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)

Resistance to Activated Protein C (APC) was evaluated using 3 different methods: two of them were based on the prolongation of the Activated Partial Thromboplastin Time (APTT) using 2 different APTT reagents in the presence of APC, whereas the third method was based on the prolongation of prothrombin time when APC is added. The three methods were significantly correlated. APTT-based assays were sensitive to factor XII deficiency, whereas thromboplastin-based assay was sensitive to factor VII deficiency (< 0.5 UI/ml), which surestimates the response to APC. In contrast, an increase in factor VIII (F. VIII) level is associated with a decreased response to APC, when APTT-based assays are used, whereas thromboplastin-based assay is unmodified. During pregnancy, a decreased response to APC is observed, which is not only due to the increase in F. VIII, since thromboplastin-based assay is also modified. In Protein S (PS) immuno-depleted plasma, the low response to APC is corrected by addition of free PS: the thromboplastin-based assay was the most sensitive one to PS deficiency. However, in patients with congenital PS deficiency, there was no correlation between APC-resistance and free PS level. In patients with lupus anticoagulant, discrepancies were observed between the 3 methods, but with a high frequency of low response to APC. For the 3 assays, there was a good differentiation and correlation between normal and pathological results, the thromboplastin-based assay being perhaps the most discriminating. However, 3 unrelated thrombophilic patients showed normal results using thromboplastin-based assay, although they were APC-resistant using APTT-based assays. For 2 patients, this discrepancy can be explained by high levels of F. VIII. For the last patient, an abnormal F. VIII, resistant to APC can be suspected.
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PMID:Resistance to activated protein C: evaluation of three functional assays. 781 60

Lupus anticoagulants (LAs) are immunoglobulins (IgG, IgM, or both) which interfere with in vitro phospholipid (PL) dependent tests of coagulation (e. g. APTT, dilute PT, dilute Russell Viper Venom Time). These antibodies may be identified in a wide variety of clinical settings. With the exception of heparinized patient samples, the presence of LAs is often the most common cause of an unexplained APTT in a routine clinical laboratory. The diagnosis of LAs is difficult due to variable screening reagent sensitivity and intrinsic heterogeneity of LAs. Recently, Rauch and colleagues have shown human monoclonal hybridoma LAs were inhibited by hexagonal (II) phase PLs. In contrast, lamellar phase PLs had no effect. We have evaluated a new assay system, Staclot LA, which utilizes a hexagonal (II) phase PL (egg phosphatidylethanolamine [EPE]) as a confirmatory test for LAs. Plasma samples from the following patient populations were studied: LA positive, heparinized, oral anticoagulated, hemophilia A and B, and specific factor inhibitors (factors V, VIII, IX). Unlike previous studies, the LA positive patients were a mixed population including: autoimmune diseases, drug-induced, and post-infection. Our findings confirm the specificity of hexagonal (II) phase PL neutralization of LAs.
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PMID:A hexagonal (II) phase phospholipid neutralization assay for lupus anticoagulant identification. 812 36

Nine automated, activated partial thromboplastin time (APTT) reagents were evaluated on an automated coagulometer, in comparison with a manual reagent. The study consisted of three separate stages: 1) to choose a reagent that had a working stability between 4 degrees C and 8 degrees C for seven days and heparin sensitivity between 0 and 0.8 iu/ml; ii) assessment of sensitivity to specific factor deficiencies, particularly factors VIII, IX, XI and XII using standardised plasma serially diluted with factor-deficient plasma; and iii) assessment of sensitivity to the presence of a lupus anticoagulant, from a known positive panel. Only one reagent fulfilled all the essential criteria as an acceptable replacement for the manual reagent.
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PMID:Activated partial thromboplastin time reagents: an evaluation. 821 15

We describe the design of a quantitative test for lupus anticoagulants (LA), based on the Activated Partial Thromboplastin Time (APTT) and the Russell Viper Venom Time (RVVT). In this assay system, test plasmas mixed 1:1 with a pooled normal plasma (NP) are tested at a low as well as a high cephalin concentration, using an ACL 3000 automated clot timer. The ratio of these two clotting times, divided by the corresponding ratio for the NP, was defined as the Lupus Ratio (LR) and calculated by means of a computer program. The frequency distribution of the LR in a reference population of 150 healthy individuals was determined, and the 97.5 percentile was defined as the upper reference limit and allocated the value one Lupus Anticoagulant Unit (LA-U). Using dilutions of one strong LA positive plasma, standard curves for LA-U determination were constructed for the APTT as well as the RVVT based test, and fitted with a log-logit computer model. The sensitivity of the tests was comparable to that of the Kaolin Clotting Time (KCT). Plasma samples from warfarin treated patients were uniformly negative, while most heparin-containing plasmas were positive in both tests. Plasmas deficient in Factors V, VIII and IX were negative, whereas one Factor VIII-inhibitor containing plasma was positive in the APTT and negative in the RVVT. The present work shows that it is possible to adapt the APPT as well as the RVVT for LA quantification. With an automated clot timer and computer based calculation of results, the assays are simple and reproducible and have a high sensitivity and specificity.
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PMID:A quantitative, semi-automated and computer-assisted test for lupus anticoagulant. 844 53

