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 effect of beta 2glycoprotein I (beta 2GPI) and human monoclonal anticardiolipin antibody (aCL) on the protein S/C4b-binding protein (C4BP) system was evaluated. The binding of C4BP to protein S was assessed by ELISA in the presence of beta 2GPI with/without human monoclonal aCL. beta 2GPI downregulated the binding between S and C4BP significantly. Human monoclonal aCL abolished the beta 2GPI inhibitory effect in a calcium (Ca++) independent fashion. In separate experiments, the reactivity of aCL towards protein S in the presence or absence of beta 2GPI and cardiolipin was investigated. Monoclonal aCL bound to protein S only in the presence of a combination of beta 2GPI and cardiolipin. This binding was Ca++ dependent. These findings suggest that human monoclonal aCL increases the affinity of C4BP for protein S, and that protein S may represent one of the targets for aCL when combined with beta 2GPI and cardiolipin. Both issues may explain acquired free protein S deficiency and the attendant risk of thrombosis in patients with aCL.
Lupus 1997
PMID:Effect of beta 2glycoprotein I and human monoclonal anticardiolipin antibody on the protein S/C4b-binding protein system. 917 18

The antiphospholipid syndrome is defined as the association between the presence of antiphospholipid antibodies, detected as anticardiolipin antibodies and/or lupus anticoagulant, and a history of either arterial or venous thrombosis and/or recurrent pregnancy loss. Because thrombosis may occur in virtually any organ system, diagnosing the antiphospholipid syndrome and taking appropriate anticoagulation measures are important considerations in all medical specialties. Antiphospholipid antibody-associated thrombosis tends to recur. Antithrombotic prophylaxis to prevent recurrences is therefore needed. Prophylaxis in individuals with circulating antiphospholipid antibodies who have no history of thrombosis is still controversial. Although direct evidence for a pathogenetic role of antiphospholipid antibodies in the development of thrombosis is still lacking, recent studies suggest that it is causative rather than coincidental. New insights on the possible mechanisms leading to thrombosis were provided by the discovery of the serum cofactor (beta2-GPI), a coagulation inhibitor which is required for binding of anticardiolipin antibodies to cardiolipin. More recently, patients with antiphospholipid antibodies were found to possess autoantibodies directed against other coagulation factors, including prothrombin, protein C and protein S. Future studies should clarify whether these different antigenic specificities are associated with particular clinical events and assess the risk of thrombosis associated with the presence of antiphospholipid antibodies in asymptomatic individuals.
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PMID:The clinical significance of antiphospholipid antibodies. 918 33

We examined thrombophilic mechanisms and outcome in 54 patients with deep-vein thrombosis (DVT), who were otherwise apparently healthy and aged < or = 50 years. Patients were followed up 6 years (median) after a confirmed first DVT between 1987-1992 with no known predisposing illnesses. Patients were traced through the hospital registry and compared with 25 matched controls. Tested thrombophilic mechanisms were either genetic (activated protein C [APC] resistance; anti-thrombin III deficiency [ATIII]; protein C or protein S deficiency [PC, PS]) or acquired (lupus anti-coagulant [LAC]/anti-cardiolipin antibodies [ACA]; subsequent diagnosis of cancer). Twenty-nine DVT patients attended for full studies. The remaining 25 were interviewed by phone and none had a reported neoplastic disease, confirmed by their hospital records and the National Cancer Registry. These patients' demographics, risk factors and subsequent course were similar in all respects to the studied group. In the control group, APC resistance was the only coagulopathy found (1/25, 4%), and it was also the most common abnormality among DVT patients (8/29, 28%) (p = 0.009). Three DVT patients had LAC/ACA (10%) and one each, ATIII, PC and PS deficiencies (3.3% each). No malignancy was encountered during a follow-up of 7.9 +/- 5.7 years. Circumstantial risk factors were found in 52% of the patients, 21% had a family history of DVT, and 41% had recurrent DVT. These characteristics were not significantly different when DVT patients with and without coagulopathy were compared.
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PMID:Causes and outcome of deep-vein thrombosis in otherwise-healthy patients under 50 years. 930 63

