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)

Lupus anticoagulants (LAs) are immunoglobulins which prolong 1 or more of the in vitro phospholipid-dependent tests of coagulation (e.g., activated partial thromboplastin time [APTT], dilute Russell viper venom time [dRVVT], kaolin clotting time [KCT], and textarin time [TT]). Paradoxically, patients with LAs rarely experience hemorrhagic problems. Approximately 1/3 of individuals with LAs experience thromboembolic complications such as stroke, deep vein thrombosis, and pulmonary emboli. LAs are members of the antiphospholipid antibody (APA) family. The APA family includes: LAs, anticardiolipin antibodies (ACAs), and reagin (the antibody responsible for the positive serologic test for syphilis). In approximately 60% of the patients, a LA and an ACA will both be present. The diagnosis of LAs requires an organized approach. Careful preparation of platelet poor plasma (PPP) is essential to assure maximum detection of LA. In order to rule out LAs, it is necessary to perform at least 2 screening tests (e.g., APTT, dRVVT). Additional steps in the diagnosis of LAs include mixing studies to identify the presence of an inhibitor and confirmatory procedures to demonstrate phospholipid-dependence of the inhibitor. It is also important to rule out any other potential coagulopathies which may account for the prolonged screening studies.
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PMID:Lupus anticoagulants: diagnostic dilemma and clinical challenge. 1016 22

Antiphospholipid antibodies syndrome has emerged as an important entity responsible for stroke in young. Seven cases of young stroke (< 40 years of age) with mean age of 30.1 years (age range 25-39 years, 2 males and 5 females), who tested positive for antiphospholipid antibodies are being reported. All subjects had completed strokes. Six had arterial ischaemic and one patient had venous stroke. One patient suffered from four episodes, three ischaemic and one intracerebral haemorrhage. Two patients suffered from foetal loss. Generalised tonic clonic seizures occurred in three patients. Deep vein thrombosis was observed in one case. Thrombocytopenia was not observed in any case. All the patients had elevated anticardiolipin antibodies (aCL) IgM or IgG, while Lupus anticoagulant (LA) was elevated in 4 cases. Six cases belonged to primary antiphospholipid antibodies syndrome and one to lupus like illness. Oral anticoagulants were administered to maintain a high intensity international normalized ratio (INR). No recurrences were observed during a follow up period of 6-18 months.
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PMID:Antiphospholipid antibodies syndrome in 'Stroke in young'. 1040 37

The role of hereditary antithrombotic protein defects in juvenile deep vein thrombosis (DVT) was evaluated. Fifty six young patients (age <45 yr) with doppler-proven DVT were investigated for the presence of resistance to activated protein C (APC-R), lupus anticoagulant (LA), anticardiolipin antibodies and deficiencies of protein C, protein S, ATIII activities. Fifty nine normal healthy individuals served as controls. APC-R was observed to be the commonest defect underlying the Indian DVT as seen in 39.2% of patients followed by elevated ACA (5.3%), PAI (2.8%), presence of LA (2.8%) and reduced ATIII levels (2.8%). None of the subjects had protein C or S deficiency. APC-R was associated with ATIII deficiency in one case, and elevated ACA in two cases. In two subjects, APC-R was associated with elevated PAI levels. Patients with more than one prothrombotic factor had a higher prevalence of pulmonary thromboembolism, suggesting that the thrombogenic potential of APC-R is enhanced by the presence of coexisting hereditary or acquired prothrombotic defect.
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PMID:Pathogenetic factors underlying juvenile deep vein thrombosis (DVT) in Indians. 1041 51

Antiphospholipid antibodies [such as anticardiolipin antibodies (ACLA)] are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. The most common thrombotic events associated with ACLA are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome) or cerebrovascular/retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). Type V patients are those with antiphospholipid antibodies and fetal wastage syndrome. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of ACLA in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through VI) should be defined, if possible, as this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with ACLA, patients with primary lupus anticoagulant thrombosis syndrome usually suffer venous thrombosis. Because the activated partial thromboplastin time (aPTT) is unreliable in patients with lupus anticoagulant (prolonged in only about 40 to 50% of patients) and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests including ELISA for ACLA, the dRVVT for lupus anticoagulant, hexagonal phospholipid neutralization procedure, and B-2-GP-I (IgG, IgA, and IgM) should be immediately ordered when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If these are negative, in the appropriate clinical setting, subgroups should also be assessed. Finally, most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy and, except for retinal vascular thrombosis, most will fail antiplatelet therapy, thus it is of major importance to make this diagnosis in order that patients can be treated with the most effective therapy for secondary prevention, low-molecular weight heparin (LMWH) or unfractionated heparin (UHF) in most instances.
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PMID:Antiphospholipid syndrome and thrombosis. 1044 63

