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)

We studied both inherited and acquired activated protein C (APC) resistance in a group of 22 patients with primary antiphospholipid syndrome (APS). The APC resistance genotype was assessed using a PCR-based analysis for the factor V R506Q (Leiden) mutation. One patient with primary APS was found to be heterozygous for the factor V Leiden mutation. He and other family members were affected by severe thrombophilia and had a familial form of primary APS. The APC resistance phenotype was assessed by measuring the prolongation of the activated partial thromboplastin clotting time in response to APC. It was found in five out of six patients with APS, in one of them transiently. We have found that the APC resistance phenotype is more frequent than the genotype in primary APS. It would seem that patients with thrombophilia should be investigated for APC resistance even if found to have antiphospholipid antibodies and/or lupus anticoagulants.
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PMID:Activated protein C resistance phenotype and genotype in patients with primary antiphospholipid syndrome. 873 42

Thromboembolic complications are frequently observed in patients with systemic lupus erythematosus (SLE). Significant associations have been reported between these complications and the presence of antiphospholipid antibodies, notably the lupus anticoagulant and anticardiolipin antibodies. Factor V Leiden is a genetic disorder associated with an increased risk of venous thrombosis. We studied these factors in 173 patients with SLE in relation to both arterial and venous thrombosis. The frequency of factor V Leiden in SLE patients in comparable to that in the Dutch population (5%) and a risk factor for venous thrombosis (odds ratio 4.9; CI 1.2-19.6), but not for arterial thrombosis. The lupus anticoagulant is a risk factor for both arterial thrombosis (odds ratio 7.1: CI 2.9-17.4) and venous thrombosis (odds ratio 6.4; CI 2.7-15.4). From multivariate analysis, both the lupus anticoagulant and factor V Leiden appeared independent risk factors for venous thrombosis.
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PMID:Factor V Leiden, antiphospholipid antibodies and thrombosis in systemic lupus erythematosus. 890 88

Resistance to the anticoagulant effects of activated protein C (APC) is now considered the most prevalent cause of inherited thrombophilia. The great majority of patients with activated protein C resistance (APCR) have a missense mutation in the factor V molecule (factor V Leiden, FVR506Q) resulting in defective inactivation of factor Va due to a loss of an APC cleavage site. The diagnosis of APCR has been based upon the inability of APC to prolong the activated partial thromboplastin (aPTT) clotting time in subjects with APCR. However, this assay has a number of deficiencies which limit its general use. We have evaluated a newly described one-stage tissue factor dependent factor V coagulation assay for APCR in 117 patients and controls and compared the results of this assay in a blinded manner to a polymerase chain reaction (PCR) based assay for the molecular defect of factor V Leiden. 43% (50/117) of the patients studied were receiving coumadin or heparin, or had a lupus anticoagulant. The tissue factor dependent factor V assay had 100% specificity and sensitivity for factor V Leiden and successfully predicted a homozygous state in the three documented homozygotes. The PCR-based assay for factor V Leiden resulted in a single false positive assay due to a silent A to C transition at nucleotide 1692 resulting in the loss of the Mnl restriction endonuclease cleavage site. The single-stage tissue factor dependent factor V assay is a highly sensitive and generally applicable assay for APCR.
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PMID:Evaluation of a tissue factor dependent factor V assay to detect factor V Leiden: demonstration of high sensitivity and specificity for a generally applicable assay for activated protein C resistance. 894

Activated protein C resistance (APCR) has proved to be a frequent finding in association with thrombosis. The majority of patients with APCR have been found to be homozygous or heterozygous for the polymorphic variant factor V Q506 (factor V Leiden; FVQ506). However a small number of patients have APCR as assessed by functional tests but do not possess the FVQ506 polymorphism. Some of these cases are due to the presence of a lupus type anticoagulant but in this report we demonstrate that the remainder are almost entirely (nine out of ten) associated with an elevated level of FVIIIc. Spiking experiments in normal patient plasma and venous occlusion tests demonstrated that elevation of the FVIIIc results in a reduced APCR ratio and shortening of the APTT. Variation in FVIIIc, in conjunction with other factors, may therefore explain the variable phenotype associated with FVQ506 and the phenomenon of thrombosis associated APCR in the absence of FVQ506. We conclude that FVIIIc as well as FVQ506 should be taken into account when assessing thrombotic risk. APCR, elevated FVIIIc and shortened APTT have all been previously identified with an increased risk of thrombosis. It follows that resistance to APC may arise from a number of factors and is in itself a risk factor for thrombosis. The net effect of these factors is assessed in the functional test for APCR and it may be premature therefore to replace functional tests for APCR with DNA analysis alone.
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PMID:The influence of factor VIII on measurement of activated protein C resistance. 903 55

Primary hypercoagulable states are hereditary disorders that result in arterial and venous thromboses. The purpose of this report is to present three patients with hypercoagulable states, and offer current guidelines for diagnosis and treatment. Primary hypercoagulable disorders such as antithrombin III, protein C and protein S deficiencies, fibrinolytic disorders such as decreased plasminogen levels and plasminogen activator deficiency, and antiphospholipid syndromes such as anticariolipin antibody and lupus anticoagulants will be reviewed. We will emphasize clinical characteristics that should prompt evaluation for hypercoagulation, appropriate laboratory tests for hypercoagulable disorders, and treatment. Other secondary and recently investigated hypercoagulable disorders, including heparin-associated thrombocytopenia, homocystinemia, lipoprotein (a), plasminogen activator inhibitor, and factor V Leiden, will also be reviewed.
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PMID:The surgical implications of primary hypercoagulable states. 904 71