C1 inhibitor (C1-inh) was assayed in eight SLE patients presenting with consistently low levels of intact C4. C1-inh antigenic levels were normal in all patients; however, the function of the C1-inh tested against C1s and C1r was variable and outside the normal functional range in seven of the eight patients. The molecular weight of patients' C1-inh protein was 105 kD, corresponding to the size of the intact molecule. The C1-inh gene was analysed in all patients. Restriction fragments generated with TaqI, PstI and HgiAI gave no indication of a major C1-inh gene rearrangement. Direct genomic sequencing of exon VIII revealed three polymorphic point mutations, but there were no changes from the normal gene in or around the reactive-centre residue of C1-inh. Furthermore, we found no evidence for a C1-inh autoantibody in patients which could affect normal C1-inh function in vitro. These results indicate that the etiology of C1-inh dysfunction in SLE is heterogeneous and distinct from that reported in either hereditary or acquired angioedema.
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PMID:C1 inhibitor functional deficiency in systemic lupus erythematosus (SLE). 848 12

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the synthesis of antinuclear antibodies. Nucleosomes-the disc-like-structural unit of chromatin being composed of histones and DNA-are the primary antigenic structure that induces the formation of complement-activating antigen-antibody complexes in basement membranes. The autoreactivity in SLE has been elucidated in drug-induced SLE: Hypomethylation of DNA leads to overexpression of integrin CD 11a/CD 18, increased binding of T-cells to macrophages and B-cells, a higher rate of apoptosis of macrophages and elevated B-cell activity with consecutive production of autoantibodies. Disturbances of apoptosis (e.g. mutation of Fas gene) are relevant also in non drug-induced SLE. The morphologic diagnosis-by light microscopy, immunohistology and electron microscopy-of skin and renal biopsies can confirm the diagnosis and help in prognostic assessment as well as therapeutic decisions in SLE. The value of the morphologic diagnosis in SLE is enhanced by reporting semiquantitative scores of disease activity and chronicity. The antiphospholipid syndrome (APS) is characterized by thrombosis, thrombocytopenia, recurrent fetal loss and antiphospholipid antibodies. APS associated with SLE or other systemic autoimmune diseases has been termed secondary APS. Antibodies in APS are directed against phospholipids and phospholipid-protein complexes. One of these proteins is beta 2-glycoprotein 1. An important mechanism of the increased rate of thrombosis in APS is probably the inhibition of the protein C catalyzed inactivation of clotting factors V and VIII. Venous thrombosis with recurrent pulmonary emboli and arterial thrombi in brain, heart and kidney (thrombotic microangiopathy) can lead to divergent clinical manifestations in APS.
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PMID:[Systemic lupus erythematosus and antiphospholipid syndrome]. 906 4

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by the synthesis of antinuclear antibodies. Nucleosomes- the disc-like structural units of chromatin, composed of histones and DNA-are the primary antigenic structure that induces the formation of complement-activating antigen-antibody complexes in basement membranes. The autoreactivity in SLE has been elucidated in drug-induced SLE: hypomethylation of DNA leads to overexpression of integrin CD11a/ CD18, increased binding of T-cells to macrophages and B-cells, a higher rate of apoptosis of macrophages, and elevated B-cell activity with consecutive production of autoantibodies. Disturbances of apoptosis (e.g. mutation of Fas gene) are relevant also in non-drug-induced SLE. The morphologic diagnosis-by light microscopy, immunohistology and electron microscopy-of skin and renal biopsies can confirm the diagnosis and help in prognostic assessment as well as therapeutic decisions in SLE. The value of the morphologic diagnosis in SLE is enhanced by reporting semiquantitative scores of disease activity and chronicity. The antiphospholipid syndrome (APS) is characterized by thrombosis, thrombocytopenia, recurrent fetal loss and antiphospholipid antibodies. APS associated with SLE or other systemic autoimmune diseases has been termed secondary APS. Antibodies in APS are directed against phospholipids and phospholipid-protein complexes. One of these proteins is beta 2-glycoprotein 1. An important mechanism of the increased rate of thrombosis in APS is probably the inhibition of the protein C-catalyzed inactivation of clotting factors V and VIII. Venous thrombosis with recurrent pulmonary emboli and arterial thrombi in brain, heart and kidney (thrombotic microangiopathy) can lead to divergent clinical manifestations in APS.
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PMID:[Systemic lupus erythematosus and antiphospholipid syndrome]. 908 61

