Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alanine/valine (A/V) gene polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes catalyzing remethylation of homocysteine, has been reported and the VV genotype is associated with increased plasma homocysteine levels as a result of the reduced activity and increased thermolability of this enzyme. Although previous studies have suggested that the VV genotype is a risk factor for arterial occlusive disease, whether the VV genotype is a risk factor for venous thrombosis is still controversial. Here we screened 72 Japanese patients with deep venous thrombosis (DVT) and 85 controls for this mutation, and we measured plasma levels of homocysteine to determine whether the thermolabile variant with the VV genotype is a risk factor for DVT in a Japanese population. Of the 72 patients with DVT, 10 (13.9%) were found to be homozygous for the VV genotype, and in 6 (7.0%) of 85, control individuals and the difference was not significant (odds ratio=2.12, 95% CI=0.73-6.16, p=0.19). When we divided the DVT patients into subgroups, with and without predisposition of thrombophilia, including deficiencies of proteins C and S, plasminogen, and lupus anticoagulant, the prevalence of the VV genotype in DVT patients with predisposition was significantly higher than that of the normal controls (odds ratio=5.99, 95% CI=1. 56-22.96, p=0.01). However, the prevalence of the VV genotype in DVT patients without predisposition was not significantly different from that of the normal controls (odds ratio=1.20, 95% CI=0.32-4.47, p=0. 75). The plasma homocysteine levels in patients with DVT (11.6+/-5.2 nmol/ml) was not significantly different from that of the control subjects (11.6+/-3.7 nmol/ml). Individuals with the VV genotype showed higher plasma homocysteine levels (15.4+/-6.9 nmol/ml) than did individuals with the AV genotype (11.2+/-3.7 nmol/ml, p=0.009) or in individuals with the AA genotype (11.1+/-4.2 nmol/ml, p=0.004). Serum folate and vitamin B12 levels were not correlated with the plasma homocysteine levels. In conclusion, even though homozygosity for the VV genotype of the MTHFR gene was associated with higher plasma homocysteine levels, we found no association between plasma levels of homocysteine and DVT or between the genotype of the MTHFR gene and the DVT incidence. However, we found that the VV genotype of the MTHFR gene is a risk factor for DVT only when combined with the predisposition of thrombophilia.
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PMID:Common C677T polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predisposition of thrombophilia. 1070 28

Antibodies to prothrombin have been associated with venous and arterial thrombosis, and they cross-react with a structurally closely related protein plasminogen. We immunised 16 mice with human prothrombin and 15 mice with human plasminogen. Mice immunised with prothrombin developed cross-reactive antibodies to plasminogen (12/16), beta2-glycoprotein I (4/16), tissue-type plasminogen activator (6/16) and cardiolipin (11/16). Mice immunised with plasminogen developed cross-reactive antibodies to prothrombin (8/15), tissue-type plasminogen activator (2/12) and cardiolipin (5/12). Functional effects of antibodies were examined. Immunisation with prothrombin induced lupus anticoagulant activity in 9/14 mice. In mice immunised with plasminogen, radial fibrinolysis was inhibited in 8/10 and plasminogen activation in the chromogenic assay was inhibited in 9/11. No cross-functionality was observed. In conclusion, antibodies to prothrombin and plasminogen cross-react in vivo. Antibodies to prothrombin and plasminogen have different functional profiles, immunisation with prothrombin leads to prolonged blood clotting time, and immunisation with plasminogen induces antibodies interfering with fibrinolysis.
Lupus 2001
PMID:Immunologic and hematologic properties of antibodies to prothrombin and plasminogen in a mouse model. 1123 22

