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)

Thrombophilia is characterized by clinical tendency to thrombosis or molecular abnomalities of hemostasis that predisposes to thromboembolic disease. Hereditary thrombophilia may be due to antithrombin deficiency, or protein C or protein S deficiency. More recently, other molecular abnormalities have been described: activated protein C resistance due to factor V Leiden, G 20210 A polymorphism on the prothrombin gene, increased factor VIII plasma levels or hyperhomocysteinemia. Acquired thrombophilia is frequently associated with the antiphospholipid syndrome characterized by thrombosis and presence of lupus anticoagulant or phospholipid-binding antibodies. In some cases, no molecular abnormality is found despite recurrent thrombosis observed in patient and his/her family. This situation can be considered as clinical thrombophilia.
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PMID:[Definition of thrombophilia]. 1502 78

Thrombophilia can be defined as an increased tendency to thrombosis. There are several defined risk factors for thrombosis, and these are generally separated into acquired and congenital factors. Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, protein C and protein S, and genetic polymorphisms such as prothrombin G20210A and the cleavage-resistant factor mutation, factor V Leiden, which leads to a condition known as activated protein C resistance. Acquired risk factors include antiphospholipid antibodies, detected as lupus anticoagulants, and/or anticardiolipin or anti-beta2-glycoprotein I antibodies. Elevated homocysteine, immobility, increasing age, surgery, cancer, poor nutrition, pregnancy, high levels of clotting factors, and use of oral contraceptives and hormone replacement therapy comprise other risk factors. Each of these constitutes an element of increased risk, which is compounded when concomitant. There is ongoing debate regarding relative and compound risks, the value of laboratory screening, whom to screen for with these markers, and the form and duration of clinical management. This report briefly explores, from a scientist's perspective, some important issues that are sometimes overlooked.
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PMID:Diagnostic issues in thrombophilia: a laboratory scientist's view. 1570 70

The quality control process is a critical feature of pathology best practice. In addition to internal quality control processes applied on a test-to-test or day-to-day basis, the participation of laboratories in external quality assurance programs (QAPs) is critical to achieving ongoing test accuracy. There are several such programs operating in the international arena. With respect to thrombophilia, these include the Australia-based Royal College of Pathologists of Australia QAP, the United Kingdom-based National External Quality Assessment Service, and the International Thrombophilia External Quality Assessment Scheme, based in the Netherlands. Although there are some similarities between the programs, some diversity is also apparent. Each of the programs assess for the common markers of congenital thrombophilia, such as antithrombin, protein C, protein S, and activated protein C resistance. Testing of some acquired markers of thrombophilia, such as lupus anticoagulant, and genetic tests such as factor V Leiden and prothrombin G20210A mutation, are also available. This report focuses on some recent trends from these programs.
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PMID:Learning from peer assessment: the role of the external quality assurance multilaboratory thrombophilia test process. 1570 79

We have determined lupus anticoagulants, anti-beta2 glycoprotein I (beta2GPI) and antiprothrombin antibodies in the Leiden Thrombophilia Study, a population-based case-control study designed to determine risk factors for deep venous thrombosis (DVT). Lupus anticoagulant (LAC) was measured in 473 patients and 472 control subjects. Four control subjects (0.9%) and 14 patients (3.1%) had a positive LAC, resulting in a 3.6-fold increased risk [odds ratio (OR) 3.6, 95% CI: 1.2-10.9]. Of the total population, 49 were positive for anti-beta2GPI antibodies: 15 controls (3.4%) and 34 patients (7.5%), implying a 2.4-fold increased risk (95% CI: 1.3-4.2). Antiprothrombin antibodies were present in 114 subjects: 48 controls (11.0%) and 66 cases (14.6%) with an OR of 1.4 (95% CI: 1.0-2.1). When LAC was considered in the co-presence of antiprothrombin or anti-beta2GPI antibodies the OR increased to 10.1 (95% CI: 1.3-79.8). A LAC without a positive anti-beta2GPI or antiprothrombin test was not associated with a risk for DVT (OR 1.3, 95% CI: 0.3-6.0). This study demonstrates that the presence of LAC, anti-beta2GPI antibodies and antiprothrombin antibodies are risk factors for DVT in a general population. The strongest association holds for the combination LAC and the presence of anti-beta2GPI or antiprothrombin antibodies.
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PMID:Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. 1610 5