We have established a system for etiological analysis of thrombophilia which includes assays of antithrombin III, protein C, protein S, plasminogen, fibrinogen, heparin cofactor II and lupus anticoagulants as well as gene analysis. The analysis conducted on 115 patients with venous thrombosis, arterial thrombosis and small vessel thrombosis revealed that forty-one patients(36% of the examined patients) were accompanied with decreased activities of protein S, protein C, antithrombin III and plasminogen. Eleven candidate causal mutations were found by gene analysis. These studies indicate that a comprehensive examination is instrumental in identifying and confirming the etiology in patients with thrombophilia.
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PMID:[Etiological analysis of thrombophilia]. 939 41

Sixteen patients with Moyamoya disease and four with quasi-Moyamoya disease were investigated in order to elucidate the presence of thrombophilia. The assay system for diagnosing thrombophilia consisted of assessing both the activity and antigen levels of antithrombin III, protein C, protein S, fibrinogen and plasminogen as well as detecting lupus anticoagulants. The analysis revealed that one third (four definite cases and three quasi-cases) of the examined patients demonstrated either congenital or acquired thrombotic tendency. Protein C deficiency was found in two definite cases and in two quasi-cases among whom one quasi-case was identified to have a hereditary type I Protein C deficiency. Protein S deficiency was found in one definite case and in one quasi-case. Type II plasminogen deficiency was found in one quasi-case, and lupus anticoagulant was present in one quasi-case. Based on these findings, an evaluation of thrombophilia should thus be performed when both diagnosing and treating suspected cases of Moyamoya disease.
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PMID:Thrombophilia found in patients with moyamoya disease. 940 44

The pathophysiological basis of blood coagulation includes hemostatic causes and thrombophilia (protein C deficiency, protein S deficiency, APC resistance, plasminogen deficiency, antithrombin III deficiency, hyperhomocystinemia, lupus anticoagulans and anticardiolipin antibodies). The effect of female sexual steroids on coagulation has been observed: ethinyl estradiol produced an increased risk of thromboembolism. Also, there was a pronounced increase of fibrin division products among users of higher EE doses. The effect of gestagens on coagulation was found to be contradictory. The risk of thrombosis as related to oral contraceptives (OCs) was investigated in several studies. Desogestrel and gestoden-containing OCs produced a higher incidence of thrombosis than levonorgestrel-containing pills. A WHO multinational case-control study was carried out in 21 centers and 17 countries during 1989-93, including a total of 1143 cases and 2998 controls. The risk of thrombosis was 2-3 times higher among women using gestoden or desogestrel-containing OCs than those using LNG-containing OCs. Similarly, there was a 1.58 increased risk according to a case-control study using data from England and Germany. A 1995 study of 700 medical practices in Great Britain involving 238,130 women showed increased risk for gestoden (1.8) and desogestrel (1.9). Another 1995 study used the data of 697,000 women from 398 practices in England and registered 116 cases of thromboembolism. There was a risk three times higher for all ovulation inhibitors among cases compared to controls, as well as a pregnancy risk 5.9 times higher. Nonetheless, no definitive conclusion can be drawn from all of these epidemiological studies, which could challenge the prevailing view on contraceptive behavior.
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PMID:[Contraceptive agents and risk of thrombosis]. 941 70

