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)

Plasma proteins which interfere with blood coagulation have often been described in patients with systemic lupus erythematosus (SLE). The most frequent type interferes with the conversion of prothrombin to thrombin and thus prolongs the prothrombin time. Infrequently, SLE patients exhibit anticoagulants which appear to block the earlier stages of coagulation such as those involving factor VIII or the formation of activated factor XI (factor XIa). The anticoagulant reported here was studied by means of a sequential clotting system utilizing crude coagulation factors and was noted to interfere with the action of activated plasma thromboplastin antecedent (PTA) during the activation of factor IX. This anticoagulant was found in gamma-globulin-rich ethanol fractions of plasma. After gel filtration, it was found principally in fractions containing IgM globulins but also, to a lesser extent, in IgG-rich fractions. In this respect, it is similar to anticoagulants reported in certain other cases of SLE. Attempts to confirm the immunoglobulin nature of the anticoagulant by immunoabsorption were, however, inconclusive
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PMID:Studies on a circulating anticoagulant in systemic lupus erythematosus: evidence for inhibition of the function of activated plasma thromboplastin antecedent (factor XIa). 23 89

In a patient with systemic lupus erythematosus, anticoagulant activity directed against factor XI was found together with thrombocytopenia. In the serum globulin fraction, antiplatelet antibodies and an activity-inhibiting platelet aggregation could also be found. A possible correlation between the inhibition of platelet aggregation and the anticoagulant activity directed against factor XI is discussed.
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PMID:Circulating anticoagulant against factor XI and thrombocytopenia with platelet aggregation inhibition in systemic lupus erythematosus. 41 Feb 26

A lupus-type anticoagulant which causes strong inhibition of the partial thromboplastin time with kaolin (PTTK), the stypven time, and the thrombin generation tests has been investigated. All tests for platelet function were normal, as were all specific coagulation factor assays with the exception of a slightly reduced factor XI in this patient. A diethylaminoethyl-cellulose-immunoglobulin (DEAE-cellulose-IgG) fractionation of the patient's plasma produced two peaks containing inhibitory activity in the PTTK test. The first of these peaks had a cloudy appearance, suggesting the presence of immunoglobulin aggregates. Studies with IgG aggregates prepared from normal IgG and from the patient's IgG demonstrated that such aggregates were not the cause of inhibition. It was possible to neutralize the inhibitory activity of the purified IgG but not platelet-poor plasma (PPP) with a rabbit anti-IgG. The inhibition of the patient's PPP in the thrombin generation, the contact product, and the stypven time tests were corrected by the inclusion in the test system of platelets activated either by aggregation due to adenosine diphosphate (ADP) or formalin fixation and washing. These studies lend support to earlier findings that platelets interact at several sites in the coagulation cascade.
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PMID:Demonstration of a platelet bypass mechanism in the clotting system using an acquired anticoagulant. 73 36

An elderly man with procainamide hydrochloride-induced lupus syndrome had a circulating anticoagulant against factor XI and a biologic false-positive (BFP) test result for syphilis. This was not associated with hemorrhagic problems. The activity of the circulating anticoagulant and the BFP disappeared within days following discontinuation of procainamide and the administration of corticosteroids.
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PMID:Circulating anticoagulant in the procainamide-induced lupus syndrome. 92 27

A 70 year old male patient admitted for coronary bypass surgery presented with a procainamide-induced lupus syndrome. This syndrome included a LLAC with a positive IgM ACA titer as well as a factor XII inhibitor. These drug-induced inhibitors were superimposed upon the patient's congenital deficiency of factor XI. The methods used to identify these abnormalities are described together with the replacement therapy employed to cover the surgical procedure. The long-term withdrawal of procainamide was associated with correction of all coagulation abnormalities except the factor XI deficiency.
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PMID:Procainamide-induced circulating anticoagulants in a congenitally-deficient factor XI patient. 247 3

