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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arterial thrombosis results from endovascular injury and, to a lesser extent, alterations in hemostatic equilibrium. Although multiple hereditary and acquired hemostatic risk factors have been described in the pathophysiology of venous thrombosis, the degree and type of abnormalities that contribute to arterial thrombosis are less well understood. Endothelial cell injury with the elaboration of proinflammatory mediators stimulates the process of arterial thrombosis. Although this is most often the result of endovascular injury attributable to atherosclerotic disease, other disease states can elicit a similar response as well. Similarly, once thrombosis has been initiated, variations in the activity of coagulation proteins and endogenous anticoagulants, as well as the kinetics of platelet aggregation, may alter the effectiveness of thrombus formation. Epidemiological studies have identified several acquired or inherited states that may result in endothelial damage or altered hemostatic equilibrium, thereby predisposing patients to arterial thrombosis. These include hyperhomocysteinemia, elevated C-reactive protein, antiphospholipid antibodies, elevated fibrinogen, Factor VII, plasminogen activator inhibitor-1 (PAI-1), hereditary thrombophilias, and platelet hyper-reactivity. This review explores our present understanding of these risk factors in the development of arterial thrombotic events. At present, the literature supports a role for hyperhomocysteinemia, elevated C-reactive protein, and elevated fibrinogen as risk factors for arterial thrombosis. Similarly, the literature suggests that lupus anticoagulants and, to a lesser extent, elevated titers of cardiolipin IgG antibodies predispose to arterial vascular events. In certain subsets of patients, including those with concomitant cardiac risk factors, <55 years of age, and women, hereditary thrombophilias such as carriership of the factor V Leiden and the prothrombin G20210A mutations may confer a higher risk of arterial thrombosis. However, the data on Factor VII, PAI-1, and platelet receptor polymorphisms are contradictory or lacking.
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PMID:Assessment of hemostatic risk factors in predicting arterial thrombotic events. 1642 55

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

Maternal thrombophilias increases the risk of an adverse pregnancy outcome. An extensive literature review highlights the role of inherited and acquired thrombophilic disorders in spontaneous abortion, both early and late, recurrent or isolate, in intrauterine growth retardation, in placenta abruption, in pre-eclampsia and in venous thromboembolism. We have particularly focused attention on the following factors: antithrombin III (ATIII), proteins C (PC) and S (PS) deficiencies, genetic mutations particularly factor V Leiden (FVL), prothrombin gene G20210A (PTM) and the thermolabile variant of the methylene tetrahydrofolate reductase C677T (MTHFR) gene, lupus anticoagulant (LAC) and anticardiolipin antibodies, VIIIc factor, hyperhomocysteinemia and acquired activated protein C resistance. Appropriate treatment can improve pregnancy outcome without teratogenic effects.
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PMID:Inherited and acquired thrombophilia: pregnancy outcome and treatment. 1679 17

Hyperhomocysteinemia (HHcy), lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are independent risk factors for thrombosis. Even though risks are cumulative, the clinical impact of the association is unknown. Preliminary data suggested that HHcy might be associated with transient LA and ACA, disappearing after lowering HHcy. We prospectively evaluated the association of HHcy and LA/ACA, the effect of lowering HHcy with folic acid in LA behavior, and the correlation of the initial dRVVT with LA behavior after folic acid in 210 patients with thrombosis and adverse pregnancy outcomes. Prevalence of HHcy among patients with LA/ACA was 40%. Thirty-one patients exhibited only HHcy (15%; Group 1), 106 (50%; Group 2) had only LA/ACA, while 73 (35%; Group 3) had both. After therapy, 63% and 64% of LA/ACA remained positive in Group 3 and 2, respectively. We observed a trend towards a more positive dRVVT in persistent LA after lowering HHcy. No differences in clinical presentation or in outcomes after two years of followup were observed among the groups. Even though the association of HHcy and LA/ACA is common in patients with thrombosis, it might have no prognostic implications if Hcy levels are lowered. Currently, no laboratory findings correlate with LA behavior, which is independent of homocysteine levels and vitamin treatment.
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PMID:Antiphospholipid antibodies and hyperhomocysteinaemia in patients with vascular occlusive disease. 1680 46

