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)

We compared the sensitivity and specificity of a tissue factor-based assay (FVR) with the addition of a phospholipid/silica preparation, to the commercially available aPTT-based method, APCR (CoatestTM), and a modified aPTT-based method (APCM) which utilized factor V-depleted plasma, for the detection of the factor V Leiden mutation. A total of 110 patients were included in this study. This included 32 patients on coumadin therapy, 7 patients on heparin therapy, 5 patients on both anticoagulants therapy, and 24 patients who were positive for anticardiolipin antibody (ACL) and/or lupus inhibitor (LI). Our data demonstrate that the FVR is not affected by anticoagulation treatment or ACL/LI antibodies, whereas in the APCR method, 33 patients cannot be determined either due to the anticoagulant therapy or presence of the ACL and/or LI. With the APCM method, the clotting endpoint could not be determined in 1 patient due to the presence of a strong LI. The additional phospholipid/silica material utilized in the FVR enhanced the APC degradation of factor Va and therefore sharpened the demarcation between the factor V Leiden-positive and -negative patients. The sensitivity for the APCR, APCM and FVR was 42, 97 and 100% respectively. The specificity for the APCR, APCM and FVR was 94, 96 and 100% respectively.
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PMID:A highly specific functional test for factor V leiden: A modified tissue factor assay for activated protein C resistance. 973 Nov 10

Genetic defects of antithrombin (AT) or one of the components of the protein C pathway are associated with hereditary thrombophilia. Laboratory assays are currently available to diagnose and type hereditary thrombophilia due to deficiency or dysfunction of one of the anticoagulant factors antithrombin (AT), protein C (PC) and protein S (PS), and APC resistance without the need of DNA analysis. There are no functional tests for the prothrombin mutant G20210A and thrombomodulin mutations, which can be diagnosed by a PCR-based test or by gene analysis, respectively. Hereditary AT deficiency is classified in a quantitative type I and three functional type II deficiencies affecting the reactive site (RS), heparin binding site (HBS), or pleiomorphic site of the AT protein. All four types of hereditary AT deficiencies can be diagnosed by a heparin cofactor assay and one immune assay in combination with crossed immunoelectrophoresis of the AT protein. The combination of an enzyme-linked immunoadsorbent assay (ELISA) and a functional Protac-APTT-based assay for PC will detect quantitative type I and dysfunctional type II PC deficiencies. There is a significant overlap in PC antigen and functional levels between heterozygotes of PC deficiency and normals leaving a gray zone of uncertainty in differentiating congenital PC deficiency and normal individuals. Accurate diagnosis of hereditary PS deficiency should be a combination of tests aimed to measure free PS activity and antigen and total PS antigen levels. APTT-, Xa-, and RVVT-based APC-resistance tests, when test plasmas are diluted in factor V deficient plasma, have increased in sensitivity and specificity to 100% for the discrimination of normal individuals from heterozygotes and homozygotes for factor V Leiden. The RVVT-based APC-resistance test provides better separation of factor V Leiden and normals in the various clinical settings, lupus anticoagulant in particular. The modified APC-resistance tests also claim a separation between heterozygotes and homozygotes for factor V Leiden in the normal population, asymptomatic subjects, and thrombosis patients. Below a certain cut-off level, a minor overlap of normalized APC ratios between heterozygotes and homozygotes for factor V Leiden of thrombosis patients has been shown in one study, which still points to the need to perform the more time consuming and expensive DNA test to identify heterozygotes from the more clinically significant homozygotes. The prothrombin-based APC-resistance test, which measures thrombin activated factor Va in highly diluted test plasma, appears to be the most sensitive and specific of all APC-resistance tests and separates normal individuals from heterozygotes and heterozygotes from homozygotes for factor V Leiden without the need of confirmation by a DNA test.
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PMID:Laboratory diagnosis of hereditary thrombophilia. 976 48

A new automated method for screening defects in the Protein C Pathway (PCP) was evaluated. The "PCP test" is based on a phospholipid-rich Russells viper venom reagent, insensitive to heparin and lupus anticoagulants. To minimize interference from other clotting variables, ratios of the clotting time with and without the addition of a protein C activator were usually determined. Plasma samples from healthy volunteers, patients untreated or on oral anticoagulants, patients with factor V Leiden with and without treatment, and patients with protein C and/or S deficiencies were tested. Mixing patient plasmas 1:1 with individual plasmas deficient in factor V, protein C or S was evaluated for identifying the nature of defects by shortening the screening test. The PCP test was found to be sensitive to APC resistance due to factor V Leiden and by mixing with factor V deficient plasma was also useful despite the effects of oral anticoagulants. Results in the group of patients with previous low protein C or S levels suggest that the method has a better sensitivity to protein C than to protein S deficiency. The automated test was simple to use and gave a between-run coefficient of variation below 3% on normal plasmas.
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PMID:A protein C pathway (PCP) screening test for the detection of APC resistance and protein C or S deficiencies. 976 52

