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)

A 51 year-old man with a history of deep venous thromboses and recurrent pulmonary embolism on long-term anticoagulant treatment was admitted to our department because of insidious onset thrombocytopenia. He had neither a history nor clinical signs of abnormal bleeding. On admission, the platelet count was reduced to 21 x 10(9)/l, platelet associated IgG was increased, and bone marrow specimens showed megakaryocytic hyperplasia. Platelet survival was slightly shortened with enhanced platelet sequestration in a normal size spleen. Laboratory evaluation after discontinuation of anticoagulant treatment revealed persisting prolongation of both the prothrombin time and the activated partial thromboplastin time which could be attributed to the presence of a lupus-type circulating anticoagulant. Further relevant laboratory findings included an elevated titer of IgG anti-cardiolipin antibodies and a reduced euglobulin clot lysis activity after venous occlusion due to increased plasminogen activator inhibitor activity. In recent years, it has become apparent that a striking correlation exists between the presence of antibodies to phospholipids and thromboembolic disease and immune thrombocytopenia respectively. The present case report on the association of these autoantibodies with both, recurrent venous thromboembolism and severe thrombocytopenia, supports the hypothesis that anti-phospholipid antibodies may play a crucial part in the pathogenesis of these clinical conditions. A reduced vascular fibrinolytic capacity may be involved in the thrombophilic state induced by anti-phospholipid antibodies.
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PMID:[Anti-phospholipid antibody with recurrent venous thromboembolism and severe autoimmune thrombocytopenia]. 250 50

Lupus anticoagulant, concentrations of anticardiolipin antibodies, antithrombin III, plasminogen, (free) protein S, protein C, prothrombin, platelet counts, and bleeding times were determined in 74 lupus patients (58 with systemic lupus erythematosus; 16 with lupus-like disease) to establish the presence of risk factors for thrombosis in these patients. Of the variables evaluated, lupus anticoagulant had the strongest association with a history of thrombosis. Both positive anticardiolipin antibody concentrations and the presence of (mild) thrombocytopenia were significantly associated with a history of thrombosis and the presence of lupus anticoagulant. Reduced concentrations of antithrombin III, plasminogen, (free) protein S, and protein C were found in some patients but were not associated with either thrombosis or lupus anticoagulant. Mean concentrations of total protein S were significantly lower in patients with thrombosis than in those without and in patients with lupus anticoagulant than in those without. The antigenic concentration of prothrombin was reduced in 3/74 (4%) lupus patients. These three patients had lupus anticoagulant but no history of thrombosis, which suggests that a low prothrombin concentration protects patients with lupus anticoagulant from the development of thrombosis. A prolonged bleeding time was associated with the presence of lupus anticoagulant but not with a history of thrombosis. Analysis by stepwise logistic regression did not disclose additional risk factors for thrombosis in lupus patients with lupus anticoagulant. Increased antithrombin III concentrations and decreased free protein S concentrations are often found in lupus patients, unrelated to lupus anticoagulant or thrombosis.
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PMID:Risk factors for thrombosis in lupus patients. 251 63

Anti-phospholipids represent a heterogeneous family of antibodies able to react with the negatively charged phosphodiester groups of phospholipids. It includes the antibodies directed against the cardiolipin moiety of the VDRL antigen, the antibodies reacting with the phospholipids of the prothrombin activator complex and the antibodies able to react with solid phase cardiolipin. Data are reported indicating that reagins share distinct characteristics in comparison to the autoimmune anti-cardiolipin antibodies (ACA). On the contrary anti-phospholipid antibodies responsible for lupus-like anticoagulant activity display a quite similar reactivity with ACA, even if a complete overlapping cannot be demonstrated. The relationships between ACA and anti-DNA antibodies are also reported. The biological and clinical significance of these crossreactivities are discussed.
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PMID:The pathophysiology of anti-phospholipid antibodies. 251 60

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

Coagulation profile was studied in 55 patients of systemic lupus erythematosus (SLE). Abnormal kaolin clotting time (KCT) was observed in fewer patients (12.9%) as compared to abnormal Russel's viper venom time (RVVT, 20.4%) or activated partial thromboplastin time (APTT, 32.7%). Prolonged prothrombin time (PT), observed in 7.3 per cent patients was not found to be a sensitive test for lupus anticoagulant (LAC). The correction of RVVT and KCT on addition of inosithin suggested a deficiency of platelet lipid factor in these patients. The initial value of uncorrected KCT in patient's plasma did not correlate with the amount of inosithin required for neutralisation. Occurrence of thromboembolic events was significantly associated with prolonged KCT. No other clinical feature showed significant association with any coagulation abnormality.
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PMID:Coagulation abnormalities in systemic lupus erythematosus. 262 1

