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)

Thrombosis is a major clinical feature of the antiphospholipid syndrome. Interactions between genetic and acquired factors could contribute to thrombosis development. In this study, we evaluated 40 patients with antiphospholipid syndrome and thrombosis, 31 primary and nine secondary to systemic lupus erythemathosus, to estimate the carrier rates of factor V Leiden, 20210A --> G prothrombin variant and 677C --> T in the MTHFR gene. Protein C, protein S and antithrombin were measured in 30 patients, with a median of 100.66 +/- 23.86, 93.57 +/- 36.44 and 98.8 +/- 5.67%, respectively. None of the patients were deficient on these natural anticoagulants. No significant variation was found between the patient group and the controls, regarding the prevalence of homozygotes for the mutated 677T allele (2.5 versus 5.4%), or heterozygotes for factor V Leiden (0 versus 0.7%). Despite the fact that these mutations are relatively common in Brazilian thrombophilic patients, its low prevalence in this cohort of patients suggest that these genetic alterations are not risk factors for thrombosis in antiphospholipid syndrome. The prevalence of the mutated allele 20210A of the prothrombin gene was higher in patients when compared with controls (5 versus 0.7%; P = 0.01), suggesting that prothrombin variant could increase the risk of thrombosis in patients with antiphospholipid syndrome.
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PMID:The impact of the search for thrombophilia risk factors among antiphospholipid syndrome patients with thrombosis. 1108 90

Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97:844-849)
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PMID:Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus. 1115 6

In the present study, a new functional test for the detection of increased resistance of coagulation factor V to degradation by activated protein C (factor V Leiden mutation) was evaluated. The STA-STACLOT APC-R Test (Diagnostica Stago, Asnieres, France) is based on the specific activation of factor X by Crotalus viridis helleri snake venom. The results are given as clotting time in seconds of the patient's plasma in the presence of venom and activated protein C. The intra-assay coefficient of variation was 2.17% (n=20) for samples within the normal range, and 1.70% and 1.42% (n=20) for the plasma of a heterozygous or a homozygous carrier of the factor V Leiden mutation, respectively. The inter-assay coefficient of variation (n=10) was 7.75% for the plasma of a healthy donor, 5.05% for the plasma of a heterozygous carrier and 3.38% for the plasma of a homozygous individual. The normal range (5th-95th percentile) of 136.4 s-174.7 s was derived from the clotting time of the plasma of 38 healthy controls. Values below 136 s were found in every sample from patients carrying the factor V Leiden mutation (n=52), whereas no patient with protein C (n=11) or protein S deficiency (n=10) had reduced clotting times. Homozygous carriers of the factor V Leiden mutation had clotting times shorter than 66.0 s and heterozygous carriers had clotting times longer than 80.0 s. Thus, based upon the individual clotting time, patients homozygous for factor V Leiden mutation could easily be distinguished from normals or heterozygous individuals. The influence of coagulation factor X, V, or II deficiency on the STACLOT APC-R Test was evaluated and revealed prolonged clotting times at factor V activities below 50%. In the presence of lupus anticoagulant the specificity of the STA-STACLOT APC-R Test was clearly decreased. In the present study, we clearly show that the STA-STACLOT APC-R Test is able to discriminate carriers of the factor V Leiden mutation from healthy controls or patients with protein C or protein S deficiency.
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PMID:Evaluation of a highly specific functional test for the detection of factor V Leiden. 1119 68

The association of thrombophilia and obstetrical complications is documented and well consistent with the hypothesis of an insufficient placental perfusion due to fibrin deposition as a major underlying pathophysiological mechanism. Factor V Leiden is one of the most frequent thrombophilic mutations. A high prevalence of this mutation has recently been reported in a group of 21 German women with haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. In this respect, we studied the prevalence of factor V Leiden in 18 women who were consecutively diagnosed at our Department of Obstetrics and Gynaecology as having HELLP syndrome, between 1995 and 1999. Women were tested either at the time of diagnosis or months or years after delivery for coagulation parameters, protein C (PC), protein S (PS), antithrombin III, lupus-like anticoagulant, anticardiolipin antibodies (ACA), activated protein C (APC) resistance and detection of the G1691A mutation (factor V Leiden). In all women, the parameters studied were normal and in none of the investigated cases was the G1691A mutation found. HELLP being a severe form of preeclampsia, we think that the reported association between factor V Leiden and HELLP may reflect the well-known association with preeclampsia.
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PMID:HELLP syndrome and factor V Leiden. 1126 21