Homocysteine (Hcy), a sulfur-containing amino acid, is eliminated through B vitamins-dependent pathways. Hyperhomocysteinemia has been found to be an independent risk factor for atherosclerotic cardiovascular, cerebrovascular, and peripheral vascular diseases. Recently, psoriasis, lupus, and rheumatoid arthritis were reported to be associated with hyperhomocysteinemia. This study was aimed to evaluate the changes of plasma Hcy level before and after sulfasalazine and MTX therapy in patients with ankylosing spondylitis (AS). One hundred and two patients with AS and ten normal controls were enrolled in the cross-sectional case-control study. Fasting plasma Hcy levels were determined by ELISA kits (IMX, Abbott). Hcy levels were compared to their Bath AS disease activity index (BASDAI) and the usage of sulfasalazine and/or MTX. Active disease was defined by BASDAI as more than 3 in a 10-cm scale with ESR >20 mm/h. For those patients with plasma Hcy >or=15 micromol/l, a perspective trial of daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg for 2 weeks were also tested for the efficacy. Plasma Hcy level increased significantly in AS patients under sulfasalazine (10.4+/-3.8 micromol/l, p<0.05), MTX (11.9+/-4.7, p<0.05) and sulfasalazine/MTX combination treatment (11.2+/-2.6, p<0.05) compared with normal controls (8.6+/-1.2 micromol/l) and AS patients without DMARD(9.4+/- 2.6 micromol/l). No correlation between disease activity and plasma Hcy level was found. Daily supplement of vitamin B-12 0.5 mg, B-6 50 mg, and folic acid 5 mg can lower Hcy level in 2 weeks (32.3+/-24.0 vs 15.6+/-11.1 micromol/l, p=0.007). Plasma homocysteine level did significantly increase in AS patients under sulfasalazine or MTX treatment. B-vitamins should be considered as a routine supplementation for patients who underwent sulfasalazine and/or MTX treatment. Further longitudinal studies are required to confirm the conclusions.
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PMID:Plasma homocysteine status in patients with ankylosing spondylitis. 1702 18

Abnormal increases of antiphospholipid antibody and plasma homocysteine levels are recently emerging as nonlipidic risk factors for cerebral atherogenesis and thrombosis. Both antiphospholipid antibody and homocysteine share many similar bioeffects in hemostasis, but their interaction is still inconsistent. In this study, we examined the relation between the plasma homocysteine level and lupus anticoagulant, anticardiolipin antibody, and anti-beta2-glycoprotein I antibody in patients with noncardiac cerebral ischemia. Systemic lupus erythrematosus patients were excluded. The results showed a higher frequency of moderate hyperhomocysteinemia in patients with an abnormal increase of lupus anticoagulant only. Neither the serum folate and cobalamin levels nor methylenetetrahydrofolate reductase allele mutation contributes to this result. Accordingly, homocysteine interacts with lupus anticoagulant to promote cerebral atherosclerosis and ischemia. The role of vasculopathic or prothrombotic autoantibody generation in response to specific pathological change such as hyperhomocysteinemia warrants further investigation.
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PMID:Hyperhomocysteinemia relates to the subtype of antiphospholipid antibodies in non-SLE patients. 1791 Nov 91

Epidemiological studies conducted over the past 25 years have provided ample support for the association of mild hyperhomocysteinemia (HHcy) with an elevated risk of atherothrombosis. Since autoimmune disorders (AD) are frequently associated with relevant and early signs of atherothrombotic damage not adequately explained by the traditional risk factors involved in the onset of cardiovascular disease (CVD), a large interest has been shown to the putative role of mild HHcy in this setting. On the basis of such considerations, we focused the attention on the relationship between homocysteine (Hcy) and CVD in patients affected with autoimmune diseases, reviewing the most recent literature data and also providing our original experience. Although the large amount of available studies clearly shows that HHcy represents a common finding in patients affected with several autoimmune diseases, the actual role of Hcy in the development of CVD in the course of AD is not clear yet, perhaps, with the only exception of the systemic lupus erythematosus. In the other conditions, the role of Hcy in the pathogenesis of vascular complications is still a matter of debate, as the result of conflicting reports and/or lack of an adequate body of investigation.
Lupus 2007
PMID:Hyperhomocysteinemia: a cardiovascular risk factor in autoimmune diseases? 1797 57

