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)

BACKGROUND: Thrombophilia may be associated with premature atherosclerosis, an increased susceptibility to primary arterial thrombosis and an increased failure rate for peripheral vascular or endovascular interventions. The aim of this study was to determine the prevalence of thrombophilia in patients with intermittent claudication (IC). METHODS: This was a prospective study of 116 consecutive new patients (70 men; median age 65 (range 43-84) years) referred to this regional vascular surgery unit with IC. Patients on warfarin, or who had previously undergone lower limb reconstruction and/or angioplasty, were excluded. RESULTS: Thrombophilia was demonstrated in 24 patients (21 per cent). The commonest abnormality (15 patients, 13 per cent) was a raised level of anticardiolipin antibody (ACLA) (11 immunoglobulin (Ig) M, four IgG). Other abnormalities comprised: lupus anticoagulant (one), protein C deficiency (two), protein S deficiency (two), activated protein C resistance (one) and factor V Leiden heterozygosity (three). All abnormalities were confirmed on repeat testing. No patient had a history of venous thrombosis. There was no statistically significant relationship between ACLA status and age, sex, ankle : brachial pressure index, previous myocardial infarction or stroke, previous carotid endarterectomy or coronary artery surgery, serum cholesterol, current use of antiplatelet agents or current smoking status. CONCLUSION: Almost one-quarter of new patients referred to this regional vascular unit with IC have thrombophilia; over half of those affected have a raised ACLA level compatible with the antiphospholipid syndrome. At present, the clinical significance and management implications of these abnormalities remain unknown.
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PMID:Vascular surgical society of great britain and ireland: prevalence and significance of thrombophilia in patients with intermittent claudication 1036 36

We describe a case of a 28-year-old man who developed an extensive spontaneous deep venous thrombosis. Testing revealed heterozygotic factor V Leiden mutation, and the presence of both lupus anticoagulant (LA) and elevated IgM anticardiolipin antibody (ACA). Several family members were found to be heterozygous for factor V Leiden. A paternal aunt had the factor V Leiden mutation, an elevated plasma homocysteine and a borderline increased IgG ACA level. No other family member had a history of a venous thrombotic event. This case illustrates that evaluation of young patients who present with venous thrombosis should be performed for both hereditary and acquired thrombophilic defects. The family studies suggest that the presence of a lupus anticoagulant may be more clinically significant than elevated ACA in risk assessment. Although screening family members when the proband carries factor V Leiden is controversial, psychological reassurance of those who test negative and simple advice on occupations or social habits (e.g., smoking) for those who test positive may be important benefits.
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PMID:Spontaneous venous thrombosis in a young patient with combined factor V Leiden and lupus anticoagulant. 1046 79

A method for detecting activated protein C (APC)-resistant factor V, especially factor V Leiden, is described, which uses reagents containing two unfractionated snake venoms. The procedure can be used for testing plasma samples from patients receiving oral anticoagulant therapy, heparin therapy and patients with lupus anticoagulant, and does not require the use of factor-V-deficient plasma. The sample plasma is first incubated with dilute venom from Agkistrodon contortrix contortrix (Southern Copperhead) which activates the endogenous protein C and then a dilute Russell's viper venom time test is performed. In individuals with APC-resistant factor V, especially factor V Leiden, a marginal prolongation of dilute Russell's viper venom time was noted [1.14 +/- 0.14 s (n = 16)]. Non-carriers were easily discriminated in each patient group, with a prolongation of 2.69 +/- 0.30 s for normal blood donors (n = 127), 2.61 +/- 0.38 s for patients taking oral anticoagulants (n = 102), 2.41 +/- 0.45 s for patients taking heparin (n = 96), and 2.38 +/- 0.41 s for patients with lupus anticoagulant (n = 22). Patients taking oral anticoagulants with moderate prolongation (between 1.5- and 2.0-fold) may have low levels of functional protein C and this might additionally indicate a subgroup of such patients at higher than normal thrombotic risk.
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PMID:Detecting APC-resistant factor V: a functional method without plasma dilution. 1049 17