We explored the association of inflammatory mediators and markers of autoimmune and coagulation disorders with cerebral palsy (CP), examining 53 analytes in dried neonatal blood of 31 children with spastic CP, most born at term, and 65 control children. Ultramicroanalysis was performed by recycling immunoaffinity chromatography coupled with laser-enhanced fluorescence and chemiluminescence detection. Reactive antibodies to lupus anticoagulant, anticardiolipin, antithrombin III, and the translational product of the factor V Leiden mutation were isolated by recycling immunoaffinity chromatography and measured by capillary electrophoresis with chemiluminescence-enhanced immunoassay. Higher concentrations of interleukins (ILs) 1, 8, 9, tumor necrosis factor-alpha, and RANTES were observed in these children with CP than in any control child. There were also substantial elevations of IL-6, 11, 13, and other chemokines and colony-stimulating factors in children with CP. Antiphospholipid antibody was present in a titer of 1:100 or greater in 4 children with CP and no control child. Using cuts empirically chosen by recursive partitioning, we found higher concentrations of antibody to antithrombin III, to a translational product of factor V Leiden mutation, and to proteins C and S in children with CP than in controls. We conclude that inflammation and these coagulation abnormalities, which have interacting pathways, are important in the etiology of CP.
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PMID:Neonatal cytokines and coagulation factors in children with cerebral palsy. 977 66

Activated protein C (APC) resistance has been identified in many studies as a major cause of venous thromboembolism. The most common genetic polymorphism of clinical relevance causing APC resistance is the factor V Leiden mutation (FVL). Besides the FVL mutation, several acquired risk factors like lupus anticoagulant or elevated levels of acute phase proteins are known to induce APC resistance in plasma. Oral contraceptive (OC) users are known to be at higher risk for deep vein thrombosis than nonusers. Therefore, this BATER-cohort study (Bavarian Thromboembolic Risk Study) was conducted in Bavaria, Germany, during 1996-97. A total of 821 women were randomly selected and enrolled in the study to examine the effects of OCs on hemostasis variables known to be risk factors for venous thromboembolism, especially looking for acquired APC resistance and the plasmatic factors of the protein C system. Findings revealed that APC resistance was significantly lower in OC users in comparison with nonusers and was not attributable to the increased factor VIII:C levels. APC methods applied in this study revealed no significant difference between OC users of any type. Therefore, an increase of the risk related to OC use and/or FVL mutation was statistically insignificant.
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PMID:Resistance to activated protein C in women using oral contraceptives. 983 8

Activated protein C (APC) is a naturally occurring anticoagulant that interacts with factor V and VIII to inhibit the clotting cascade. The prevalence of APC resistance among Korean patients with deep vein thrombosis is ill defined. The aim of the present study was to investigate the prevalence of APC resistance and factor V Leiden mutation in Korean patients with deep vein thrombosis. The presence of factor V Leiden mutation was determined in 49 patients who visited Asan Medical Center. APC ratio was performed in 33 individuals from the above 49 patients. Three patients were excluded from the analysis because their baseline aPTT was prolonged. Resistance to APC was diagnosed when the APC ratio was below 2.55. APC resistance was documented in 8 individuals, representing 27% (8/30) of the patients on whom APC resistance test was performed. The 2 patients, who showed APC resistance, were positive for lupus anticoagulant. None of the 49 patients demonstrated factor V Leiden mutation. These findings indicate that factor V Leiden mutation is rare and APC resistance is less prevalent in Korean patients with deep vein thrombosis than in Caucasians. APC resistance not caused by factor V Leiden mutation may be a risk factor for deep vein thrombosis in this population.
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PMID:Low prevalence of activated protein C resistance and coagulation factor V Arg506 to Gln mutation among Korean patients with deep vein thrombosis. 988 65