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

Traditionally, factor XI has been determined in the clinical laboratory by a modified activated partial thromboplastin time assay (aPTT) with factor XI-deficient plasma as the substrate. Coagulant assays, however, have high coefficients of variation. We previously developed a chromogenic assay for factor XI that required equipment not normally found in a clinical laboratory. We now present a modification of that assay, which is performed in 96-well microplates and can be done in any clinical laboratory or physician's office. Plasma is subjected to a brief acidification to inactivate most of the plasma protease inhibitors. Soybean trypsin inhibitor is included to stabilize the factor XIa that is generated. Kaolin is used as the contact activating surface, and the chromogenic substrate, S-2366, is used to measure the factor XIa that is formed. Results of the assay, performed in three groups of subjects, correlate well with results of the coagulant assay as performed in our laboratory and clearly differentiate between total factor XI deficiency and the deficiency of any of the other contact proteins. Unlike coagulation assays, the chromogenic assay is not influenced by the presence of heparin. Furthermore, it is not affected by lupus anticoagulants, which are antibodies directed against acidic phospholipids. Two plasma samples from patients with acquired factor XI inhibitors showed dissociation between coagulant and amidolytic activity, suggesting that the antibodies were not primarily directed toward the active site of factor XIa, which is responsible for its amidolytic activity. In contrast, patients with severe congenital deficiency of factor XI showed no activity by either assay.
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PMID:A simple and accurate microplate assay for the determination of factor XI in plasma. 337 14

A 42-yr-old woman with systemic lupus erythematosus without bleeding diathesis developed a prolonged activated partial thromboplastin time that was not corrected by normal plasma. An inhibitor that acted rapidly and inactivated 0.5 U/ml plasma thromboplastin antecedent (PTA, factor XI) at a 1:200 plasma dilution was demonstrated. In addition to a low titer of PTA (less than 0.01 U/ml), plasma assayed at 20-fold dilution also showed low titers of Hageman (factor XII, 0.02 U/ml), Fletcher (plasma prekallikrein, 0.02 U/ml), and Fitzgerald (high molecular weight kininogen, less than 0.01 U/ml) factors. The titer of these factors, except PTA, returned to normal upon further plasma dilution or upon removal of the inhibitor by protein A adsorption. Thus, the inhibitor appeared to interfere with these clotting factor assays, possibly by inactivating PTA in the substrate plasmas in the test system. Its specificity was further confirmed. The inhibitor did not interfere with surface-induced proteolytic cleavage of Hageman factor. Surface-induced generation of plasma kallikrein activity (amidolysis of H-D-pro-phe-arg-pNa and cold-promoted factor VII activity enhancement) requires only Hageman, Fletcher, and Fitzgerald factors and was normal. Reactions requiring all 4 contact phase factors, including PTA, such as surface-induced generation of plasmin activity (amidolysis of H-D-val-leu-lys-pNa) and activated Christmas factor (factor IXa) activity, were defective. Furthermore, the inhibitor bound to agarose-protein A inactivated and removed PTA selectively from normal plasma. The inhibitor was an IgG-lambda autoantibody that precipitated PTA. The inactivated activated PTA (factor XIa) without the requirement for an additional cofactor. Furthermore, it inhibited surface-induced activation of PTA by interfering with its proteolytic cleavage upon glass surface exposure and with its binding onto the reactive surfaces.
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PMID:A unique precipitating autoantibody against plasma thromboplastin antecedent associated with multiple apparent plasma clotting factor deficiencies in a patient with systemic lupus erythematosus. 642 50

A 56 year old white man with psoriasis without serologic evidence of systemic lupus erythematosus was found to have a circulating anticoagulant against Factor XI with a low activity of Factor IX which could not be fully explained. The activity of the circulating anticoagulant was not potentiated on incubation after addition of normal plasma and it was still persisting after 15 months despite periodic treatment with methotrexate and topical steroid creams. This acquired anticoagulant neither protected the patient from myocardial infarction nor produced any bleeding complications.
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PMID:Circulating anticoagulant against factor XI in psoriasis. 695 28

A variety of coagulation abnormalities has been described in systemic lupus erythematosus (SLE). We report a unique SLE patient with an acquired factor XI deficiency. The low factor XI levels were not due to a classical coagulation inhibitor, but to a plasma factor (probably an immunoglobulin) that selectively bound factor XI. The factor XI deficiency improved after treatment with corticosteroids. Thus it is possible that in SLE immune complexes may bind clotting factors making them unavailable for use in the coagulation cascade.
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PMID:Acquired factor XI deficiency in systemic lupus erythematosus. 716 14


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