In a whole year from July 1997 to June 1998, a total of 50 patients with sonogram-proved venous thrombosis who called on our hematology clinic consecutively entered into the study. Their mean age was 59.1 +/- 17.5 years, range 18-83 years, and 29 were male. A series of examinations were performed in order to find out the cause of venous thrombosis. These examinations included antithrombin, protein C, protein S, plasminogen, heparin cofactor II, activated protein C ratio, factor V Leiden mutation, fibrinogen, factors VIII and XII, euglobulin lysis time, 677 C-->T mutation of methylenetetrahydrofolate reductase (MTHFR), prothrombin 20210 (PT 20210) A allele mutation, lupus anticoagulant, anticardiolipin antibody, and complete blood count. Five patients (10%) were found to have malignancy; an inferior vena cava thrombosis in one patient was due to venous compression by hydronephrosis; two patients had lupus anticoagulant; two had varicose veins of legs; two had protein C deficiency; four had protein S deficiency; two had plasminogen deficiency; two had antithrombin deficiency. No activated protein C resistance, elevated factor VIII level, factor V Leiden, PT 20210 A allele or heparin cofactor II deficiency was found in the present study. Homozygous MTHFR 677 C-->T gene mutation was found in 7 patients (14%); one of them also had a plasminogen deficiency. No possible risk factor of venous thrombosis could be found in 24 patients (48%). In conclusion, malignancy and protein S deficiency were the most frequent acquired and congenital causes of venous thrombosis in the Chinese, respectively.
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PMID:Causes of venous thrombosis in fifty Chinese patients. 1062 72

One of the causes of portal hypertension is portal vein thrombosis (PVT). The aim of this study was to determine whether natural anticoagulant deficiencies, activated protein C resistance (APCR), and factor V Leiden play a role in the development of PVT, leading to cavernous transformation of the portal vein (CTPV). Twenty-three patients with idiopathic CTPV (group 1) seen at Hacettepe University Hospital during the past 12 years were identified and prospectively studied. These 23 patients underwent a detailed hematological evaluation including measurement of protein S, protein C, antithrombin III, activated protein C resistance (APCR), and factor V Leiden gene mutation. Additionally, all patients were tested for anticardiolipin antibodies (ACA), IgG, IgM, and lupus anticoagulant (LA). Natural anticoagulants and APCR were measured using available commercial kits, and factor V Leiden mutation (R506Q) was detected by Mnl I digestion of an amplified factor V DNA fragment. All parameters were measured at least 6 months after the diagnosis of CTPV was established. No patient was on anticoagulant or antiaggregant treatment while tested. The findings in these 23 patients were compared with those in 20 healthy control subjects (group 2), in whom all tests mentioned above were also performed. In 23 patients (group 1), who had no recognizable factor for portal vein thrombosis, considerably natural anticoagulant deficiencies and factor V Leiden mutation positivity were found when we compare them to those healthy controls (group 2). The protein C levels of six patients (26%), the protein S levels of 10 patients (43.5%), and the antithrombin III levels of five patients (26%) were lower than in control subjects. Two patients were found to have combined protein S and antithrombin III deficiency, and one had combined protein S and C deficiency and APCR. APCR was detected in seven of the 23 patients, and six of these seven patients were found to have R506Q factor V Leiden mutations. In group 1, ACA IgG levels were higher in four patients (17%) and ACA IgM level was higher in one (4%) compared with the control group. LA was positive in only one patient in group 1. Natural anticoagulant deficiencies and factor V Leiden mutation are strongly associated with PVT. The natural anticoagulant deficiencies and APCR (almost totally caused by R506Q mutation) produce a favorable medium for thrombus generation. PVT seems to be related to the natural anticoagulant deficiencies and factor V Leiden R506Q mutation. A combination of these defects increases the incidence of PVT and these factors should be evaluated carefully in patients with idiopathic CTPV.
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PMID:The role of natural anticoagulant deficiencies and factor V Leiden in the development of idiopathic portal vein thrombosis. 1063 14