We systematically screened for the aetiology of thrombophilia in 115 patients with venous, arterial and small vessel thromboses. Forty-one patients (36% of those we examined) suffering from a variety of thromboses, including deep vein thrombosis, pulmonary embolism, arterial occlusion, cerebral infarction, Moyamoya disease and ulcerative colitis, were characterized either with positive lupus anticoagulants or with decreased activities of protein S, protein C, antithrombin III and/or plasminogen. Eight mutation sites were confirmed in 11 thrombotic patients using gene analysis. Decreased protein S activity was found with a high incidence (23 out of 115) in Japanese patients who suffered from not only venous thrombosis but also arterial and small vessel thrombosis. We emphasize here the important role of protein S in the pathogenesis of thrombosis in the Japanese population.
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PMID:Screening for aetiology of thrombophilia: a high prevalence of protein S abnormality. 1045 3

Reported are two patients presenting with both thrombocytopenia and sagittal sinus thrombosis. The first patient is a 42-month-old male with no identified thrombophilic risk factors who developed acute neurologic symptoms after an acute infection. The second patient is a 22-month-old female with no history of preceding infection but had a positive lupus anticoagulant test. She also developed deep venous thrombosis and was treated with intravenous heparin. Both patients are currently doing well without neurologic deficits. To the authors' knowledge the second patient is the youngest reported patient with cerebral vein thrombosis associated with thrombocytopenia and lupus anticoagulant. These observations call attention to the need for a thorough investigation of thrombophilic risk factors in pediatric patients with thrombotic complications.
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PMID:Sagittal sinus thrombosis associated with thrombocytopenia: a report of two patients. 1046 47

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 patient with newly diagnosed multiple myeloma manifested by urine kappa light-chain excretion and a small monoclonal spike (0.4 g/dl), presented with lower extremity deep venous thrombosis. A preheparin plasma-activated partial thromboplastin time (aPTT) was prolonged at 68 sec (normal control 26-42 sec). Additional studies confirmed the presence of lupus anticoagulant activity in the serum: the modified Russell Viper Venom Time (MRVVT) was 73 sec (normal control 24-42 sec) and with a 50:50 mix of the patient's plasma and pooled normal plasma, the MRVVT remained prolonged. Kappa light chains (LC) were isolated from the patient's urine and their purity confirmed by electrophoresis and immunofixation using specific immunoglobulin antisera. The patient's LC mixed with pooled normal plasma demonstrated LA activity by in vitro clotting tests (plasma-activated partial thromboplastin time 62 sec, with normal control of 45 sec), MRVVT of 44 sec with normal control of 35 sec. Purified urinary kappa light chains from a control patient with multiple myeloma and normal clotting studies, failed to prolong either the plasma-activated partial thromboplastin time or the MRVVT. We hypothesize that kappa LC in our patient demonstrated LA activity, which was unique to these LCs. Paraproteins with LA activity, to date, have included only intact immunoglobulins (Ig). While intact Ig paraproteins have been reported to possess LA activity, this is the first report to our knowledge of light-chain paraproteins possessing similar activity and resulting in clinically evident thrombosis. Light chain paraproteins could serve as useful models for further study of the mechanisms of activity of acquired LA inhibitors.
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PMID:Light-chain paraproteins with lupus anticoagulant activity. 1050 4

To establish the prevalence of antibodies against beta2-glycoprotein I (beta2GPI) in unselected patients with venous thromboembolism, as well as the association with antiphospholipid antibodies (aPL) and a history of previous thromboembolism, we investigated the presence of these antibodies in 227 consecutive patients with acute deep vein thrombosis or pulmonary embolism, of whom 63 were carriers of aPL with or without lupus anticoagulant (LA), and seven were carriers of LA alone. The presence of antibodies against beta2GPI was demonstrated in 19 patients [8.4%; 95% confidence interval (CI), 4.5-11.3%]. All of them belonged to the group of 63 patients with aPL (30.2%). A history of a previous thromboembolism was identified in 11 of the 19 patients with anti-beta2GPI antibodies (57.9%) and in 45 of the 208 patients without these antibodies [21.6%; odds ratio (OR)=4.98; 95% CI, 1.89-13.1; p<0.0005]. In the subgroup of patients with aPL and/or LA, the rate of recurrent thromboembolism among patients with anti-beta2GPI antibodies (11 of 19, 57.9%) was significantly higher than that observed in patients without these antibodies (15 of 51, 29.4%; OR=3.3; 95% CI, 1.1-9.83; p=0.28). We conclude that in patients with acute venous thromboembolism the prevalence of antibodies against beta2GPI is unexpectedly high. The presence of these antibodies seems to identify a subgroup of patients with antiphospholipid antibodies who have a peculiarly high risk of thrombotic recurrences. Further prospective studies are indicated to better define the role of anti-beta2GPI antibodies in the development of recurrent thromboembolism.
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PMID:Anti-beta2-glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism. 1059 29

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


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