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)

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

The lupus anticoagulant is an antiphospholipid antibody found in association with systemic lupus erythematosus and in a variety of other diseases, as well as in healthy individuals. In the laboratory, the antibody interferes with the conversion of prothrombin to thrombin and prolongs the partial thromboplastin time. In vivo, it exerts a procoagulant effect resulting in thrombosis, mainly of the larger veins and arteries. The case of a young woman who developed superficial migratory thrombophlebitis in association with a high titer lupus anticoagulant is presented. Her diagnosis was initially missed because the partial thromboplastin time was not elevated. This appears to have resulted from the use of a specific thromboplastin relatively insensitive to the presence of the antibody. Retesting with a more sensitive reagent showed a markedly prolonged partial thromboplastin time.
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PMID:Superficial migratory thrombophlebitis and the lupus anticoagulant. 211 May 53

To clarify the pathogenesis of antiphospholipid antibody (aPL) syndrome, the reactivities of anticardiolipin antibodies (aCL) in sera of patients with systemic lupus erythematosus (SLE) or other diseases to fresh, activated or destroyed blood cells were examined by the inhibition assay using an enzyme-linked immunosorbent assay. In addition, the effects of lupus anticoagulants (LA) in the patients' plasma and of immune complexes formed between LA and PL antigens on platelet aggregations were also determined. The IgG-aCL activity of patients' sera was markedly inhibited by pre-incubation with freeze-thawed blood cells, including erythrocytes (RBC), mononuclear cells (MNC) and platelets, but not fresh platelets or RBC. The aCL activity was slightly inhibited by fresh MNC, and was definitely inhibited by thrombin-activated platelets and polymorphonuclear cells (PMN) stimulated with phorbol 12-myristate 13-acetate (PMA). However, the activity was not inhibited by platelets stimulated with adenosine 5'-diphosphate (ADP; 10 microM). Twenty-two LA positive plasma and 17 LA negative plasma from patients similarly enhanced the aggregation of platelets which were obtained from healthy adults and stimulated with low concentrations of ADP (1 or 2 microM). However, such enhancement of platelet aggregation was not observed when high concentrations of ADP (5 microM) or collagen (2 micrograms/ml) were used as stimulators. In four of the 16 LA positive plasma examined, the mixture of plasma and phospholipid reagent for activated partial thromboplastin time induced platelet aggregations without the other stimulations, but the plasmas themselves did not induce such a reaction. The above results indicate that the aPL from patients do not react with intact blood cells in vitro, but they can react with activated or destroyed blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactivities of antiphospholipid antibodies to blood cells and their effects on platelet aggregations in vitro. 212 28

Platelets play a central role in haemostasis. Not only are they involved in aggregatory and agglutination responses but they are also implicated in the clotting system. The conversion of prothrombin to thrombin, in the presence of coagulation factors Va, Xa and calcium ions, is termed prothrombinase activity. For optimal expression of this process a negatively charged phospholipid surface is required. Platelets can provide such an environment, by exposing negatively charged phospholipids at their external plasma membrane, by a 'flip-flop' process whereby negatively charged phospholipids, predominantly phosphatidylserine, move from the inner plasma membrane leaflet to the outer leaflet upon the activation of platelets by certain agonists. Such agonists include collagen and thrombin and the amount of prothrombinase activity expressed is well correlated with the propensity of the agonist to activate platelet calcium-dependent protease, calpain. This enzyme is then thought to act upon platelet cytoskeletal components, thus breaking the restraining action of the cytoskeleton upon the platelet plasma membrane and facilitating 'flip-flop'. The platelet plasma membrane is therefore a dynamic surface capable of catalytic functions in coagulation systems. Recent research has high-lighted abnormalities in platelet prothrombinase expression in certain disease states. These include Bernard-Soulier syndrome, essential thrombocythaemia and conditions where the lupus anticoagulant may be present.
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PMID:Platelet prothrombinase in health and disease. 213 Sep 28

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

A 37-year-old intravenous drug abuser with acquired immune deficiency syndrome showed elevated activated partial thromboplastin time (APTT) and prothrombin time, normal thrombin time and fibrinogen, and borderline low platelet counts. The patient subsequently had a fracture of the left zygomatic arch, which did not produce uncontrollable bleeding. The coagulogram repeated at this admission showed persistent elevation of APTT. Further coagulation workup showed the presence of a lupus anticoagulant with mild specific inhibition of Factor VII. Platelet aggregation and Factor II levels were normal.
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PMID:Lupus anticoagulant associated with specific inhibition of factor VII in a patient with AIDS. 249 80