Markers of thrombotic risk--fibrinogen, factor VIII and immunoglobulin G (IgG) anticardiolipin titres--were measured, and the presence of lupus anticoagulant and factor V Leiden were assessed in 84 patients with a solid or haematological malignancy. These patients were monitored, following the insertion of an indwelling venous catheter, for thrombosis. Fifty-five were given prophylactic low-dose warfarin. Over a mean of 15 weeks there were 10 (12%) thrombotic events in 10 patients. Seven were on warfarin. Haemorrhagic problems occurred in three (5%), all on warfarin. Of the 84 patients, 86% had raised fibrinogen levels, 37% elevated factor VIII and 44% raised anticardiolipin levels. Lupus anticoagulant was present in five and three were heterozygous for factor V Leiden. A high prevalence of a range of prothrombotic changes was confirmed and the frequent presence of low-titre anticardiolipin antibody in subjects with malignancy demonstrated. However, none of these parameters predicted the development of thrombosis (P > 0.05).
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PMID:Thrombosis, markers of thrombotic risk, indwelling central venous catheters and antithrombotic prophylaxis using low-dose warfarin in subjects with malignant disease. 1064 78

We studied the prevalence and the effect of coagulation factor V Leiden mutation on the occurrence of thrombotic episodes in 120 Hungarian patients having systemic lupus erythematosus (SLE) with or without antiphospholipid antibody. The frequency of the factor V Leiden mutation in Hungarian SLE patients was 13%, which is comparable with those found previously in a healthy Caucasian population. The incidence of venous thrombosis among factor V Leiden carriers has been found to be higher (odds ratio [OR] 1.7) than it is in patients without Leiden mutation (38% vs 29%). In addition, the frequency of venous thrombosis in the heterozygous SLE patients (OR 8.4 [confidence interval (CI) 0.8-83.9] P = 0.06) is dependent on the coexistence of other risk factors, such as antiphospholipid antibody. Moreover, among heterozygous factor V SLE patients, the Leiden mutation could explain the tendency to have significantly higher prevalence of fetal losses (OR 3.9 [CI 1.2-12.0] P = 0.02) and higher prevalence of cerebrovascular lesions, cardiac valvular abnormalities, and Raynaud's syndrome than that found in individuals without factor V Leiden mutation of those having antiphospholipid antibody. Systemic lupus erythematosus patients with combined defects suffer more severely from thrombosis than those with a single risk factor do, suggesting that thrombophilia is a multifactorial disorder in SLE, also. Although, the factor V Leiden mutation does not seem to be a significant risk factor for venous thrombosis in SLE, these data demonstrate that Leiden mutation can be regarded as an additive thrombogenic factor providing higher predisposition to several vasoocclusive disorders in SLE.
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PMID:The Leiden mutation of coagulation factor V in Hungarian SLE patients. 1072 48

Although first-time miscarriages are usually caused by chromosomal defects, about 55% of recurrent miscarriages are caused by procoagulant defects that induce thrombosis and infarction of placental vessels. Of recurrent miscarriages, about 7% are caused by chromosome defects, 15% to hormonal defects, and 10% to 15% to anatomical defects. Recurrent miscarriage involves more than 500,000 women in the United States each year. During the past 4 years, 179 patients, prescreened for chromosomal, hormonal, and anatomical defects, and found to harbor none, underwent hemostasis defect evaluation. A total of 160 of these have been analyzed. A hemostasis defect was found in 150 of 160 women (n = 94% of screened women). The mean age was 33 years; the mean number of miscarriages before referral was three. All women with a procoagulant defect (149) were treated with preconception ASA at 81 mg/d, and unfractionated porcine heparin at 5000 U every 12 hours was added immediately postconception; both agents were used to term delivery. Only two of 149 patients failed therapy. The defects found were as follows: antiphospholipid syndrome, 67%; sticky platelet syndrome, 21%; tissue plasminogen activator (TPA) deficiency, 9%; factor V Leiden, 7%; high PAI-1, 6%; protein S, 5%; high LP(a), 3%; AT, 2%; protein C, 1%. Thirty-eight patients had more than one defect. In the group with antiphospholipid syndrome, 24% only had a subgroup antibody (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol) or antiphosphatidic acid antibody, in the absence of anticardiolipin antibody or lupus anticoagulant. This finding is similar to that recently reported in early age ischemic stroke patients (<50 years old). In summary, about 55% of patients with recurrent miscarriage harbor a procoagulant defect to account for placental vascular occlusion. More than 98% will have a normal term delivery with preconception aspirin (ASA) and addition of postconception heparin to term. Patients should be screened by an obstetrician or by reproductive specialists for hormonal and anatomic defects before initiating a procoagulant evaluation; if such prescreening is done, the yield of a defect is high and appropriate therapy leads to an excellent outcome.
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PMID:Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects: prevalence, treatment and outcome results. DRW Metroplex Recurrent Miscarriage Syndrome Cooperative Group. 1089 70