The role of thrombophilia in the pathogenesis of preeclampsia is controversial. The aim of this case-controlled study was to determine whether thrombophilia increases the risk of preeclampsia or interferes with its clinical course. A total of 808 white patients who developed preeclampsia (cases) and 808 women with previous uneventful pregnancies (controls) matched for age and parity were evaluated for inherited and acquired thrombophilia (factor V Leiden; factor II G20210A; methylenetetrahydrofolate reductase C677T; protein S, protein C, and antithrombin III deficiency; anticardiolipin antibodies; lupus anticoagulant; and hyperhomocysteinemia). Odds ratios (ORs) with 95% confidence intervals (CIs) for risk of being carriers of thrombophilia in cases compared with controls and for risk of maternal life-threatening complications and adverse perinatal outcomes in preeclamptic patients with or without thrombophilia were calculated. Women with severe preeclampsia (406 cases) had a higher risk (OR, 4.9; 95% CI, 3.5 to 6.9) of being carriers of either an inherited or acquired thrombophilic factor, except for protein S, protein C, and antithrombin deficiency. In women with mild preeclampsia (402 cases), only prothrombin and homozygous methylenetetrahydrofolate reductase gene mutations were significantly more prevalent than in the controls. Thrombophilic patients with severe preeclampsia are at increased risk of acute renal failure (OR, 1.8; 95% CI, 1.5 to 2.2), disseminated intravascular coagulation (OR, 2.7; 95% CI, 1.1 to 6.4), abruptio placentae (OR, 2.6; 95% CI, 1.2 to 6.0) and perinatal mortality (OR, 1.7; 95% CI, 1.5 to 2.2) compared with nonthrombophilic preeclamptic patients. Our study demonstrates a significant association between maternal thrombophilia and severe preeclampsia in white women. Thrombophilia also augments the risk of life-threatening maternal complications and adverse perinatal outcomes in preeclamptic patients.
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PMID:Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study. 1628 82

To evaluate the utilization of thrombophilia screening at a large urban academic tertiary care center, we retrospectively examined the indications, appropriateness, and results of 200 consecutive thrombophilia panels. Of the panels, 103 (51.5%) were ordered for venous thromboembolism; 124 (62.0%) were ordered during acute thrombotic episodes, and at least 40 (20.0%) had abnormal protein C and S results, of which 25 (63%) were attributable to anticoagulation and the remainder to pregnancy. Of the 200 panels, 46 (23.0%) had a significant abnormality; the most common abnormal result was a lupus anticoagulant, occurring in 23 cases (11.3%). Thrombophilia screening seems to be overutilized in our population, especially considering that the majority of tests are ordered during suboptimal conditions, eg, acute thrombosis, pregnancy, or anticoagulation. At present, outside the research setting, thrombophilia panels should be reserved for special circumstances, targeted to factors for which there would be a specific clinical impact, and performed in the absence of confounding clinical variables.
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PMID:An evaluation of thrombophilia screening in an urban tertiary care medical center: A "real world" experience. 1675 92

Thrombophilia these days is a subject of many medical research including obstetric and gynecology where causing feto-maternal complications. In women predispose to venous thromboembolism in high risk situation like pregnancy, puerperium, operation, prolonged bed rest or hormonal treatment. For fetal complication account miscarriages, intrauterine deaths, IUGR, and for maternal account premature placental separation and severe preeclampsia. Diagnostic panel include inherited factors like factor V Leiden and prothrombin mutation, activated protein C resistance and acquired like anticardiolipin antibodies, antibodies against beta2-glicoprotein 1 and lupus anticoagulant. The aim of this paper is estimation ofthrombophilia as a causative factor of pregnancy complications and attempt to establish screening criteria for thrombophilia. Material involved 36 women with pregnancy complications divided into three groups correlating with trimester when pregnancy loss occured. All patients had genetic, hormonal and anatomic tests done on purpose to exclude other possible causes of miscarriages. All women had done both types of tests for inherited and acquired thrombophilia. For factor V and II gene polimorphism we used PCR and RLFP method. Acquired protein C resistance and lupus anticoagulant was tested using chronometric method with the use of time measurement of optical density accompanying coagulation. Anticardiolipin antibodies and antibodies against beta2-glicoprotien 1 were measured in ELISA tests. Our current results present the frequency of at least one thrombophilic factor in 16.6% patients. The highest frequency rate was observed among women with pregnancy loss between 7th and 12th gestational week--19.04%. In this group we also noticed the highest number of miscarriages. In remaining two groups, with pregnancy loss between 12th and 22nd and after 22nd gestational week, one case of thrombophilia occurred in each group.
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PMID:[Frequency of antiphospholipid antibodies and factor V (G1691A), prothrombin (G20210A) gene polimorphism among women with pregnancy complications]. 1719 54

