Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We here present an easily standardizable and reproducible procedure which clearly separates lupus anticoagulants (LA) from coagulation factor inhibitors. This new LA neutralization test makes use of platelet-derived microvesicles which were prepared as follows: gel-filtered platelets (4 x 10(5)/microliters) were incubated with 60 microM of the calcium ionophore A23187 for 20 min at 37 degrees C. The vesicles were separated from the platelet aggregates by centrifugation at 1000 g for 10 min. The vesicle containing supernatant was then spun down at 15,000 g for 15 min, lyophilized and stored at -20 degrees C until used. The vesicles were resuspended in plasma from normal individuals, from patients with LA activity, from patients with factor VIII inhibitors, from patients with congenital factor deficiencies and from patients receiving oral anticoagulants or intravenous heparin. A kaolin clotting time was performed in the absence (KCT) or presence of these vesicles (KCTves) and the ratios of these times to their respective mean normal times were calculated. Segregation of LA patients from all remaining patients except heparinized ones could be made with a high degree of accuracy. A thrombin time was needed to separate LA from heparinized patients. The method was highly reproducible and only minor (negligible) differences in potencies were observed between different vesicle preparations. Both the intra-batch and the inter-batch coefficients of variations on the KCTves were lower than 6%.
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PMID:A new lupus anticoagulant neutralization test based on platelet-derived vesicles. 158 Dec 14

We are reporting a young lady with protracted deep vein thrombosis of her left leg which turned out to be antiphospholipid (anticardiolipin) antibody syndrome of ANA positive systemic lupus erythematosus. Lupus anticoagulant was demonstrated by prolongation of activated partial thromboplastin time and Russell's viper venom time. She had no anti-thrombin III deficiency.
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PMID:Antiphospholipid antibody syndrome of systemic lupus erythematosus presenting as deep vein thrombosis. 829 83

We studied the relationship between vascular complications and coagulation and fibrinolysis parameters in 75 subjects with collagen diseases. Thirty normal healthy persons served as controls. We found that patients with collagen diseases were in a state of a hypercoagulation and hyperfibrinolysis. In SLE (systemic lupus erythematosus) in particular, coagulation and fibrinolysis parameters appeared to be indices of vascular complications. Increases in the levels of thrombin-antithrombin III complex (TAT) and alpha 2-plasmin inhibitor-plasmin (PIP) were particularly associated with proteinuria, while increases in fibrinopeptide A (FPA) levels were associated with Raynaud's phenomenon. Administration of glucocorticoid seemed to improve the hypercoagulation and hyperfibrinolytic states of patients with collagen diseases. Analysis of the multimeric structure of von Willebrand factor (vWF) revealed a tendency for large and intermediate multimers (LIM) of plasma vWF to increase in SLE patients with accompanying vascular complications, whereas such increases were not observed in SLE patients without any vascular complications. Therefore, analysis of the multimeric structure of vWF appeared to be a useful indicator of vascular complications in collagen diseases.
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PMID:Plasma coagulation and fibrinolysis parameters in patients with collagen diseases, and analysis of the multimeric structure of von Willebrand factor (vWF). 175 53

Lupus anticoagulants (LAs) are antibodies which interfere with phospholipid-dependent procoagulant reactions. Their clinical importance is due to their apparent association with an increased risk of thrombo-embolic disease. To date there have been few assays for quantifying the specific activity of these antibodies in vitro and this has hampered attempts to purify and characterize these antibodies. Methods for determining phospholipid-dependent generation of thrombin and factor Xa are described. Isolated IgG fractions from 7 of 9 patients with LAs were found to reproducibly inhibit enzyme generation in these assay systems, permitting quantitative expression of inhibitor activity. Different patterns of inhibitory activity, based on the relative inhibition of thrombin and factor Xa generation, were found, further substantiating the known heterogeneity of these antibodies. These systems may prove helpful in further purification and characterization of LAs.
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PMID:Assays for phospholipid-dependent formation of thrombin and Xa: a potential method for quantifying lupus anticoagulant activity. 179 95