The goal of this article is to study the association of known markers of thrombophilia with venous thrombosis in young patients (< 45 years) from the Western part of India. A prospective study of 432 patients (252 males and 180 females, age 1-45 years) was conducted between 1994 and 2000 (6 years). The diagnosis was confirmed in all the patients by ultrasound with Doppler or by a computed tomograph (CT) scan of the brain with or without contrast depending on the case. Detailed clinical examination, and family history was taken to establish recurrent thrombosis and familial occurrence of thrombosis. The markers studied were protein C, protein S, antithrombin (AT) III, factor V Leiden mutation, prothrombin gene G20210A polymorphism, and the thermolabile MTHFR variant C677T polymorphism, using appropriate techniques. Lupus inhibitor was tested in the first 72 patients using Dilute Russel Viper Venom Time (DRVVT) test, and anticardiolipin antibodies were tested by enzyme-linked immunosorbent assay. Protein C, protein S, and AT III deficiency was detected in 9.5%, 6.5%, and 2.6%, respectively, among the patients. Anticardiolipin antibody was present in 9.9% of the patients, whereas lupus anticoagulant was present in 8.3% of patients; factor V Leiden mutation was detected in 3% of patients; thermolabile variant of MTHFR C677T polymorphism was present in 14.9% of patients with 1.2% homozygotes. Prothrombin G20210A polymorphism was not detected in any sample in this population. One hundred and four patients of 432 (24.9%) had recurrent attacks of thrombosis without any proximate precipitating cause, whereas 7.5 % of the patients had another close member of the family with a history of deep venous thrombosis. Eighty-six members from 28 families (out of 32 families giving family history of thrombosis) were investigated and found to have protein C and protein S deficiency in seven each; factor V Leiden was present in 6, and MTHFR C677T polymorphism was present in 5 cases. Hence, 25 of 86 members (28%) from the family of patients with familial history deep venous thrombosis had positive markers for thrombophilia. Thus, we could show that in young patients presenting with thrombosis, at least 34% of them had a demonstrable cause for thrombophilia. Prothrombin gene polymorphism G20210A seems to be nonexistent in our population and AT III deficiency also appears to be low compared to other markers of thrombophilia. There is a high prevalence of variant MTHFR C677T in our series, but the incidence of MTHFR C677T in our general population is also high. Hence, the significance of this finding in our cases of deep venous thrombosis remains to be seen, but we did not see any homozygotes when we tested 70 randomly selected asymptomatic persons, whereas in the present series, 1.8% of the patients had homozygosity for the MTHFR C677T polymorphism.
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PMID:Venous thromboembolism in young patients from western India: a study. 1129 95

In 70% to 80% of patients with venous thromboembolism, a thrombophilic defect can be identified. The most important defects are: antibodies to phospholipids or lupus anticoagulants, mutation of factor V Leiden, prothrombin mutation, mild hyperhomocysteinaemia, and increased factor VIII levels. Deficiencies of antithrombin, protein C or protein S are rare. Whether or not screening for thrombophilia in patients with idiopathic venous thromboembolism is justified, depends on the potential benefits for the patients, or their relatives. At present, patients with a thrombophilic defect do not appear to have a much higher risk for recurrent venous thromboembolism, than patients with thrombosis but without a defect. The absolute risks of venous thromboembolism in asymptomatic relatives with a thrombophilic defect are too low to justify initiating a general policy of family screening. In conclusion, a conservative approach towards thrombophilia screening in idiopathic venous thromboembolism is warranted.
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PMID:[No indication for thrombophilia screening in patients with idiopathic venous thromboembolism and their relatives]. 1141 64

The G20210A mutation of the prothrombin (PT) gene has recently been identified as a risk factor for venous thromboembolism (VTE). This mutation was shown to be present mainly among Caucasian populations, with a higher frequency in southern than in northern Europe. The aim of our study was to determine the prevalence of the PT 20210A allele in the Polish general population and in patients with a history of venous thrombosis. The patient group comprised 323 subjects with VTE before the age of 45, recurrent VTE or thrombosis in an unusual site. The control group consisted of 399 healthy individuals. Heterozygosity for the PT 20210A allele was found in 21 (6.5%) patients and 7 (1.8%) controls. In 7 (33.3%) of the 21 heterozygous patients the PT 20210A allele was associated with the factor V Leiden mutation, in 1--with the homozygous C677T mutation of the methylenetetrahydrofolate reductase (MTHFR), and in 1--with lupus anticoagulant. Our results indicate that the presence of the 20210A allele is a mild risk factor for venous thrombosis if not associated with other thrombophilic defect (odds ratio 2.2; 95% CI: 0.8-5.5). The risk is greater in double heterozygous carriers of the PT 20210A allele and factor V Leiden mutation.
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PMID:[Prevalence of G20210A prothrombin gene mutation in Poland]. 1143 83