Regular multilaboratory surveys of laboratories by the Royal College of Pathologists of Australasia Quality Assurance Program (QAP) have been conducted to assess proficiency in tests of hemostasis for the last 40 years. This article focuses primarily on specialized assays of hemostasis, for which surveys have been conducted for some 10 years. For von Willebrand disease (vWD) evaluations, a total of 47 plasma samples have been dispatched to survey participants, including representative samples from normal individuals plus all of the major vWD subtypes (i.e., types 1, 2A, 2B, 2M, 2N, and 3). These surveys have focused partly on the issue of diagnostic interpretive error rates associated with different assays and test panels. In this context, considerable improvement is seen when laboratories incorporate the vWF:collagen-binding assay into the test panel. Thrombophilia-associated tests assessed by the program and discussed in this review include activated protein c resistance, lupus anticoagulant, and deficiencies of protein C, protein S, and antithrombin. Other tests briefly reviewed here include factor assays and inhibitors, D-dimer, and heparin/anti-Xa assays. Anticardiolipin antibody and anti-beta(2)-glycoprotein I antibody (aB(2)GPI) testing, assessed by the Immunology QAP, is also reviewed briefly, as are genetic tests associated with thrombophilic markers such as factor V Leiden and the prothrombin gene.
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PMID:Emerging technologies and quality assurance in hemostasis: a review of findings from the Royal College of Pathologists of Australasia Quality Assurance Program. 1742 57

Thrombophilia-hypofibrinolysis may play an important role in rare premature (< or = age 45 years) arterial occlusive events in atherothrombotic cardiovascular (ATCVD) disease, particularly in normolipidemic patients. Whether thrombophilia-hypofibrinolysis contributed to ATCVD < or = age 45 years was assessed in 78 men and 40 women with 230 ATCVD events (myocardial infarction (MI) [n = 60], coronary artery bypass graft [CABG, n = 33], angioplasty [n = 52], chronic angina [n = 41], ischemic stroke [n = 11], transient ischemic attack [TIA, n = 24], claudication [n = 9]). Cases were compared with healthy normal adult controls (44 men and 76 women). In men, the Factor V Leiden mutation was present in 6/63 (10%) cases versus 0/44 (0%) controls (P = 0.042), Factor VIII was high (>150%) in 16/60 (27%) cases versus 1/42 (2%) controls (P = 0.001), Factor XI was high (>150%) in 9/57 (16%) cases versus 0/42 (0%) controls (P = 0.009), and plasminogen activator inhibitor activity (PAI-Fx) was high (>21.1 U/mL) in 15/63 (24%) cases versus 3/43 (7%) controls (P = 0.023). In women, protein C was low (<73%) in 4/26 (15%) cases versus 0/74 (0%) controls (P = 0.004), and free protein S was low (<66%) in 5/27 (19%) cases versus 2/74 (3%) controls (P = 0.014). In women, Factor XI was high (>150%) in 3/27 (11%) cases versus 1/74 (1%) controls (P = 0.057), and the lupus anticoagulant was present in 9/32 (28%) cases versus 2/51 (4%) controls (P = 0.002). In patients with ATCVD < or = age 45 years, thrombophilias (Factor V Leiden, Factor VIII, Factor XI, protein C and S deficiency, lupus anticoagulant) and hypofibrinolysis (PAI-Fx, Lp[a]) may promote arterial thrombosis, which is synergistic with atherosclerotic endothelial injury.
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PMID:Thrombophilia-hypofibrinolysis and atherothrombotic cardiovascular disease < or = age 45 years. 1765 28

Thrombophilia is considered to increase the risk of venous thrombosis (VT) due to hemostasis activation. To determine the level of hemostasis activation in thrombophilic subjects with or without a history of VT, hemostasis activation markers prothrombin fragment 1 and 2 (F1+2), thrombin-antithrombin complex (TAT), and cross-linked fibrin degradation products (D-dimer) were measured in 94 subjects with (patients) and 101 subjects without a history of VT (controls). A total of 34.8% of patients and 14.8% of controls (P= .002) had at least 1 thrombophilic defect (protein C deficiency, activated protein C [APC] resistance, presence of lupus anticoagulants, or prothrombin G20210A polymorphism). The subjects were divided into 4 subgroups: patients with (TF(+) patients) and without (TF(-) patients) thrombophilia, and controls with (TF(+) controls) and without (TF(-) controls) thrombophilia. Hemostasis activation was comparable between all patients and controls (TAT: 2.1 vs 2.6 microg/L; F1+2: 1.0 vs 0.9 nmol/L; D-dimer: 36 vs 37 microg/L, respectively) and between TF(+) and TF(- ) patients. However, TF(+) controls had a significantly higher prevalence of increased hemostasis activation markers compared with TF(-) controls (TAT>4.4 microg/L, 38.4 vs 7.3%; F1+2>1.1 nmol/L, 53.8 vs 22.0%; D-dimer >78 microg/L, 30.7 vs 8.8% of subjects, respectively; all P< .05). After stratification for thrombophilic defects, hemostasis activation was associated with APC resistance in controls and with protein C deficiency in patients. To conclude, thrombophilia was associated with hemostasis activation in controls. We assumed that, in patients, the differences in hemostasis activation between subjects with or without thrombophilia were blurred due to undetermined and unidentified thrombophilic defects.
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PMID:Hemostasis activation in thrombophilic subjects with or without a history of venous thrombosis. 1789 9


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