We examined the relationship between placental histology and thrombophilia status in women who were admitted with severe pre-eclampsia/eclampsia, placental abruption, intrauterine growth restriction or unexplained stillbirth. All women had thrombophilia screen at least 10 weeks after delivery (antithrombin III, protein C, protein S, activated protein C resistance, anticardiolipin antibodies, lupus anticoagulant, fasting plasma homocysteine and specific mutations to methylenetetrahydrofolate reductase C677T, G20210A prothrombin gene and factor V Leiden. Placental histology reports were examined to identify the frequency of thrombotic lesions in the placenta including fetal stem vessel thrombosis, fetal thrombotic vasculopathy, placental infarction, perivillous fibrin deposition, intervillous thrombosis and placental floor infarction. During a 17 month period, a cohort of 79 women met the study criteria. Thirty (70%) out of 43 women with abnormal thrombophilia screen had abnormal placental histology. Twenty-eight (78%) out of 36 women with negative thrombophilia screen had abnormal placentae. No specific histological pattern could be identified when thrombophilia positive and thrombophilia negative groups were compared. We propose that there is a poor correlation between thrombophilia status and pathological changes of the placenta in women with severe pregnancy complications.
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PMID:Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? 1115 44

Clotting-based activated protein C (APC) assays have limitations when testing patients on oral anticoagulant (OA) therapy or with a lupus anticoagulant (LA). Predilution in factor V (FV)-deficient plasma and testing with phospholipid-rich Russell Viper venom (RVV)-based methods have been shown to be the most suitable methods when testing these patient groups, respectively. We evaluated a modified RVV based clotting test (Gradileiden V test; Gradipore, Sydney, Australia) in a large patient cohort and determined its sensitivity to the FV Leiden mutation. We also examined whether normal plasma can be used to dilute plasma from warfarinized patients without compromising sensitivity to the FV Leiden mutation. A total of 1,956 plasmas were studied including congenital protein C (five plasmas), and protein S deficiency (five plasmas), LA (29 plasmas), FV Leiden heterozygote (102 plasmas), and homozygote (five plasmas), warfarin (54 plasmas), standard heparin therapy (37 plasmas) and normal healthy controls (21 plasmas). Molecular analysis was performed on all samples. The effect of FV Leiden concentration on the APC ratio was examined by determining the APC resistance of a homozygous plasma serially diluted in six sources of normal plasma (NP). The relationship was non-linear and dependent on the initial APC ratio of the chosen source of NP. APC resistance was demonstrated in the varying sources of NP in dilutions of 1/4 (25% FV Leiden) to 1/32 (3% FV Leiden). A 1/2 dilution in pooled NP is recommended for patients on OA therapy because the test remains sensitive at levels of 25% FV Leiden and this is the dilution routinely used for other applications in a coagulation laboratory. The effect of a LA on the APC ratio was similarly studied by determining the APC resistance of a homozygous plasma serially diluted in two sources of LA-positive plasma. This relationship was also non-linear and dependent on the initial APC ratio of the LA-positive plasma. APC resistance was demonstrated in dilutions of 1/16 (6% FV Leiden) to 1/64 (1.5% FV Leiden) demonstrating the sensitivity of the test to APC resistance in the presence of a LA. Our results show the modified RVV-based test clearly predicts the presence of factor V Leiden in a large cohort of patients. The method offers advantages when testing patients with a LA and patients receiving warfarin providing a 1/2 predilution step in pooled NP is performed. Pooled NP does not affect the sensitivity of the test to the mutation, is routinely used in coagulation laboratories, and is considerably less expensive than FV-deficient plasma.
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PMID:Determination of activated protein C resistance in anticoagulated and lupus positive patients. 1093 5


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