A patient with microvascular thrombosis and thrombocytopenia was found to have a high-titre lupus anticoagulant. The biological effects of the patient's lupus anticoagulant were studied using whole patient serum and plasma. Staph Protein A eluate, and affinity-purified lupus anticoagulant. The latter was isolated by immunoadsorption of serum onto cardiolipin/phosphatidylserine/cholesterol liposomes. Each source of lupus anticoagulant demonstrated 'anticoagulant' activity, defined as prolongation of a modified kaolin clotting time, and contained antibody which bound to endothelial monolayers. Each interfered with thrombin-mediated prostacyclin release from endothelial cells, but had no effect on arachidonate-induced prostacyclin release. In addition, the lupus anticoagulant selectively blocked platelet aggregation in response to thrombin, but not in response to arachidonate, ADP or epinephrine. Lupus anticoagulant also reduced thrombin-stimulated shifts in cytosolic calcium. Thrombin-mediated membrane inositol metabolism and total thrombin binding to endothelium were unaffected by lupus anticoagulant, and another endothelial anticoagulant function related thrombin binding. Protein C activation by thrombomodulin, was not altered. We conclude that the binding of lupus anticoagulant to endothelial cells and platelets does not prevent all thrombin signalling events, but does interrupt prostacyclin production.
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PMID:Lupus anticoagulant induces a selective defect in thrombin-mediated endothelial prostacyclin release and platelet aggregation. 249 19

We studied the effects of heparin, dextran sulphate (MDS), gabexate mesilate (FOY), nafamostat mesilate (FUT-175) and argipidine (MD-805) on APTT, PT, thrombin time (TT) and kaolin-activated PTT (KPTT) with various concentrations of phospholipid for screening of lupus anticoagulants (LA). Heparin, MDS and FUT-175 had a greater effect on APTT than PT. On the contrary, MD-805 had a similar effect on both APTT and PT, which suggests that MD-805 inhibits thrombin generation equally on intrinsic and extrinsic coagulation pathways. Heparin and MD-805 were more effective on TT than MDS, FUT-175 and FOY at high concentrations significantly prolonged TT. But, at even higher concentrations of FUT-175, prolongation of TT was reduced contrary to our expectation. With FOY TT became less prolonged with a passage of time, suggesting time-dependent reduction of its anticoagulant activity. Heparin (0.1-0.2 U/ml) and MDS (0.1-0.3 mg/ml) did not have any effect on KPTT with high concentration of phospholipid, but did FUT-175. It suggests that phospholipid inhibits anticoagulant activity of heparin and MDS. Anti-phospholipid activity of heparin and MDS is similar to that of LA. We concluded that the differentiation of LA from heparin-like inhibitors is needed.
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PMID:[The effects of various anticoagulants on blood coagulation: with special reference to false positive lupus anticoagulants]. 251 25

One hundred and fifty-seven HIV seropositive patients were included in a prospective study of coagulation parameters. Activated partial thromboplastin time, prothrombin time, thrombin time and specific factor assays of the intrinsic pathway were performed using standard techniques. The tissue thromboplastin inhibition test and antiphospholipid antibodies were used to establish the presence of circulating lupus anticoagulant. Among the 46 patients with a prolonged activated partial thromboplastin time, an anti-prothrombinase was present in 33. Of the 111 patients with a normal activated partial thromboplastin time, anti-prothrombinase was present in 51. Circulating lupus anticoagulant seems to be common in HIV seropositive patients, since it was found in 84 patients (53.5%). Our findings confirm that the presence of circulating anticoagulants is not particularly associated with opportunistic infections or the development of the disease. It is possible that these inhibitors could be mediated by anti-phospholipid antibodies. In HIV seropositive patients, defective T cell regulation of B cells leads to polyclonal hypergammaglobulinemia. These antibodies may be directed against endogenous or exogenous phospholipids.
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PMID:[Circulating anticoagulants in immunodeficiency virus infection. Results of a prospective study of 157 seropositive patients]. 259 85


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