We have attempted to establish a systematic pathogenetic analysis of thrombophilia by including assays of antithrombin III(AT III), protein C(PC), protein S(PS), fibrinogen, plasminogen and heparin cofactor II by both functional and immunological methods as well as detecting lupus anticoagulants. Such a comprehensive scheme was instrumental in systematically identifying and confirming the pathogenesis of 164 cases which otherwise would have escaped detection since 1994 in our laboratory (Kyushu University Hospital). The analysis was conducted on 485 consecutive patients with venous thrombosis, arterial thrombosis and disorders in which small vessel thrombosis were implicated. Hundred and sixty four patients, (40% of the examined patients), were found to have low activities of PS, PC, ATIII etc. Among them, seventy five patients(46%) had low PS activity, and twenty nine(18%) had low PC activity. Genetic analyses performed on specimens with low PS/PC activities resulted in the confirmation of 24 genetic abnormalities. Such genetic abnormalities, however, does not solely lead to the pathogenesis of thromboses. We have found that some genetic polymorphisms, such as PS Tokushima, factor XII 46C allele, were also additional risk factors for thromboses.
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PMID:[Genetic polymorphism and risk of thromboses]. 1130 10

The etiologic role of thrombotic and fibrinolytic disorders in Perthes' disease has not been determined. A case control study was conducted to determine whether thrombotic and fibrinolytic disorders are associated with Perthes' disease. Twenty-six patients with Perthes' disease were matched with 26 control patients for gender, age (2-year range), and time of presentation (1-year range). Thrombotic disorders were investigated for protein C activity, protein S activity, antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus anticoagulant. Fibrinolytic disorders were investigated for tissue-plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-1 to tissue plasminogen activator ratio, lipoprotein (a), and plasminogen. The activity of protein C, which suppresses factor Va and leads to an increase of coagulant activity when decreased, was increased in patients. There were no significant differences in the levels of other factors between the patients and controls. No evidence was found to prove a relationship between Perthes' disease and thrombotic or fibrinolytic disorders in the patients in the current study.
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PMID:Role of thrombotic and fibrinolytic disorders in the etiology of Perthes' disease. 1201 5

Anti-prothrombin antibodies are a frequent cause of lupus anticoagulant (LAC), a thrombotic risk factor. Prothrombin shares structural homology with plasminogen, a kringle protein with an important role in fibrinolysis. Cross-reactivity between antiprothrombin antibodies and plasminogen has been described. To study associations between LAC, IgG and IgM class antiprothrombin and antiplasminogen antibodies, plasminogen activity levels and thrombosis in selected patients with systemic autoimmune diseases. Patients included forty-six consecutive LAC-positive patients (29 with systemic lupus erythematosus (SLE); 33 with a thrombotic history), 38 patients without LAC (36 with SLE; seven with a history of thrombosis) and 40 healthy controls. In the total group of 84 patient samples, the prevalence of antiprothrombin and antiplasminogen antibodies was 30 and 38%, respectively. There was no significant relationship between the presence of these antibodies. In contrast to presence of antiplasminogen antibodies, presence of antiprothrombin antibodies was statistically significant related to thrombosis. Thirteen samples had antiprothrombin and antiplasminogen antibodies of similar isotype (IgG, n= 4; IgM, n= 9). Of these, all but one had LAC and 11/13 came from patients with a history of thrombosis. Simultaneous presence of IgM-class antiprothrombin and antiplasminogen antibodies had a significant association with thrombosis. Levels of plasminogen activity were similar in samples from healthy controls and patients (with or without antiplasminogen antibodies or thrombosis). Anti-prothrombin antibodies and antiplasminogen antibodies occur frequently in patients with systemic autoimmune disease. Anti-prothrombin antibodies, but not antiplasminogen antibodies are a risk factor for thrombosis. Anti-plasminogen are in most cases unrelated to antiprothrombin antibodies.
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PMID:A study on associations between antiprothrombin antibodies, antiplasminogen antibodies and thrombosis. 1287 9

