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)

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

To elucidate the mechanism of vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant changes in factors associated with haemostasis were investigated. The lupus anticoagulant was associated with an increased incidence of thrombosis, particularly cerebral thrombosis. Concentrations of fibrinopeptide A and fibrinopeptide B beta 15-42 were significantly raised in the plasma of patients with systemic lupus erythematosus and the anticoagulant compared with concentrations in patients without the lupus anticoagulant. The tendency towards formation of thrombosis was not found in all lupus patients with the anticoagulant, however. Concentrations of thromboxane B2 were remarkably raised in the plasma of the two patients with the lupus anticoagulant who had recently had thrombosis. Concentrations of 6-keto-prostaglandin F1 alpha, protein C, antithrombin III, and plasminogen were similar in both groups. No significant decrease in serum stimulatory activity on prostacyclin production by cultured aortic endothelial cells was noted in lupus patients with the anticoagulant, but inhibition was present in the two patients with recent thrombosis. These results indicate that although patients with the lupus anticoagulant are not always in a hypercoagulable state, haemostatic abnormalities found in some patients with the anticoagulant may be predictive of thrombotic events.
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PMID:Haemostatic factors associated with vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant. 190 17

Six monoclonal antibodies for human thrombomodulin (TM) were prepared. All of them recognized an elastase-digested fragment of TM which contains 6 epidermal growth factor (EGF)-like structural domains. We developed a one-step sandwich enzyme immunoassay for soluble TM by using 2 antibodies; one of them, which inhibited thrombin-binding to TM, was fixed to polystyrene balls, and the other, which did not inhibit the thrombin-binding, but inhibited the protein C-activating cofactor activity of TM, was used as peroxidase-labeled conjugate. The sensitivity of this assay was 1 microgram/l for soluble TM. The level of soluble TM was found to be significantly increased in sera of patients with systemic lupus erythematosus in comparison to the level in sera of healthy subjects.
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PMID:One-step sandwich enzyme immunoassay for soluble human thrombomodulin using monoclonal antibodies. 196 42

We have identified an inhibitor of the protein C anticoagulant pathway in the plasma of a patient with systemic lupus erythematosus and a history of recurrent deep vein thrombosis, fetal wastage, and seizures. The patient's plasma contained anticardiolipin antibodies as well as a weak lupus anticoagulant. Examination of this patient's plasma revealed normal levels of protein C and protein S antigen, normal levels of functional protein C, as well as essentially normal levels of every blood coagulation factor. In a modified prothrombin time assay, the activated protein C-mediated prolongation of the clotting time observed in normal plasma was not observed in this patient's plasma. Gel permeation chromatography of the patient's plasma revealed that the inhibitory material was a high molecular weight protein that coeluted with the IgM peak. The inhibitor did not appear to circulate as a complex with protein C, since the inhibitor could easily be separated from protein C during fractionation procedures, and did not interfere with the activation of protein C in plasma as assessed by a functional amidolytic assay. Our findings suggest that the recurrent thrombotic episodes observed in this patient may have occurred as a result of the patient's antiphospholipid antibody neutralizing specific phospholipids essential for the full expression of the anticoagulant activity of activated protein C.
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PMID:Impairment of the protein C anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis. 210 91

We determined the following coagulo-fibrinolytic activities in 24 patients with systemic lupus erythematosus (SLE) and 20 healthy adults: prothrombin time (PT), activated partial thromboplastin time (A-PTT), factor VIII: coagulant activity), von Willebrand factor antigen (vWF: Ag), antithrombin-III (AT-III), plasminogen (PLG), alpha 2 plasmin inhibitor (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (PIC), protein C (PC: activity and antigen concentration), and protein S (PS: total PS and free PS). PLG, AT-III, PC antigen concentration and total PS were significantly decreased in ten female controls as compared with ten male controls. Therefore, we used the ten healthy females as controls and excluded two male SLE patients in the analysis of the correlations of coagulo-fibrinolytic activities with lupus anticoagulant (LA), clinical and laboratory features in 22 female patients with SLE. In the SLE patients, PT was significantly shortened, while A-PTT was prolonged. PLG, PC activity and antigen, and total PS were significantly increased, and free PS levels were decreased in SLE. The shortened PT and decreased free PS suggest hypercoagulable states in SLE patients. A significant prolongation of A-PTT and a decrease of F VIII activity were observed in the six LA-positive SLE patients, and the results were considered as known effects of LA. Furthermore, vWF: Ag, AT-III and PC antigen levels were significantly increased in the LA-positive patients as compared with LA-negative patients. These changes indicate both vascular endothelial cell damages and a compensatory increase in coagulation inhibitors in the LA-positive patients.
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PMID:[Regulation of coagulo-fibrinolytic activity and lupus anticoagulants in systemic lupus erythematosus]. 212 31