Plasmas from 16 patients that were found to be positive both for anticardiolipin antibodies (ACA) and lupus anticoagulants (LA) were incubated with liposomes that contained anionic phospholipids. In 11 of these plasmas, ACA could be cosedimented with the liposomes in a dose-dependent manner, whereas LA activity of the remaining supernatant was unaffected. LA activity of purified total IgG from 6 patients was measured in three different coagulation tests, using normal plasmas from different species. Prolongation of the aPTT, KCT and dRVV clotting times was observed only with normal plasma from human origin, not with bovine, rat or sheep plasma. Highly purified coagulation factors Xa, Va and prothrombin, both of human and bovine origin, were used to establish for two patient IgG's the effect of LA on the rate of thrombin formation in the presence and absence of lipid vesicles composed of 20 mole% phosphatidylserine and 80 mole% phosphatidylcholine. A strong and dose dependent inhibition by LA was observed only when human prothrombin was used as substrate in the prothrombinase complex in the presence of lipids. No inhibition was found when bovine prothrombin was used as substrate. The inhibitory effect observed in the presence of human prothrombin was independent of the source of factors Xa and Va, and was not found in the absence of lipid. Preliminary binding studies suggest that LA only associate with a lipid surface, provided that human prothrombin and calcium ions are present. These data indicate that LA are not directed to phospholipids alone, but presumably recognize an epitope which becomes exposed upon Ca(2+)-mediated binding of human prothrombin to phospholipids.
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PMID:Lupus anticoagulant IgG's (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. 179 7

The effect of sera and purified IgG isolated from plasma of 46 patients with systemic lupus erythematosus (SLE) and 9 healthy donors on the endothelial cell (EC) mediated protein C activation was investigated. Out of the 46 SLE sera used, 19 were antiphospholipid antibodies (aPL) positive. From 12 patients IgG was isolated, of which 6 contained aPL. EC were first incubated with IgG (7 mg/ml) or serum (1:1 diluted) for 1 h and then tested for their ability to promote protein C activation by thrombin, with the cells either in a monolayer or in a suspension. The normal range (mean of control values +/- 2 SD) of protein C activation was 80-120%. In contrast to others, we could not detect an inhibition of protein C activation by any of the patient IgG's or sera. The recently described cofactor for binding of antiphospholipid antibodies to phospholipids, beta 2-glycoprotein I, was purified and added to the purified IgG's. A combination of these two components did not inhibit the EC mediated protein C activation by thrombin. This study suggests that the inhibition of the protein C activation, mediated by EC, is not a general mechanism by which aPL related thrombosis can be explained.
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PMID:In vitro studies of antiphospholipid antibodies and its cofactor, beta 2-glycoprotein I, show negligible effects on endothelial cell mediated protein C activation. 179 12

Phospholipids bearing a proportion of anionic species such as phosphatidylserine are necessary to promote the anticoagulant potential of the protein C pathway. Factor Xa (200 or 350 pM) was found to activate protein C in a thrombomodulin-independent reaction requiring only phospholipids in Al(OH)3,-adsorbed plasma resupplemented with physiological concentrations of protein C (70 nM) and protein S (130 nM). All experiments were performed in the presence of an excess of hirudin. The activity of activated protein C was assessed by the survival of factor Va. The optimal phospholipid concentration range was 5 to 25 microM with a proportion of phosphatidylserine of 50% (mol/mol) resulting in a half-life of factor Va of 7.5 min in the absence of protein S and 4.2 min in its presence. Dns-EGR-Xa, an inactive derivative of factor Xa, behaved as an apparent protector of factor Va. When replacing factor Xa, thrombin at 10 nM was not an efficient protein C activator in the absence of purified human placenta thrombomodulin. In the presence of 100 pM activated protein C, factor Va half-life was 2 min in the absence of protein S and 1.1 min in its presence in the above optimal phospholipid concentration range. The presence of protein S allowed reduction of phospholipid requirements. Annexin-V (placental anticoagulant protein-I), a potent phospholipid antagonist, fully protected factor Va from degradation by phospholipid-dependent mechanisms. Factor Va was partially protected in the plasma of a patient having experienced thrombosis associated with lupus-like anticoagulant and anti-phospholipid auto-antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The catalytic role of anionic phospholipids in the activation of protein C by factor Xa and expression of its anticoagulant function in human plasma. 179 56

