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)

Antibodies that bind prothrombin without neutralizing its coagulant activity were demonstrated in the plasma of two patients with the acquired hypoprothrombinemia-lupus anticoagulant syndrome. The first patient's plasma contained less than 1% prothrombin activity and no detectable prothrombin antigen. The second patient's plasma contained about 6% of both prothrombin activity and antigen. Neither patient's plasma neutralized the prothrombin coagulant activity of normal plasma or of purified prothrombin added in vitro. Nevertheless, double immunodiffusion studies and binding experiments utilizing 125I-prothrombin demonstrated the presence of prothrombin antibodies in each patient's plasma. A Scatchard analysis of the binding data obtained with different concentrations of 125I-prothrombin and the first patient's plasma indicated the presence of a high affinity antibody, apparent Kd approximately 10(-10)M, and a lower affinity antibody, apparent Kd approximately 10(-9)M. Studies utilizing purified cleavage products of prothrombin suggested that the antibodies were directed against an epitope or epitopes located on the carboxyl-terminal, latent thrombin segment of the prothrombin molecule. We postulate that the acquired hypoprothrombinemia in these two patients and in other reported patients with the acquired hypoprothrombinemia-lupus anticoagulant syndrome stems from rapid clearance from the circulation of prothrombin antigen-antibody complexes.
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PMID:A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome. 640 77

Lupus anticoagulant is an immunoglobulin that interferes with prothrombin conversion to thrombin and is manifested biochemically by prolongation of the partial thromboplastin time. Paradoxically, bleeding is rare in association with this anticoagulant, and deep leg vein thromboses, pulmonary emboli, and cerebrovascular accidents have been described in patients with this clotting inhibitor. This report describes the first case of Budd-Chiari syndrome associated with the lupus anticoagulant. The patient presented with abdominal pain and massive ascites. The Budd-Chiari syndrome was confirmed by liver biopsy and venography. No medical condition known to predispose to an increased thrombotic tendency could be identified, and the presence of the lupus anticoagulant in the patient's plasma may provide an explanation for his hypercoagulability and development of the Budd-Chiari syndrome.
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PMID:Budd-Chiari syndrome in a patient with the lupus anticoagulant. 641 18

Plasmas from ten patients with a lupus or lupus-like inhibitor were investigated. In each case the partial thromboplastin time with kaolin (PTTK) was prolonged and failed to correct on the addition of an equal volume of normal plasma. Activated control platelets corrected the inhibitory effect in the PTTK or thrombin generation time (TGT) in every instance. Activated autologous platelets were as effective as control platelets and may thus explain why bleeding is rarely associated with the lupus inhibitor. Experiments using platelets or plasma from patients congenitally deficient in a single clotting factor or normal washed platelets resuspended in deficient plasma indicated that the inhibitor by-passing activity is platelet and not plasma derived. Platelet fractionation studies suggested that this activity is localised at the platelet membrane.
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PMID:Investigations of the lupus-like inhibitor by-passing activity of platelets. 642 Sep 22

Plasma antithrombin III (AT III) was studied in 39 patients with systemic lupus erythematosus (SLE) and in 12 patients with other connective tissue disorders. AT III was measured immunologically by the Mancini method as well as by functional assay using thrombin and the chromogenic substrate, chromozyn TH (Boehringer). Reduced AT III activity was found in 17 patients; 8 had thrombosis. In 6 patients low AT III correlated with disease exacerbations and 2 had systemic vasculitis. No significant correlation could be demonstrated between low AT III levels and thromboembolic disease. A marked variation of functional AT III activity was observed in 30 patients in whom the presence of the lupus anticoagulant was demonstrated. The significance of this association is discussed.
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PMID:Antithrombin III in systemic lupus erythematosus. 644 39

A case is reported of a young female patient with a circulating lupus anticoagulant. The illness, associated with several spontaneous abortions, is characterized as a "Soulier and Boffa syndrome". No severe bleeding occurred when she underwent several major operations. The clinical picture of lupus anticoagulant is discussed, as well as the perioperative management of such patients. The presence of a lupus anticoagulant, if not associated with other hemostatic defects, is not a contraindication to surgery. The risks and benefits of postoperative heparinization are recalled. Thrombin time seems to be the best coagulation test for adapting heparin doses.
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PMID:[Surgery and circulating antiprothrombinase-type anticoagulant in the Soulier-Boffa syndrome]. 654 Oct 9

We have investigated the effects of plasma and serum from normal subjects on the production of prostacyclin (PGI2) by cultured porcine aortic vascular endothelial cells, measured by radioimmunoassay of its stable metabolite 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha). Both plasma and serum caused significant stimulation of the production of 6-keto PGF1 alpha over basal levels. Serum caused consistently greater stimulation than plasma from the same individual. Washed platelet suspensions were induced to aggregate using thrombin and the supernatants stimulated the production of 6-keto PGF1 alpha by cultured endothelial cells. Preliminary studies also show that a stimulatory factor is released from cultured human leucocytes. Serum from patients with systemic lupus erythematosus (SLE) and severe systemic sclerosis (SS), two connective tissue diseases with autoimmune features and vascular complications, showed significantly reduced levels of stimulation when compared with a control group.
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PMID:Stimulation of prostacyclin production from vascular endothelial cells by plasma, serum and platelets under normal and pathological conditions. 675 53