The activated protein C resistance (APC-R) ratios in 50 patients with steady state homozygous sickle cell (SS) disease and 59 healthy AA controls was measured. There was a significant reduction in median APC-R ratio in sickle cell disease compared to controls. This reduction in APC-R ratio was not explained by (1) the presence of the factor V Leiden, found in only one of 165 patients with SS disease including those tested for APC-R, or (2) the presence of lupus anticoagulants. However, the raised levels of factor VIIIC in SS patients in this study may be contributing to increased resistance to APC, which in turn may contribute to the vaso-occlusive complications of SS disease.
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PMID:Activated protein C resistance in homozygous sickle cell disease. 907 31

The most common commercially available test measuring activated protein C (APC) resistance relies on the the anticoagulant response to added APC in an activated partial thromboplastin time (APTT) based method. Another method is a Russell Viper venom time (RVVT) based system. To improve the specificity for factor V Leiden of the APTT based method, pre-dilution of test plasma in FV-deficient plasma has recently been recommended. In this study we tested the relative suitabilities of the APTT-based system, the RVVT-based system and their corresponding assays modified by pre-dilution in FV-deficient plasma, for screening asymptomatic subjects, a group of thrombophilic patients (in particular those with low APC ratios), patients on oral anticoagulants, and patients with lupus anticoagulant (LAC). We found the RVVT-based assay to be superior to the APTT-based method in the separation of normals from those with FV Leiden mutation both in asymptomatic subjects and in the thrombophilic patient group. Both modified assays demonstrated a sensitivity and specificity of 100% for FV Leiden, as verified by genotyping in asymptomatic subjects, thrombophilic patients and patients on oral anticoagulants, with the modified RVVT-based assay giving better separation between normals and FV Leiden. Inhibition of phospholipid-dependent coagulation by LAC antibodies rendered the APTT-based system less suitable than the phospholipid-rich RVVT-based one, and as nine of the 20 LAC-positive patients were on warfarin, we showed only the modified RVVT assay to be a reliable predictor of factor V Leiden in this patient group.
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PMID:A comparison between two activated protein C resistance methods as routine diagnostic tests for factor V Leiden mutation. 921 78

The effect of antiphospholipid antibodies (aPL) on the action of activated protein C (APC) was examined in 32 patients: 19 with lupus anticoagulant (LA), 6 with anticardiolipin antibodies (aCL), and 7 with LA and aCL. Eighteen patients had a ratio of activated partial thromboplastin time (APTT) with APC to APTT without APC (APTT ratio) <2.06 (cut-off level) and no factor V Leiden mutation; these patients showed APC-resistance (APC-R) phenotype. The mean prolongation of APTT after addition of APC in a control group was 45.3 seconds, with a lower limit of 31.4 seconds. Only 3 of the 18 patients with low APTT ratio had a prolongation of <31.4 seconds; they were classified as true APC-R phenotype, whereas the other 15 patients were classified as spurious APC-R. Of the 3 patients with true APC-R, 2 had deep venous thrombosis, 1 with pulmonary embolism, and the third had recurrent abortion. Of the other 15 patients, 2 had had ischemic stroke, 1 had recurrent abortion, and 12 were asymptomatic. Circulating APC level was measured in 14 of the 18 aPL patients with a low APTT ratio; it was lower than the normal lower limit in 4 patients and within the lower limit in 2. Three of the 4 patients with reduced APC levels had a history of thrombosis. We conclude that patients with aPL who show APC-R phenotype due to a low APTT ratio without the factor V Leiden mutation can be classified into two groups: true and spurious APC-R phenotype. Since those with true APC-R phenotype could have greater thrombotic risk, adequate classification of these patients is important. Moreover, aPL can sometimes interfere with the activation of protein C, thus reducing the circulating levels of APC, and this could constitute another thrombotic risk factor.
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PMID:Activated protein C resistance phenotype in patients with antiphospholipid antibodies. 928 Jan 48

We compared the performance characteristics of a commercial dilute Russell's viper venom (DRVV)-based APC resistance assay (Gradipore PC Impedance Test) to a routinely utilized commercial APTT based assay (Coatest APC Resistance Assay). The DRVV based assay offers improved sensitivity and specificity for the factor V Leiden mutation. However, the routine use of both assays provides optimum reliability for diagnosis of genetic APC resistance. Our results suggest that when both tests are either positive or negative, DNA analysis is unnecessary. Interference by lupus anticoagulants is dramatically minimized by the phospholipid rich DRVV reagent used in the assay and it is insensitive to high factor VIII activity. Additionally, discrepant functional assay results allow identification of patients who may have an acquired APC resistant phenotype.
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PMID:The use of two different APC resistance assay systems provides optimal sensitivity and specificity for diagnosing genetic APC resistance. 928 90

It is well known that thalassemic patients exhibit an increased frequency of thrombotic events. Most individuals with resistance to activated protein C (APCR) are the result of a point mutation replacing Arg 506 with Gln in the factor V aminoacidic sequence (factor V Leiden). Recently APCR has been shown to account for up to 50% of cases of thrombophilia. In this report, we describe a 10 year old thalassemic intermedia patient heterozygous for Factor V R506Q who developed a stroke following transfusion. Coagulation laboratory values were all within the normal range and there was no evidence of a lupus anticoagulant. Computerized brain tomography showed an ischemic area in the left temporo-parietal region. At follow-up, plasma from the patient demonstrated APCR and molecular diagnostic testing revealed heterozygosity for factor V R506Q. We suggest that the heterozygosity for factor V Leiden could increase the thrombotic risk in thalassemia intermedia. We believe it may be beneficial to screen all intermedia thalassemic patients for APCR especially before starting a transfusional regimen.
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PMID:Resistance to activated protein C as a risk factor of stroke in a thalassemic patient. 949 70


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