Until recently, laboratory diagnosis of thrombophilia was based on investigation of the plasmatic anticoagulant pathways to detect antithrombin, protein C, and protein S deficiencies and on the search for dysfibrinogenemia and anti-phospholipid antibodies/lupus anticoagulants. More recently, laboratory investigations have been expanded to include activated protein C (APC) resistance, attributable or not to the presence of the factor V Leiden mutation; hyperprothrombinemia attributable to the presence of the prothrombin gene mutation G20210A; and hyperhomocysteinemia attributable to impairment of the relevant metabolic pathway because of enzymatic and/or vitamin deficiencies. All of the above are established congenital or acquired conditions associated with an increased risk of venous and, more rarely, arterial thrombosis. Testing is recommended for patients who have a history of venous thrombosis and should be extended to their first-degree family members. Because most of the tests are not reliable during anticoagulation, it is preferable to postpone laboratory testing until after discontinuation of treatment. Whenever possible, testing should be performed by means of functional assays. DNA analysis is required for the prothrombin gene mutation G20210A. Laboratory diagnosis for anti-phospholipid antibodies/lupus anticoagulant should be performed by a combination of tests, including phospholipid-dependent clotting assays and solid-phase anti-cardiolipin antibodies. Hyperhomocysteinemia can be diagnosed by HPLC methods or by fluorescence polarization immunoassays.
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PMID:Laboratory investigation of thrombophilia. 1151 92

The two most common hereditary risk factors for thrombosis are factor V Leiden mutation and a prothrombin gene mutation. There is indeed a thrombotic tendency in patients with systemic lupus erythematosis (SLE) and it is not always associated with antiphospholipid antibodies. We aimed to determine the relationship between both factor V Leiden and prothrombin gene mutations and SLE. Using polymerase chain reaction (PCR) the factor V Leiden and prothrombin gene mutations were evaluated in 55 patients (20 children and 35 adults) with SLE. Although seven patients were found to have factor V Leiden mutation in the heterozygous state, two had the heterozygous G-->A (20210) prothrombin gene mutation. Although one had these two mutations concurrently, these two patients did not have thrombosis. The factor V Leiden mutation frequency (12.7%) was higher than that of our general population (7.1%). On the other hand, seven of the patients with SLE had a thrombotic event. Although of these seven, four (57%) had factor V Leiden mutation, three (43%) had no mutation. Of 48 patients with no thrombotic history, only three had the factor V mutation (6.25%). The prevalence of the factor V Leiden mutation in SLE patients with and without thrombosis was significantly different by Fisher's exact test (p<0.05). The risk of venous thrombosis in patients with factor V Leiden increased threefold compared to that in those without factor V Leiden mutation (odds ratio 20.1; CI 2.99-133.6). Although factor V Leiden mutation seems to play a role in the development of venous thrombosis in SLE, the development of thrombosis in SLE is multifactorial.
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PMID:Survey of factor V leiden and prothrombin gene mutations in systemic lupus erythematosus. 1152 32

The association of thrombophilia with pregnancy complications has received increasing attention. It is now apparent that thrombophilia is responsible for a large number of the serious complications of pregnancy such as venous thrombosis, pulmonary embolism, fetal loss, pregnancy loss, intrauterine fetal demise, and preeclampsia. The inherited thrombophilia abnormalities, factor V Leiden mutation, prothrombin gene mutation 20210A, and antithrombin III, protein C, and protein S deficiency, and the acquired disorders, the anticardiolipin syndrome and lupus inhibitor, are responsible for a large share of the incidences of premature termination of pregnancy and many of the above complications. The normal physiology of pregnancy may be prothrombotic, with evidence for increased markers of activated coagulation and coagulation factors. There is a decrease in protein S and resistance to activated protein C occurs in a significant number of pregnancies in the absence of the factor V Leiden mutation. In the following article, we review some of the major studies that have correlated the thrombophilia and other acquired disorders that adversely impact pregnancies.
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PMID:Thrombophilia and pregnancy: review of the literature and some original data. 1169 6


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