Native (n) but not single stranded (ss) DNA was found to induce release of 3H-serotonin (5-HT) from platelets of the majority of normal individuals. However, ssDNA markedly enhanced 5-HT release induced by heat-aggregated IgG (aggIgG), while less enhancement was seen using nDNA. Similar enhancement was produced by polyinosinic acid but not by polyinosinic:polycytidylic acid. The ability of ssDNA to potentiate aggIgG-induced 5-HT release seemed specific for aggIgG, since no effect on ADP or epinephrine-induced release was observed and thrombin-induced release was inhibited. In contrast, nDNA in high concentrations (100 micrograms/ml) potentiated ADP, epinephrine, and thrombin-induced 5-HT release. These results suggest that ss-and nDNA may interact with platelets by different mechanisms and provide a means by which DNA, released at sites of tissue injury, could modulate the role of platelets in the inflammatory response. The ability of DNA to enhance the aggIgG-induced platelet release reaction may be important in immune complex diseases such as systemic lupus erythematosus.
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PMID:The effect of native and single stranded DNA on the platelet release reaction. Enhancement of aggregated IgG-induced serotonin release. 682 15

An acquired platelet functional defect was found to be present in eight patients who presented with various clinical conditions--three with renal allograft rejection, three with the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, one with acute consumption coagulopathy due to an incompatible transfusion and one with systemic lupus erythematosus. They showed defective platelet aggregation and reduced levels of adenine nucleotides and serotonin with abnormal uptake and storage of the amine. The bleeding time was more prolonged than predicted from the platelet count. These abnormalities were strikingly similar to those occurring in patients with congenital storage pool deficiency. The acquired defect is thought to be related to the presence in the circulation of "exhausted" platelets following their in vivo exposure to inducers of the release reaction such as damaged endothelium, thrombin and immune complexes. The bleeding tendency of the underlying diseases might be aggravated by the impairment of platelet function.
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PMID:Acquired dysfunction due to the circulation of "exhausted" platelets. 740 45

In order to determine whether there is a relationship between acquired free protein S deficiency and increased thrombin generation, we performed a cross-sectional study of patients with systemic lupus erythematosus (SLE). Plasma samples were assayed for free protein S and were correlated to levels of prothrombin fragments (F1 + 2); an elevated level of F1 + 2 was used as a surrogate marker for a prothrombotic state. Assays for anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) were performed on two separate blood samples taken at least 3 months apart in order to detect the presence of antiphospholipid antibodies. Of the 36 subjects, 9 had reduced free protein S levels compared to 0 of 21 controls (P = 0.01) and the mean free protein S level was significantly lower in the SLE population than in controls (0.30 +/- 0.08 U/mL versus 0.43 +/- 0.10 U/mL, P < 0.001). Of the 24 subjects with antiphospholipid antibodies, 9 had reduced free protein S levels, compared to 0 of 12 subjects without antiphospholipid antibodies (P = .01). The mean F1 + 2 level was significantly higher in study subjects with reduced free protein S levels than in those with normal free protein S levels (1.22 +/- 0.50 nmol/L versus 0.78 +/- 0.27 nmol/L, P = 0.05). This study confirms an association between antiphospholipid antibodies and reduced free protein S levels and demonstrates that patients with SLE and acquired free protein S deficiency generate more thrombin than patients with SLE and normal free protein S levels. Further studies are needed to determine whether the thrombotic diathesis associated with the presence of antiphospholipid antibodies is directly caused by the concomitant presence of acquired free protein S deficiency.
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PMID:Acquired free protein S deficiency is associated with antiphospholipid antibodies and increased thrombin generation in patients with systemic lupus erythematosus. 770 51

The venom of P. textilis contains two different enzymes which convert human prothrombin into thrombin. Prothrombin activation by Textarin, a serine proteinase containing a calcium-binding molecule site, with a molecular mass of 50,000 to 53,000 Da and I.P. 5.5, separated from crude venom by either barium citrate adsorption or hydroxyl apatite chromatography, is strongly stimulated by phospholipid and calcium ions. A second activator, found in the supernatant of barium citrate adsorbed venom solution, activates prothrombin in the absence of any co-factor. Human plasma coagulation induced by Textarin, phospholipid and calcium ions is affected by lupus anticoagulants. Textarin may thus be used for the detection of lupus anticoagulants in patient plasma samples.
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PMID:Isolation and characterization of Textarin, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom. 784 93


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