The risk factors for deep venous thrombosis (and for cerebral vein and sinus thrombosis, CVST) differ from those for arterial disease. The risk factors for venous thrombosis are linked to the Virchow triad of stasis of the blood, changes in the vessel wall, and changes in the composition of the blood, especially the first and third of these. Risk factors are usually divided into acquired (e.g. surgery, trauma, pregnancy, puerperium, lupus anticoagulant, malignant disease, and female hormones) and genetic (congenital thrombophilia). However, the separation of genetic and acquired risk factors is somewhat artificial, since they have additive effects and venous thrombosis is often multifactorial. In this review, we discuss acquired risk factors for CVST. These include hormonal changes (e.g. oral contraceptives use, hormone replacement therapy, pregnancy and puerperium), mechanical precipitants (e.g. head trauma, jugular catheterization, surgery, lumbar puncture), local and generalized infections, cancer, acquired prothrombotic states (e.g. hyperhomocysteinemia, nephrotic syndrome), inflammatory diseases (e.g. vaculitis, intestinal inflammatory disease), hematological disorders, neurological diseases (e.g. dural arteriovenous malformations, spontaneous intracranial hypotension), drugs and other situations. However, only some conditions are consistently present in case series, while many appear only in anecdotal reports. Thus, in most situations, a causal link cannot be established. Determining a cause-and-effect relationship is essential for developing preventive, diagnostic, and therapeutic strategies. Therefore, further multicentered, case-controlled studies are crucial for better understanding the pathogenesis of CVST.
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PMID:Risk factors of cerebral vein and sinus thrombosis. 1800 52

During the last decade, the role of inflammation in the etiopathogenesis of arterial thrombosis has been elucidated. However, little is known about the relationship between inflammation and venous thrombosis. Recently, inflammation has been accepted as a possible mechanism through which different risk factors trigger thrombus formation in veins. The data indicate that inflammation of the vessel wall initiates thrombus formation in an intact vein and that inflammation and coagulation systems are coupled by a common activation pathway. The first event in thrombus formation is most probably activation of endothelial cells, platelets and leucocytes, with initiation of inflammation and formation of microparticles that trigger the coagulation system through the induction of a tissue factor. Therefore, the key event in the initiation of venous thrombus formation is most probably vein wall inflammation. However, expected relationship between inflammatory markers as indicators of inflammatory process and clinical venous thromboembolism (VTE) has not yet been elucidated. C-reactive protein does not appear to be useful in predicting future venous thrombosis or to be useful in the diagnosis of VTE. Recently, it was demonstrated that probable association between VTE and several other markers of inflammation such as: interleukin (IL)-6, IL-8 and tumor necrosis factor-a exists. While these markers of inflammation were studied during or after acute venous thrombosis, further prospective studies are needed to determine the predictive value of inflammatory markers for VTE. The identification and elucidation of inflammatory markers relevant to venous thrombosis could provide targets for future therapy. That inflammation is the basic etiopathogenetic process of VTE is also supported by the relation of some risk factors to both arterial and venous thrombosis: age, increased body mass index, hypercholesterolemia, hypertension, lupus anticoagulant and hyperhomocysteinemia. A relation was also found between preclinical and clinical atherosclerotic disease and VTE. Also in line with these arguments are the preventive effects of aspirin and statins in both arterial and venous disease.
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PMID:The role of inflammation in venous thromboembolism and the link between arterial and venous thrombosis. 1809 97

The objective of this study was to compare oxidative status and homocysteinemia in patients with lupus nephritis (LN) and in controls. Total antioxidant capacity (TAC), reactive oxygen species (ROS), homocysteine and related vitamins were measured in 68 patients with LN and in 50 controls. LN patients had lower TAC (p = 0.05) and higher ROS and homocysteinemia (p = 0.01) than controls. TAC, significantly lower in active than in quiescent LN (p = 0.01), was correlated with albuminemia (p = 0.02), inversely with proteinuria (p = 0.01) and anti-DNA antibodies (p = 0.004). ROS values, higher both in active and in inactive LN, correlated with age (p = 0.02), C-reactive protein (CRP) (p = 0.0005) and inversely with prednisone dosage (p = 0.05). At multivariate analysis, CRP (p = 0.04) and age (p = 0.005) were independent ROS predictors. Homocysteine, higher in active than in quiescent LN (p = 0.016) and in patients with antiphospholipid antibodies (p=0.05), correlated with serum creatinine (p = 0.00001) and proteinuria (p = 0.015). At multivariate analysis serum creatinine (p = 0.006) and active nephritis (p = 0.003) were independent predictors of hyperhomocysteinemia. Patients with LN showed impaired oxidative status, even without clinical signs of renal activity. ROS production may be counterbalanced by adequate antioxidant capacity in some patients with quiescent LN. The association of hyperhomocysteinemia and antiphospholipid antibodies positivity may increase the risk of cardiovascular and/or thrombotic events in LN patients.
Lupus 2010 Jan
PMID:Oxidative stress and homocysteine metabolism in patients with lupus nephritis. 1993 21


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