The influence of anticoagulation components of hemostasis system and lupus anticoagulants (LA) upon the course of multiple sclerosis (MS) was studied. 57 patients with MS diagnosed according to McDonald's criteria (McDonald WI et al., 2001) were examined: 19 males and 38 females aged 16-62 (mean age 36.8 +/- 11.2 yrs) with 1-25 yrs history of MS (mean duration 8.1 +/- 5.7 yrs). 42 patients suffered from relapsing-remitting MS, 17 patients were affected by secondary progressive MS. The degree of neurological deficit was estimated in remission according to Expanded Disability Status Scale (EDSS), mean score was 3.8 +/- 1.7. The progression of MS was estimated as EDSS score per year ratio. In patients with relapsing-remitting MS the mean number of exacerbations per year was calculated. The following laboratory findings were evaluated: thrombin clotting time, antithrombin-III activity, plasminogen reserve by the level of streptokinase-induced euglobulin fibrinolysis, protein C activity, factor Va resistance to activated protein C, lupus anticoagulants (LA). It was revealed that LA could worsen relapsing-remitting MS: in LA-positive patients there were 1.41 +/- 0.69 exacerbations per year and progression score reached 0.82 +/- 0.30, whereas in LA-negative patients the figures were 0.74 +/- 0.58 (p < 0.001) and 0.48 +/- 0.33 (p < 0.01) respectively. All the patients showed decrease of protein C activity (p < 0.001) with no relation to LA activity or factor Va resistance to activated protein C. Normal level of plasminogen and antithrombin-III activity was supposed to be the marker of benign variant of MS. The course of MS was mild in patients with high antithrombin-III activity even if they were hypercoagulative--this suggests neuroprotective activity of antithrombin-III which may relate not only to its anticoagulation effect.
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PMID:[The role of hemostasis system in the pathogenesis and course of multiple sclerosis]. 1293 32

Some studies have suggested that thrombotic and fibrinolytic disorders may be etiologic causes of osteonecrosis of the femoral head. A case-control study was done to determine whether these disorders are associated with osteonecrosis of the femoral head in East Asian patients with nontraumatic osteonecrosis of the femoral head. Twenty-four consecutive patients who had been diagnosed as having nontraumatic osteonecrosis of the femoral head were matched with 24 control subjects for gender, age (1-year range), and the time of presentation (1-year range). Thrombotic factors including protein C activity, protein S activity, antithrombin III, anticardiolipin antibody immunoglobulins G and M, and lupus antibody were investigated. Fibrinolytic factors including tissue-plasminogen activator, plasminogen activator inhibitor-1, tissue-plasminogen activator and plasminogen activator inhibitor-1 ratio, lipoprotein (a), and plasminogen also were investigated. There were no significant differences in the levels of thrombotic and fibrinolytic factors. In eight patients with idiopathic osteonecrosis, anticardiolipin antibody immunoglobulin G, an antiphospholipid antibody which is associated with thrombotic phenomena, was lower than that in respective control subjects. These data do not confirm an etiologic role for thrombotic and fibrinolytic disorders in East Asian patients with nontraumatic osteonecrosis of the femoral head.
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PMID:Role of thrombotic and fibrinolytic disorders in osteonecrosis of the femoral head. 1464 26

Coagulopathy is a life-threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell-free dialysis technique, on the blood coagulation of cirrhotic patients. From February 2002 to July 2002, nine patients--five males (55.5%) and four females (44.4%), age 47-70 yr (median 56)--underwent 12 courses (4-7 sessions each) of MARS. Patients were treated for the following indications: six (66.6%) acute-on-chronic hepatic failure, three (33.3%) intractable pruritus. Platelet count, prothrombin time (PT), international standardized ratio and thromboelastography were measured before and after each MARS session. Coagulation factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand, lupus anticoagulant, protein C, protein S, antithrombin III, plasminogen, alpha 2 antiplasmin, D-dimer, fibrin monomers, complement, and C(1) inactivator were measured before and at the end of each MARS treatment. We found a statistically significant difference (p < 0.05) in the platelet count, PT, all the thromboelastograph variables (reaction and constant time, alpha angle, and maximal amplitude), factor VIII, von Willebrand, and D-dimer, when measured before and after MARS. Previous reports have shown amelioration of blood coagulation following MARS treatments. However, we document that MARS induces coagulopathy through a platelet-mediated mechanism, whereby platelet may be mechanically destroyed during the passage of blood through the filters and lines. An alternative postulated mechanism is an immune-mediated platelet disruption - coagulopathy.
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PMID:Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system. 1523 11

