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)

Much evidences have been accumulated that antiphospholipid antibodies (aPL), especially anticardiolipin antibodies (aCL) and lupus anticoagulant (LA), were associated with thromboembolism, recurrent fetal loss and thrombocytopenia. These patients with clinical manifestations and aPL are classified into antiphospholipid syndrome (APS). Patients with APS without known well-defined autoimmune diseases are assigned to primary APS. aCL found in sera from patients with the APS recognize epitope(s) on beta 2-glycoprotein I bound to cardiolipin. LA is bound to the complex of prothrombin and anionic phospholipids. Patients with APS can be treated by low dose aspirin, warfarin or heparin. A few patients with aPL develop an acute and multiple organ involvements of APS. These patients are designated as catastrophic APS and are treated intensively by corticosteroid, immunosuppression, plasmapheresis or streptokinase.
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PMID:[Current topics in vascular disorders]. 793 3

The dilute prothrombin time (dPT) is a widely accepted sensitive screening test for the lupus anticoagulant (LA). In general, Simplastin (Organon Teknika), a rabbit brain thromboplastin, diluted 1/500, is used in this test. Recently, human tissue thromboplastin obtained by recombinant DNA technology has become available and we have evaluated the usefulness of one such preparation, Innovin (Dade), for the detection of the LA. dPTs, using several dilutions of Innovin were determined on plasmas from 18 normal individuals and 15 patients with a well-documented LA. The dPT ratios, calculated as the individual result divided by the mean normal, were statistically compared. Innovin in dilutions from 1/100 onwards was found to be significantly more responsive to the LA than Simplastin (P < 0.05). Intra-assay coefficients of variation (CVs) ranged from 1.05% to 14.8% with Innovin, versus 2.7%-24.3% with Simplastin (P < 0.05); inter-assay CVs ranged from 5.6%-11.8% with Innovin, versus 4.2%-33.8% with Simplastin (P < 0.001). Analysis of 316 consecutive plasma samples from non-anticoagulated patients, on which a LA determination was requested, showed a 100% sensitivity and a 96% specificity of the dPT performed with Innovin, as compared to 81% and 93% respectively for the dPT using Simplastin.
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PMID:Optimization of the dilute prothrombin time for the detection of the lupus anticoagulant by use of a recombinant tissue thromboplastin. 794 61

Three children with systemic lupus erythematosus who developed hemorrhagic tendencies as a consequence of a clotting factor II (prothrombin) deficiency are described. All three responded rapidly to treatment with corticosteroids. A literature review added 25 case reports, with the following findings. First, factor II deficiency occurs in the presence of the lupus anticoagulant, although the interrelationship between the two is not understood. Second, the deficiency is presumed to be secondary to rapid clearing of the antigen/antibody factor II complex in the liver. Finally, most cases respond to corticosteroid therapy with or without the coadministration of vitamin K or fresh frozen plasma. In corticosteroid-dependent patients, the addition of antimetabolites such as azathioprine has enabled reduction in steroid doses.
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PMID:Hypoprothrombinemia in childhood systemic lupus erythematosus. 798 33

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

Lupus anticoagulants, commonly found in the immunoglobulin fraction of patients with the antiphospholipid syndrome (APS), and the normal plasma protein beta 2-glycoprotein 1 (beta 2GP1) may both contribute to the in vitro impairment of prothrombin activation associated with the APS. We examined the effects upon prothrombin activation supported by phospholipid vesicles of plasma IgG preparations from APS patients in the presence and absence of beta 2GP1. Using a purified system for measurement of prothrombin activation to thrombin, we demonstrated significant phospholipid concentration-dependent inhibition of prothrombin activation in the absence of beta 2GP1 by 11 consecutive patient IgG preparations. The degree of inhibition of prothrombin activation by equivalent concentrations of patient IgG correlated well with the extent of prolongation of the plasma clotting time in lupus anticoagulant assays of whole patient plasma. Additional studies with eight patient IgG preparations indicated that the addition of beta 2GP1 to patient IgG-phospholipid vesicle mixtures resulted in either independently additive inhibition by the two protein species (six cases) or potential inhibition of beta 2GP1 of the IgG inhibitory activity demonstrable in the absence of beta 2 GP1 (two cases). In addition, beta 2GP1-independent inhibition of prothrombin activation also occurred with three patient IgG preparations obtained by affinity binding to cardiolipin.
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PMID:Inhibition of prothrombin activation by antiphospholipid antibodies and beta 2-glycoprotein 1. 799 95

The authors define pro-thrombotic states as conditions associated with a high frequency of thrombosis; this association is based on pathogenetic or simply clinical and epidemiological relationships. Thrombophilic states have well-defined, specific causes: antithrombin III, protein C and S and similar deficiencies for inherited thrombophilias, and lupus anticoagulant, antiphospholipid antibodies for the acquired forms. Another identifiable group is made up of several conditions predisposing to thrombosis (CPT) characterized by less specific and multiple mechanisms (e.g. malignancy, inflammatory bowel disease, nephrotic syndrome, diabetes, obesity, etc.). These conditions may induce thrombosis by themselves or contribute to its clinical onset in patients with true thrombophilic states. This is especially the case for patients who are taking contraceptive drugs, are pregnant, have undergone surgery or trauma. The term hypercoagulability states is by no means equivalent to either thrombophilia or CPT. In fact, hypercoagulability may be defined as "activation of blood coagulation" in the presence of specific markers such as fibrinopeptide A and prothrombin fragment F1 + 2. Hypercoagulability is therefore a laboratory rather than a clinical condition and can be a transient feature appearing during certain phases of thrombophilia or CPT. Lastly, conditions involving the presence of hemostatic risk factors for atherothrombosis are simply terms used to describe a statistical-epidemiological relationship between certain hemostatic variables (fibrinogen, factor VII, PAI, etc.) involving the risk of cardiovascular morbidity and mortality but not necessarily indicating a hypercoagulability state.
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PMID:Pro-thrombotic states and their diagnosis. 800 87