We analysed the results of coagulation studies in an unselected series of young adults with acute cerebral ischaemia. Our aims were (a) to determine the prevalence of coagulation disorders among these patients, (b) to investigate the relation between the presence of coagulation abnormalities and large vessel disease or potential sources of cardiac embolism and (c) to evaluate the occurrence of thrombotic events in patients with or without coagulation disorders. One hundred and twenty consecutively admitted patients (53 men, 67 women, median age 38 years, range 15-45) who presented with acute cerebral infarction (n = 89) or a transient ischaemic attack (n = 31) were evaluated. Diagnostic studies consisted of electrocardiography, echocardiography, duplex scanning, and/or angiography. Coagulation studies included activity tests of protein S, protein C, antithrombin, plasminogen, measurement of immunoglobulin G (IgG) anticardiolipin antibodies (ACLA), and a dilute prothrombin assay. Initially, 30 patients had increased ACLA titres and 28 had an abnormal dilute prothrombin assay, suggesting lupus anticoagulant. Decreased protein S, protein C and antithrombin activity were detected in 20, 3 and 3 patients, respectively, excluding patients in whom the abnormalities could be explained by the use of medication, by pregnancy or puerperium. We detected a decreased activity of plasminogen in 5 patients. The disorders could be confirmed by a second assessment in only 2 patients with a protein S deficiency, in none of the patients with a protein C or antithrombin deficiency and in 1 patient with plasminogen deficiency. However, the abnormalities persisted in 19 of 21 patients with increased anticardiolipin IgG titres and in 9 of 20 patients with lupus anticoagulant. A confirmed coagulation disorder was not associated with stroke type or vascular risk factors, but it was more common among patients with large vessel disease (odds ratio: 3.8, 95% confidence interval (CI): 1.1-12.8). Sixteen patients had a recurrent thromboembolic event, but the risk of recurrence was not increased among patients with a confirmed coagulation disorder. Our results suggest that idiopathic coagulation disorders are found in about a quarter of young stroke patients. They are difficult to predict and probably interact with other risk factors.
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PMID:Coagulation disorders in young adults with acute cerebral ischaemia. 945 24

Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing osteonecrosis (ON). Twenty-six patients with SLE were studied. Fifteen of these had ON and 11 did not. The latter were used as control subjects. Various coagulation analytes including antithrombin III (ATIII) activity, protein C activity, protein S activity, alpha 2-antiplasmin activity, anticardiolipin antibodies (aCL), plasminogen activator inhibitor (PAI-1) activity and tissue type plasminogen activator (tPA) antigen were measured using citrated plasma samples from the patients. A significant proportion (80%) of patients had at least one laboratory abnormality that has been associated with a thrombotic predisposition. ON was significantly associated with elevated levels of PAI-1 activity; it was also associated with elevated PAI-1/tPA ratio. There was no association between ON of SLE and abnormalities of the other measured coagulation analytes. These results suggest that defective fibrinolysis seems to be operative in the pathogenesis of ON associated with SLE. The defect appears to involve an imbalance between tPA and its inhibitor, PAI-1. This imbalance could represent an important risk factor in the pathogenesis of ON.
Lupus 1998
PMID:Association of osteonecrosis in systemic lupus erythematosus with abnormalities of fibrinolysis. 949 48

Congenital deficiency in coagulation inhibitors is a cause of hereditary thrombotic disease. The severity of symptoms is variable and depends on the type of deficit. In this paper, 44 children suffering from deep venous thrombosis, with a mean age of 5 years, were studied. A search for Lupus anticoagulant (LA) and coagulation inhibitor deficiency showed: 3/44 cases (6.8%) had protein S deficiency, 2/44 cases (4.5%) had protein C deficiency, 1/44 cases (2.3%) had deficiencies in both protein C and S; no cases of AT III deficiency and LA was positive in 2/44 cases (4.5%). Only 1 case of APC resistance out of 13 studied was found. Four family studies were performed and confirmed the congenital origin of the disorder.
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PMID:Thrombosis in congenital deficiencies of AT III, protein C or protein S: a study of 44 children. 949 88

The primary antiphospholipid syndrome and protein S deficiency are known hypercoagulable states predisposing to ischemic strokes. The pathogenesis of those hypercoagulable states has been independently studied and, recently, interaction between them has been proposed. A 48-year-old Hispanic man had generalized seizures 5 months after the acute onset of a left middle cerebral artery infarct. He had a strong family history of strokes. After evaluation for cardiologic, rheumatologic, hematologic and metabolic etiologies for stroke, anticardiolipin antibodies and protein S deficiency were detected. Cerebral angiography was normal. First degree relatives were evaluated and screened for these conditions. Lupus anticoagulant was detected in a sister who reported a transient hemisensory deficit. None of the relatives studied had clinical or laboratory criteria for collagen vascular diseases. Coexistence of the primary antiphospholipid syndrome and protein S deficiency, two known prothrombotic states, has rarely been reported in Hispanic adults in association with ischemic stroke.
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PMID:Coexistence of primary antiphospholipid syndrome and protein S deficiency in a Hispanic man with ischemic stroke. 952 77


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