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)

Two patients with well documented systemic lupus erythematosus developed a syndrome resembling thrombotic thrombocytopenic purpura. Both had severe thrombocytopenia, microangiopathic hemolytic anemia, seizures, and renal dysfunction. Prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen levels were normal; fibrin degradation products were minimally elevated. Histologic evaluation of renal biopsies in both patients confirmed the impression of intravascular thrombosis. Therapy with corticosteroids, other immunosuppressive drugs and splenectomy (in one case) proved unsuccessful. The infusion of fresh frozen plasma, with or without plasmapheresis, reversed the syndrome. This report indicates that patients with systemic lupus may develop a thrombotic thrombocytopenic purpura like syndrome which responds to fresh plasma infusion.
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PMID:Thrombotic thrombocytopenic purpura syndrome in systemic lupus erythematosus: treatment with plasma infusion. 404 Nov 34

The platelet binding properties of human monoclonal lupus autoantibodies have been studied. These IgM autoantibodies, produced by human X human hybridomas derived from lymphocytes of patients with systemic lupus erythematosus, are known to bind to single-stranded DNA. Four anti-DNA antibodies that express the dominant 16/6 idiotype--HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6--bound to glutaraldehyde-fixed platelets. In contrast, HF6-21/28, HF9-11/3, and polyclonal IgM bound poorly to platelets. [35S]Methionine was incorporated into HF2-1/17, and the interaction of the intrinsically radiolabeled HF2-1/17 with fixed platelets was evaluated in a solution phase radioimmunoassay. [35S]Methionine HF2-1/17 bound to fixed platelets and could be displaced by equivalent amounts of HF2-1/17, HF2-18/2, HF2-1/13b, and HF3-16/6. HF2-1/17 bound with greater affinity to fresh platelets and to thrombin-activated platelets than to glutaraldehyde-fixed platelets. Single-stranded DNA competed with platelets for the HF2-1/17 combining site. Treatment of fresh platelets with nuclease I, trypsin, chymotrypsin, and neuraminidase did not alter the binding of antibody to the platelet surface. No binding of antibody to phospholipid micelles was observed. Purified IgM autoantibodies did not inhibit platelet aggregation induced with ADP, thrombin, or ristocetin in platelet-rich plasma. These results indicate that the human IgM monoclonal anti-DNA autoantibodies that express the dominant 16/6 idiotype are polyspecific, bind to platelets, and interact with a platelet epitope that does not appear to involve DNA, protein, or sialic acid. These antibodies interact with platelets through the same sites responsible for antibody-DNA binding.
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PMID:Platelet binding properties of monoclonal lupus autoantibodies produced by human hybridomas. 406 19

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

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

Resistance to activated protein C (RAPC) has been described recently as a cause of trombophilia; this may justify up to 50% of thromboembolic disease without predisposing cause in patients under 45 years. A 29 years-old male with a previous deep venous thrombosis (DVT) in the lower left limb three years earlier, developed a DVT in the right lower limb after a trauma of the knee that required immobilization, was associated to pulmonary thromboembolism diagnosed by gammagraphic methods. The phlebographic study showed femoro-iliaco-caval venous thrombosis. The proband's father and a younger brother had a previous history of thrombotic episodes. The following tests, were performed in the proband and relatives: prothrombin time, aPTT, thrombin time, fibrinogen, (Von Clauss), antithrombin III (chromogenic), protein C and protein S (coagulometry and ELISA), plasminogen (chromogenic) and lupus anticoagulant (ITT, dRVVT, aCL). RAPC was evaluated in two different samples. The proband study was performed under oral anticoagulation treatment (OAT). Control groups were: 21 blood donors and 12 OAT patients. The results showed a decreased response to APC in the proband (ratio 1.5) and relatives: father (1.4), brothers (1.5 and 1.5), while the mother was within the normal range (> or = 2). In normal controls and OAT patients the ratio was over 2. No other abnormalities were detected in the assays performed. It is concluded that RAPC is the cause of this familial trombophilia. RAPC should be included in the evaluation study of trombophilia.
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PMID:[Familial thrombophilia due to resistance to activated protein C]. 798 58


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