should first be looked for in an individual with unexplained thrombosis. If these commoner defects are not found, the rarer defects, including HC-II, plasminogen or t-PA deficiency, dysfibrinogenemia, or elevated PAI-1, should next be sought. The incidence of activated protein C cofactor deficiency is not yet clear but may also represent a common defect. Likewise, PAI-1 defects may, with time, be shown to be quite common. The importance of finding these defects has significant implications for therapy of the individual patient and for institution of family studies to identify, inform, and possibly treat others at risk. It is expected that as knowledge of hemostasis expands, more hereditary and acquired defects, such as elevated lipoprotein (a) or defects of extrinsic (tissue factor) pathway inhibitor may be associated with enhanced risks of thrombosis.
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PMID:Hypercoagulability and thrombosis. 817 Feb 63


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