Patients with end-stage renal disease are prone to hemorrhagic complications and simultaneously are at risk for a variety of thrombotic complications such as thrombosis of dialysis blood access, the subclavian vein, coronary arteries, cerebral vessel, and retinal veins, as well as priapism. The study was devised for the following purposes: (1) to identify the markers of thrombophilia in hemodialyzed patients, (2) to establish a role for antiphospholipid antibodies in thrombosis of the vascular access, (3) to characterize phospholipid antibodies in hemodialysis patients, and (4) to study the effects of dialysis on coagulation cascade. A group of 20 hemodialysis patients with no thrombotic complications (NTC) and 20 hemodialysis patients with thrombotic complications (TC) were studied along with 400 volunteer blood donors. Patients with systemic lupus erythematosus and those with nephrotic syndrome were excluded. All patients underwent a screening prothrombin time, activated partial thromboplastin time, fibrinogen (Fg), coagulation factors of the intrinsic and extrinsic pathways, antithrombin III (AT-III), protein C (PC), protein S (PS), resistance to activated protein C, prothrombin activation fragment 1+2 (F1+2), plasminogen, tissue type plasminogen activator (t-PA), plasminogen tissue activator inhibitor type-1 (PAI-1), anticardiolipin antibodies type M and G (ACA-IgM and ACA-IgG), lupus anticoagulant antibodies, and antiprothrombin antibodies type M and G (aPT-IgM and aPT-IgG). The study showed that PAI-1, F 1+2, factor VIII, ACA-IgM, and aPT-IgM levels were increased significantly over controls both in TC and NTC, however, they could distinguish patients with thrombotic complications from those without, being increased maximally in the former group. The novelty of the study is represented by the significant aPT increase that was observed in non-systemic lupus erythematosus hemodialysis patients, and particularly in those with thrombotic events. In addition, there was a reduction of factor XII during the treatment. It is possible to assume in the TC group and, to a lesser extent, also in the NTC group that endothelial cells liberate PAI-1 in the vascular lumen, which causes hypofibrinolysis. In addition, an excess of factor VIII is activated by endothelial dysfunction with subsequent activation of the coagulation cascade as shown by increased F1+2 and fibrinogen. ACA-IgM, in turn, is capable of interfering with the system of protein C, a potent anticoagulant factor that inactivates cofactors Va and VIIIa. They also induce the expression of procoagulant factors on the surface of the endothelial cells. In conclusion, the hypercoagulable state caused by alterations of coagulation and fibrinolytic factors is a cause of vascular access dysfunction and thrombosis of other vessels.
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PMID:Plasma levels of plasminogen activator inhibitor type 1, factor VIII, prothrombin activation fragment 1+2, anticardiolipin, and antiprothrombin antibodies are risk factors for thrombosis in hemodialysis patients. 1549 Apr 19

To study the etiological factors and pathogenisis of venous thrombi and their relations with anticoagulation and fibrinolysis, In 47 patients with venous thrombi anticardiolipin antibody (ACA) was detected by ELISA. lupus anticoagulant (LA) and anti-activative protein C resistance (APCR) were examined by coagulation test; factor V Leiden was determined by PCR; activity of anticoagulation and fibrinolysis of antithrombin (AT), protein C (PC), plasminogen (Plg) were detected by chromophore substrate methods. The results showed that ACA and/or LA were positive in 34% of patients with VT, most of which consisted of ACA IgG and LA; Plg was negative in 9.5% of patients; tPAI elevated in 8.3% of patients (much more than control group, P < 0.005); ATIII, PC, tPA were negative in 4.5%, 4.5%, 2.8% of patients, respectively (no significant difference with control groups, P > 0.05); ATIII, PC and Plg were negative constantly in one patient; factor V Leiden was not detected by PCR. There were no significant differences in anticoagulation and fibrinolysis between antiphospholipoprotein antibody (APA) negative subjects and APA positive subjects, 4 patients of which were positive in APCR, 3 patients were positive in ACA and/or LA, two out of three patients didn't achieved APCR reversion after mixing their blood plasma with normal blood plasma. It is concluded that antiphospholipoprotein antibody and abnormal fibrinolysis were the common pathological factors in venous thrombi. LA and/or ACA disturbs the anticoagulation aspect to develop into acquired APCR which may be a possible cause leading to thrombophilia.
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PMID:[Relationship of antiphospholipoprotein antibodies of venous thrombi with anticoagulation and fibrinolysis]. 1563 50


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