The 5-year experience with a panel of laboratory tests designed to identify patients with high risk of thromboembolism was reviewed. This panel included an activated partial thromboplastin time and reptilase time as well as specific assays for antithrombin III, protein C, protein S, and plasminogen. One hundred and nine patients were evaluated by this panel. Conditions predisposing to thrombosis were identified in 24 of these patients and these conditions included: dysfibrinogenemia, lupus anticoagulant, and deficiencies of antithrombin III, protein C and protein S. The limitations of this panel are also discussed.
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PMID:Laboratory identification of conditions predisposing to thrombosis. 214 45

The range of disorders affecting the cerebral veins and sinuses is increasing and now includes blood disorders, abnormalities in the patterns of blood flow, and infiltrative or inflammatory conditions, all of which may promote thrombosis. We describe 10 patients with cerebral venous thrombosis: two had protein S deficiency, one had protein C deficiency, one was in early pregnancy, and there was a single case of each of the following: dural arteriovenous malformation, intracerebral arteriovenous malformation, bilateral glomus tumours, systemic lupus erythematosus, Wegener's granulomatosis, non-Hodgkin's lymphoma. The recognition of such diverse aetiology may be importance since clinical features are non-specific, and may consist only of raised intracranial pressure, allowing confusion with 'benign intracranial hypertension'. The existence of effective treatment both for the thrombosis and for many of the underlying disorders makes early diagnosis essential. The prognosis of treated patients may be favourable.
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PMID:Cerebral venous thrombosis: new causes for an old syndrome? 214 67

In order to define the behavior of the lupus anticoagulant and/or antiphospholipid antibodies, we investigated the possible association with protein C, protein S and thrombomodulin. In 19 patients with established diagnosis of an autoimmune disease and coexisting lupus anticoagulant protein C (antigen and activity), protein S (total and free), anticardiolipin and antiphosphatidylserine antibodies were estimated. In one case the IgG globulin fraction containing the inhibitor was separated. The activation rate of pure protein C to its activated form using thrombin/thrombomodulin as activator was then measured in the presence or absence of lupus anticoagulant. No overall decrease of protein C or protein S was detected in patients' plasma. Nevertheless, the lupus anticoagulant had a specific effect on the protein C system, inhibiting the catalytic activity of thrombomodulin without causing a functional protein C deficiency. This specific effect upon thrombomodulin can be a main cause, but not necessarily the only one, for the thrombophilic tendency of patients with the lupus anticoagulant.
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PMID:Lupus anticoagulant--antiphospholipid antibodies and thrombophilia. Relation to protein C--protein S--thrombomodulin. 216 70

In this review paper, the salient features of the anticoagulant/fibrinolytic mechanism depending on coagulation protein C, protein S and thrombomodulin are reviewed. Coagulation protein C, activated at the endothelial cell surface in the presence of the complex thrombin/thrombomodulin exerts two anti-thrombotic effects: one anticoagulant dependent on the free protein S and the other pro-fibrinolytic, independent of protein S. Both inherited and acquired deficiencies of protein C and/or protein S lead to a thrombosis-prone state that has to be identified promptly to avoid vaso-occlusive episodes. The experience in Mexico with both the identification and treatment of these deficiencies is reviewed; it is interesting that we have found that patients with autoimmune disorders, mainly systemic lupus erythematosus and primary anti-phospholipid syndrome, have acquired deficiencies of this anticoagulant mechanism that may be related to the thrombogenesis observed in these patients.
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PMID:[Protein C, protein S and thrombomodulin: one of the natural antithrombotic mechanisms]. 217 90

Components of the natural anticoagulant system (NAS) and anticardiolipin antibodies were examined in 21 patients with lupus anticoagulant (LA), 13 of whom had past histories of thrombotic episodes. No relationship could be shown between the antigenic levels of protein C and S (PC, PS) and a history of thrombosis. Inhibition of the anticoagulant activity of activated protein C (APC) was observed using plasma from 20/21 patients when phospholipid vesicles were used as the surface for the coagulation reaction. This effect was not affected by the addition of PS. When platelet membranes were employed only 2/21 patients demonstrated inhibition of APC. Under the latter condition, PS functional activity was inhibited in 7/21 patients, six of whom had a past history of thrombosis. Reduced antithrombin III or heparin cofactor II levels were observed in a total of 4/21 patients and may have contributed to the development of thrombosis in three of these patients. Antibodies specifically directed against these proteins were not detected suggesting the possibility of an associated constitutional deficiency. Anticardiolipin antibodies, though elevated in 17/21 patients, did not serve as a useful marker for an increased risk of thrombosis, and the level did not correlate with inhibition of the activity of APC or PS. We conclude that the mechanism of thrombosis in patients with LA is multi-factorial. A subset of patients in whom LA specifically inhibits PS function may represent patients who are at significant risk from thrombosis.
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PMID:Studies of natural anticoagulant proteins and anticardiolipin antibodies in patients with the lupus anticoagulant. 217 38


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