We investigated whether Hepcheck heparin removal filters could remove residual platelets from platelet-poor plasma (PPP) without compromising samples for lupus anticoagulant (LA) testing. Furthermore we assessed what effect, if any, plasma filtration has on various clotting tests that form the foundation for LA testing. Citrated blood was obtained from 35 normal donors. Two sets of citrated tubes were processed in order to obtain PPP. Citrated blood was also obtained from a single donor to check the actual amounts of platelets removed by the Hepcheck filtration device. One set of PPP samples was filtered using the Hepchek filter device and the other was not processed, i.e. unfiltered. Prothrombin time (PT), activated partial thromboplastin time (APTT), and kaolin clotting time (KCT) were performed on both unfiltered and filtered samples that were tested immediately and after freezing at -70 degrees C for 24 h. Platelet counts on the single donor's citrated plasma were dramatically reduced after filtration. PT and APTT values showed small but statistically significant differences between unfiltered and filtered plasmas whether these were fresh or frozen samples. However, these differences were not clinically significant. KCT data showed statistical and clinical differences between unfiltered and filtered plasmas whether fresh or frozen plasmas were used. In contrast, KCT values were similar if unfiltered, fresh plasmas or filtered, frozen plasmas were used. Coagulation factor assays for factors VIII, IX and X were performed on both sets of PPP samples after freezing to determine if the filtration device affected these levels and would as a result, compromise APTT based lupus testing. Factor IX levels demonstrated a loss of activity following use of the device but no change was observed in factor VIII or factor X. Von Willebrand factor antigen and function as well as multimer structure were not affected by the filtration device in 10 normal donors. Filtering plasmas of two donors with a history of an LA dramatically prolonged clotting times for APTT, Dilute Viper Venom Time, mixing studies, and STACLOT LA tests in comparison with unfiltered plasmas. The data indicate that plasma filtration using the Hepchek device does not adversely affect coagulation testing. Furthermore samples requiring testing for the lupus anticoagulant can be filtered and subsequently frozen and compare favorably with freshly processed samples.
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PMID:Rapid removal of platelets from plasma utilizing the Hepcheck heparin removal filter. 910 33

We have evaluated the technical performance of the MDA-180 automated coagulation analyser in a working diagnostic hemostasis laboratory environment. The analyser has been on site now for over 18 months, and has undergone considerable testing. More than 22,000 samples have been processed, with over 90% of these via the MDA-180's cap-piercing facility. The instrument has been primarily assessed for its technical ease of use and continued reliability, as well as its analytical performance. The instrument has also been successfully interfaced to, and used with, our Laboratory information (CERNER PATHNET) system. A major feature of our evaluation has been an assessment of the MDA-180's ability to perform assays currently performed using alternative methodology or instrumentation (eg; ELISA methodology or the Coagamate-X2 and ACL-300R instruments), as well as its potential to streamline the technical performance of some of these assays. We have co-evaluated the following assays: PT/INR, APTT, TT, Fibrinogen, Protein C, ATIII, Factors II, V, VII, VIII, IX, X, XI, and XII, Lupus anticoagulant (dRVVT), and heparin (alpha Xa). In addition, a number of different reagents (particularly for PT and APTT assays) have been tested on the instrument. Intra-assay and inter-assay variation appears to be remarkably low (five different plasmas tested: PT: 0.6 to 1.3% and 0.5 to 1.3% respectively; APTT: 0.7 to 3.2% and 0.6 to 3.6% respectively; single day analysis). Other comparative assessment data typically showed good correlation to existing test assay systems. A review of other features which may enhance or detract from the instrument's worth in a given hemostasis laboratory is also presented. In summary however, we conclude that the instrument is reliable, easy to use and capable of fast sample through-put.
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PMID:The MDA-180 coagulation analyser: a laboratory evaluation. 921 38

In the present study CoaguCheck Plus (CCP), a coagulation test system using whole blood, was evaluated with respect to its comparability with widely distributed conventional routine coagulation assays. A correlation of r = 0.997 (p < 0.0001) was found between INR of CCP-prothrombin time (CCP-PT) and Thrombotest (KC-1 analyzer) in patients on oral anticoagulant therapy. A correlation of r = 0.899 (p < 0.001) between CCP-aPTT and Actin ES aPTT (STA analyzer) was found in heparinized patients. Impaired hepatic hepatic coagulation factor synthesis in liver cirrhosis patients was detected by CCP-PT with a sensitivity of 0.75 and by Normotest (STA analyzer) with a sensitivity of 0.92. Those patients with normal CCP-PT values and liver disease had, only mild reductions (> 30% of normals) in coagulation factors II, V, VII or X. CCP-aPTT was also performed in patients with a deficiency in the so called endogenous coagulation factors VIII, IX, XI and XII. CCP-aPTT showed a sensitivity similar to that of Actin FS aPTT in the detection even of mild deficiencies in factors VIII, IX and XII; factor XI deficiency was however detected only in patients with severe (< 12% of normals) disease; lupus anticoagulants were detected with a high sensitivity.
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PMID:Evaluation of bedside prothrombin time and activated partial thromboplastin time measurement by coagulation analyzer CoaguCheck Plus in various clinical settings. 930 17


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