Lupus anticoagulants (LA) have been defined as phospholipid-interfering antibodies. Testing for them has become a frequently requested procedure in coagulation laboratories and new methods have recently become available. Activated partial thromboplastin time (aPTT) reagents with reduced levels or different types of phospholipid provide high sensitivity. Correction procedures resistant to heparin and based on aPTT and dilute Russell's viper venom time (DRVVT) tests with added hexagonal phase phospholipids have improved the specificity of testing. Simplified tests based on venom activators of factor X and prothrombin improve the reliability of LA testing and may facilitate the further categorization of circulating anticoagulants. Recent studies on the mechanism of LA derived from various patients have confirmed their heterogeneity, principally in the protein cofactors involved in their interactions with phospholipids. Perhaps one-third of LA require beta 2-glycoprotein 1 to exert an anticoagulant effect. The remainder may require human prothrombin as suggested from studies with reconstituted clotting factor systems.
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PMID:Some recent developments with lupus anticoagulants. 805 62

Anticardiolipin antibodies are produced both in patients with the antiphospholipid syndrome (APS) and in patients with syphilis, but lupus anticoagulant activity has been reported only for the former group. To understand these differences, affinity-purified immunoglobulin G anticardiolipin antibodies from APS (n = 11) and syphilis (n = 5) patients were compared. Only the antibodies from the APS group inhibited prothrombin conversion to thrombin and cross-reacted with phosphatidylserine. These findings may enable better definition of the phospholipid epitopes involved in the hemostatic abnormalities of APS.
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PMID:Differences in functional activity of anticardiolipin antibodies from patients with syphilis and those with antiphospholipid syndrome. 806 29

Snake venoms contain a rich variety of factors affecting the haemostatic mechanism which can be broadly classified as possessing coagulatant, anticoagulant and haemorrhagic activity. Coagulant enzymes include activators of blood coagulation factors II (prothrombin), V and X; anticoagulants include protein C activators, inhibitors of prothrombin complex formation and fibrinogenases which can be further classified according to their specificity for the alpha-, beta- and gamma-chains of fibrinogen. Intermediate between true coagulants and true anticoagulants are the thrombin-like enzymes which bring about clotting in vitro but defibrination (anticoagulation) in vivo. Snake venoms also affect platelets either by inducing or inhibiting platelet aggregation and cause haemorrhage via an action on platelets or via proteolysis of the blood vessel wall. Haemorrhagins also include inter alia, the alpha-fibrinogenases. This rich diversity of snake venom components affecting haemostasis has enabled a range of practical applications to be established including therapeutic anticogulation with thrombin-like enzymes (Ancrod and Defibrase) and laboratory tests for individual haemostatic factors (protein C, prothrombin, factor X and lupus anticoagulant). This broad spectrum of materials in snake venoms suggests some evolutionary advantage to the venom producer, not only for dispatching prey but as agents which 'spread' the venom toxins throughout the body and initiate digestion.
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PMID:Snake venoms affecting the haemostatic mechanism--a consideration of their mechanisms, practical applications and biological significance. 807 11

Lupus anticoagulants (LA) are immunoglobulins (IgG, IgM, IgA or a mixture) which interfere with in vitro phospholipid (PL) dependent tests of coagulation (e.g. APTT, KCT, dilute Russell Viper Venom Time). LA are heterogeneous; consequently, the laboratory diagnosis is difficult and relies on multiple tests. We have developed a sensitive and relatively specific confirmatory test system based on fractions of two snake venoms. Textarin, a protein fraction of Pseudonaja textilis venom (Australian Eastern brown snake), activates prothrombin in the presence of PL, factor V and calcium ions. Ecarin, a protein fraction of Echis carinatus venom, will activate prothrombin in the absence of any cofactors. The activation of prothrombin by Textarin yields thrombin while Ecarin yields meizothrombin. In the presence of LA, the Textarin time is prolonged and the Ecarin time is unaffected. The test results are reported as a ratio of Textarin/Ecarin times (abnormal greater than 1.3). We have evaluated this test system in the following patient populations: LA positive, therapeutically heparinized, stable oral anticoagulated, liver disease, routine preoperative, anticardiolipin antibody positive LA negative, hemophilia A, various other hereditary factor deficiencies or dysfunctional proteins, and specific inhibitors of factor V and factor VIII. The LA positive patients represented a mixed population of autoimmune disease, drug-induced and post-infectious states. Our findings indicate the sensitivity of the Textarin/Ecarin system in the confirmation of LA. In order to use the test system most effectively, it is recommended to incorporate polybrene with Textarin when evaluating heparinized samples. Factor V deficiency and specific inhibitors of factor V yielded, in some instances, false positive results.
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PMID:The Textarin/Ecarin ratio: a confirmatory test for lupus anticoagulants. 816 13


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