Fifteen patients with cerebral venous thrombosis were ascertained retrospectively. Their case notes were reviewed, and stored or new blood was assayed for factor V Leiden (FVL) mutation, prothrombin gene mutation 20201A, and 5,10 methylene tetrahydrofolate reductase (MTHFR) C677T mutation. A clinical risk factor was identified in 13 patients--the oral contraceptive pill (5), puerperium (1), HRT (1), mastoiditis (1), dehydration (1), lumbar puncture and myelography (1), carcinoma (1), lupus anticoagulant (2). In addition, two patients had the FVL mutation and five (one of whom also had the FVL mutation) were homozygous for the MTHFR mutation. The latter showed a higher than expected frequency compared to 300 healthy controls from South Wales (OR 3.15.95% Cl 1.01-9.83). No patient had the prothrombin 20201A mutation. Two patients died and three had a monocular visual deficit following anticoagulation (13) or thrombolytic (2) treatment, but there was no association between the presence of a primary prothrombotic risk factor and outcome. These results confirm the importance of investigating patients for both clinical predisposing factors and primary prothrombotic states.
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PMID:Inherited prothrombotic risk factors and cerebral venous thrombosis. 1002 25

The aim of this study was to evaluate critically the recently modified activated-partial-thromboplastin-time (APTT)-based activated protein C (APC)-resistance tests, which are more specific for the factor V Leiden mutation than the first generation APC-resistance tests. The only modification to these tests is the predilution of the plasma sample in factor-V-deficient plasma. The intended effect of this predilution is to bring the concentrations of all clotting factors, except factor V, to the same normal levels. This, in principle, makes the tests also suitable for assaying the plasma of patients treated with oral anticoagulants and heparin, or of patients with a lupus anticoagulant. However, not every factor-V-deficient plasma is suitable for this application. Because the factor V:factor VIII ratio is important in establishing the APC ratio, the factor-V-deficient plasma should contain a sufficiently high factor VIII concentration. We also found that the optimal dilution to obtain the same APC ratios for patients, whether or not treated with coumarins or heparin, is not the same for each test or factor-V-deficient plasma. We compared two modified APTT-based APC-resistance tests (one developed in our laboratory and one commercial) with respect to their ability to discriminate between carriers and non-carriers of the factor V Leiden mutation. Both modified tests gave complete separation of carriers and non-carriers of the factor V Leiden mutation whether or not they are treated with anticoagulants. This makes these tests very suitable for routine screening.
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PMID:Careful selection of sample dilution and factor-V-deficient plasma makes the modified activated protein C resistance test highly specific for the factor V Leiden mutation. 1007 Aug 30

Budd-Chiari syndrome is characterized by hepatic venous outflow obstruction. Although myeloproliferative disorders are usually responsible for this severe thrombotic disorder, deficiency or dysfunction of the natural anticoagulants can be involved. Resistance to activated protein C caused by factor V Leiden mutation has been recently identified as a major cause of thrombophilia. We report 6 patients with Budd-Chiari syndrome associated with factor V Leiden mutation combined with another acquired thrombophilic state (myeloproliferative disorder and lupus anticoagulant in 3 cases) and without another thrombophilic disorder in the other 3 cases. We conclude that factor V Leiden mutation should be evaluated in any case of hepatic vein occlusion because the prevalence of this mutation in the general population is high.
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PMID:Budd-Chiari syndrome associated with factor V leiden mutation: a report of 6 patients. 1007 47

Thrombophilia is defined as an increased tendency to thrombosis and can be inherited or acquired. The thrombotic events in patients with inherited thrombophilia tend to occur at a young age, are often idiopathic, recurrent and may occur at unusual sites (e.g. mesenteric, portal and cerebral veins and in inferior vena cava). The most common of the hereditary defects appear to be antithrombin, protein C, protein S deficiency, which account for 10% of individuals presenting with venous thromboembolism, resistance to anticoagulant effect of activated protein C (APC-R), which is present in 17 to 64% of patients with thrombosis and prothrombin 20210 G-->A variant with 6% prevalence in patients with thrombosis. APC-R is due in 90% to the presence of factor V Leiden. Rarer defects include heparin cofactor II (HC II), plasminogen or tissue plasminogen activator deficiency (TPA), elevated plasminogen activator inhibitor-1 (PAI-1) and dysfibrinogenemia. The most common acquired defects are antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies). Hyperhemocystinemia is responsible as well for arterial as venous thrombosis. A substantial proportion of venous thrombotic events occurs spontaneously, i.e. without a precipitating event. Risk factors for thrombosis include surgery, trauma, immobility, congestive heart failure, pregnancy including puerperium and oral contraceptive usage. The thrombotic risk is increased in patients who are homozygous for factor V Leiden and markedly increased in patients with combined defects.
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PMID:[Thrombophilic states]. 1035 55


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