Most causes of abnormal bleeding can be determined from a complete blood count including platelet count and bleeding, prothrombin, activated partial thromboplastin, and thrombin times. Occasionally, further evaluation is necessary, such as tests of factor XIII function, fibrinolysis, and vascular integrity. Possible diagnoses include disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, vitamin K deficiency, von Willebrand's disease, heparin-induced thrombocytopenia, acquired inhibitors of factor VIII, lupus anticoagulants, and coagulation disorders related to the acquired immunodeficiency syndrome.
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PMID:Laboratory evaluation of a bleeding patient. 266 Apr 7

Abnormal coagulation profiles were identified in ten patients with the acquired immunodeficiency syndrome (AIDS) associated with opportunistic infections and malignancies. Activated partial thromboplastin times were elevated in all patients; three of seven had elevated prothrombin times. All patients had lupus-type anticoagulants characterized by rapid prolongations of the partial thromboplastin time in mixing studies, prolonged dilute thromboplastin inhibition assays, and increased Russell viper venom clotting times. Ivy bleeding times were prolonged in three patients with defective platelet aggregation. The lupus anticoagulant was isolated from the sera of healthy heterosexual men and from patients with AIDS with and without the lupus anticoagulant, and in the presence and absence of opportunistic infections. Both polyclonal IgM and IgG lambda from plasma with lupus anticoagulant interfered with clotting studies and platelet aggregation. The inhibitors usually accompanied active opportunistic infections and tended to disappear with successful resolution of infection.
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PMID:Circulating coagulation inhibitors in the acquired immunodeficiency syndrome. 308 Sep 33

In a prospective study assessing haemostatic functions, the activated partial thromboplastin time was prolonged in 134 out of 10,229 patients studied, without an increase in the prothrombin or thrombin times; this abnormality persisted in only 37 of them on a new blood sample. A retrospective analysis was made of 265 patients who had such an isolated prolongation of the activated partial thromboplastin time on two successive blood samples: the causal abnormality remained unexplained in 135 patients; a well defined coagulation disorder without abnormal bleeding tendency was present in 110 patients (1 severe factor XII deficiency, 58 partial factor XI or XII deficiencies and 51 lupus anticoagulants); a bleeding disorder was diagnosed in 20 patients (8 haemophilias, 8 Von Willebrand's diseases, 4 factor VIII inhibitors). The well-iron efficacy of the activated partial thromboplastin time for detecting coagulation abnormalities is counter-balanced by some disadvantages such as the delay for biologic conclusions. In the preoperative assessment of haemostatic functions, rather than taking a routine approach, it would seem better to determine for each patient the need and the extent of biological testing according to the type of planned surgery, the clinical status of the patient and possible bleeding symptoms.
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PMID:[Successes and failures of the activated partial thromboplastin time in the preoperative evaluation]. 308 57

The lupus anticoagulant (LA) is an acquired autoantibody of the IgG or IgM type that acts on platelet factor III, inhibiting the generation of the prothrombin activator complex. It is prevalent in 5-10% of SLE cases and, in contradistinction to the name anticoagulant, it may be associated with thrombotic events, recurrent abortion or intrauterine death. Anti-cardiolipin antibody like LA, is an anti-phospholipid antibody and also causes recurrent thrombotic events. Mention has been made of a possible cross-reactivity between anti-phospholipid antibodies and anti-DNA antibodies. The optimal treatment for this problem is at present unknown.
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PMID:Lupus anticoagulant and anticardiolipin antibodies in systemic lupus erythematosus. 310 68

Although observations have implied that lupus anticoagulants have immunologic specificity toward anionic phospholipids, this assumption has been directly demonstrated in only one patient with a monoclonal IgM paraprotein. We tested the generality of this hypothesis directly by isolating five IgG lupus anticoagulants from patients with lupuslike syndromes and/or thrombosis. IgG lupus anticoagulant fractions were isolated free of other plasma proteins and free of contaminating phospholipid by adsorption to and elution from cardiolipin-cholesterol-dicetyl phosphate liposomes, followed by chromatography on protein A-Sepharose. Cardiolipin liposomes, but not phosphatidylcholine liposomes, were capable of removing all, or nearly all, lupus anticoagulant activity from patient plasma. The affinity-purified IgG preparations reacted with cardiolipin, phosphatidylserine, phosphatidylinositol, and phosphatidic acid, but not with phosphatidylcholine or phosphatidylethanolamine, and inhibited calcium-dependent binding of prothrombin and of factor X to phosphatidylserine-coated and to cardiolipin-coated surfaces. F(ab')2 fragments retained lupus anticoagulant activity and bound to cardiolipin in an enzyme-linked immunosorbent assay (ELISA). Anticardiolipin and lupus anticoagulant activity were both present in acidic fractions on isoelectric focusing. These data strongly suggest that most, if not all, lupus anticoagulants are antibodies that have immunologic specificity towards anionic phospholipids, thereby blocking the calcium-mediated binding of vitamin K-dependent coagulation factors to coagulation-active phospholipid surfaces.
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PMID:Immunological specificity and mechanism of action of IgG lupus anticoagulants. 310 26


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