Thrombomodulin (TM) is a constituent glycoprotein of endothelial cell membrane, and soluble TM is present also in plasma and urine. It was revealed by experiments using cultured HUVEC in vitro that TM is released from endothelial cell membrane not with monensin, thrombin, fibroblast growth factor, interleukin-1 or endotoxin, but with H2O2 or endotoxin-treated granulocytes. And the release was suppressed by the coexistence of gabexate mesilate or superoxide dismutase. It was suggested that soluble TM was released from endothelial cell membrane by its injury and digested to multiple molecular forms by endogenous and granulocytic protease(s). TM level in circulation is increased in cases of SLE, MCLS, diabetic angiopathy. It was increased in cases of overt DIC and decreased to the normal level when the patient was recovered from DIC. TM level in circulation was also increased in cases of decompensated liver cirrhosis and markedly in cases of renal insufficiency. It was concluded that plasma TM is a parameter reflecting endothelial injury due to inflammation or metabolic disorders of vascular system. But the interpretation of increased plasma TM was difficult when renal insufficiency was complicated.
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PMID:[Soluble thrombomodulin: a specific parameter of endothelial injury]. 185 Dec 35

Increased thrombogenesis observed in systemic lupus erythematosus (SLE) is derived from multiple mechanisms, including: Enhanced coagulation factor VIII:VWf activity, lupus anticoagulants, anti-phospholipid antibodies, acquired deficiencies of natural anti-thrombotic mechanisms (protein C, protein S, anti-thrombin III), and impaired fibrinolytic mechanisms. We studied the fibrinolytic mechanisms of 18 patients with systemic lupus erythematosus, selected carefully to avoid other possible causes of abnormalities in the fibrinolytic activity. Despite the fact that the euglobulin lysis time in steady state was normal in all instances, disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system were found in all SLE patients: TPA activity was undetectable in all cases, whereas it was above 0.4 IU/ml in a control group. In 72 percent of patients, the undetectable TPA activity was correlated with abnormally high PAI activity; PAI levels were normal in all members of the control group, their mean value being 0.74 versus 8.63 IU/ml for SLE patients (P less than .01). Coagulation protein C deficiency was found in 3 patients (17%). Even though within normal range, fibrinogen levels were significantly higher in SLE than in normal controls (219 versus 192 mg/dl, P less than .01) and plasminogen levels were significantly higher in SLE than in controls (117 versus 78.2%, P less than .01). Cross-linked fibrin derivatives (D-D dimers) were negative in all patients with SLE. Sixty-eight percent of SLE patients had high levels of antiphospholipid antibodies, but no correlation with the disturbances of the TPA/PAI system was found. It is concluded that most patients with SLE display severe abnormalities in the TPA/PAI anti-thrombotic system and that these abnormalities may be related to the lupus thrombophilia, apparently multifactorial in its origin.
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PMID:Disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system in systemic lupus erythematosus. 190 23

The purpose of this study was to investigate whether the presence of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) patients was associated with particular laboratory or clinical features. Anticardiolipin antibodies were determined in 63 unselected SLE patients: 32 (50.8%) were found to be aCL positive and this positivity was significantly associated with the presence of lupus anticoagulant (p less than 0.003) and false positive VDRL reaction (p less than 0.001), but not with other haematological or biological markers. Thrombin-antithrombin III (TAT) complexes were found to be increased with disease activity, but no relationship was found between TAT complexes and the presence or absence of aCL. In this study a statistically significant association was found between aCL positivity and arterial thromboembolic events, but not with venous thrombotic complications. In summary half of SLE patients had aCL and the presence of these antibodies was associated with other antiphospholipid antibodies and with arterial thromboembolic events.
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PMID:Laboratory and clinical features in systemic lupus erythematosus patients with or without anticardiolipin antibodies. 191 Feb 14


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