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)

Since most patients with thrombophilia in Israel are referred for diagnosis to our center, it was possible to estimate the relative frequency of the hereditary disorders leading to thrombophilia. 107 unrelated patients were evaluated over 4 years. Diagnoses were established in 23 patients (21.5%) while in 84 (78.5%) no abnormality was detected. Antithrombin III deficiency was found in 8 patients (7.5%), dominant protein C deficiency in 6 (5.6%), recessive homozygous protein C deficiency in 1, protein S deficiency in 3 (2.8%) and dysfibrinogenemia in 1. Four additional patients (3.7%) had a lupus anticoagulant. The frequency of deep vein thrombosis and pulmonary embolism was similar in patients with and without a definite diagnosis. Thrombosis of visceral or cerebral vessels and a positive family history were more frequent among patients in whom a definite diagnosis was made. In both groups there was a substantial lag between the time of presentation of the first thrombotic episode and the time of evaluation. Since the number of referred patients with thrombophilia has gradually increased over the period of the study, it is at present impossible to establish the prevalence of the various hereditary disorders leading to thrombophilia in the population.
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PMID:The relative frequency of hereditary thrombotic disorders among 107 patients with thrombophilia in Israel. 252 86

A 16-year-old boy had recurrent venous thromboses and pulmonary thromboembolism that caused him pulmonary hypertension. He also had livedo reticularis, thrombocytopenia and high titer IgG antiphospholipid (cardiolipin) antibodies. In the absence of clinical and laboratory evidence of SLE, he was considered to have a primary antiphospholipid syndrome. Coagulation studies revealed a functional deficiency of protein C although it was present in normal antigenic amounts. Since both his parents had normal functional and antigenic protein C findings, his deficiency was considered acquired. The reactivity of the anticardiolipin antibodies could be decreased in a dose dependent fashion when preincubated with increasing amounts of thrombomodulin, a protein required for protein C activation at the endothelial cell membrane. This interaction of antiphospholipid antibodies with thrombomodulin may help explain the occurrence of thrombosis in some patients with antiphospholipid antibodies, despite the behavior in vitro of these antibodies as circulating anticoagulants.
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PMID:Acquired protein C deficiency in a patient with primary antiphospholipid syndrome. Relationship to reactivity of anticardiolipin antibody with thrombomodulin. 254 43

We have investigated the effect of purified immunoglobulin G (IgG) on endothelial cell functions in 16 patients with lupus anticoagulant, 9 of whom had systemic lupus erythematosus (SLE). Spontaneous or thrombin-stimulated secretion of prostacyclin (PGI2) by cultured human endothelial cells from umbilical cord vein (HUVEC) was not inhibited by the patient's IgG. Nor was spontaneous release of tissue plasminogen activator (t-PA) or of its inhibitor (PAI) modified in the presence of patient's IgG. The rate of activation of purified protein C (PC) by HUVEC in the presence of thrombin was significantly lowered by patient's IgG or Fab' fragment (inhibition of 43%). Neutralization of this effect was obtained by incubation of a greater quantity of phospholipids (phosphatidylcholine, phosphatidylserine) with the patient's IgG. Activation of PC was also performed using purified rabbit thrombomodulin (TM) and a similar inhibition of the patient IgG was observed (inhibition of 48%) but the activation of Gla-domainless PC was not modified.
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PMID:Effect of lupus anticoagulant on antithrombogenic properties of endothelial cells--inhibition of thrombomodulin-dependent protein C activation. 284 52

An anticoagulant activity was isolated from the plasma of a patient with a strong lupus-like anticoagulant using gel filtration by high performance liquid chromatography. IgM were detected in this anticoagulant fraction which exhibited specificity towards 50% phosphatidylcholine - 50% phosphatidylserine vesicles and cardiolipin. These phospholipids were able to produce an apparent 3-fold enhancement of purified human protein C activation by human alpha-thrombin in the presence of purified human placenta thrombomodulin. In the absence of phospholipid, the anticoagulant fraction had no effect on thrombomodulin activity. The anticoagulant fraction could neutralize the enhancement of thrombomodulin activity by phospholipid in a dose-dependent manner. This study suggests that the neutralization of phospholipid might result in a reduced activation of protein C which could be responsible for the occurrence of thrombotic complications in a proportion of patients with lupus anticoagulants.
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PMID:An IgM lupus anticoagulant that neutralizes the enhancing effect of phospholipid on purified endothelial thrombomodulin activity--a mechanism for thrombosis. 301 55

The lupus anticoagulant is a risk factor of thrombosis. The non thrombogenic endothelial surface could be a target for the lupus anticoagulant. We have investigated the effect of purified immunoglobulins G of five patients with LA on the thrombomodulin activity of cultured human endothelial cells from umbilical cord vein. The rate of activation of purified protein C (PC) (30 nM) by the endothelial cells in the presence of thrombin (0.1 U/dish) has been measured by hydrolysis of substrate S 2366. Activated PC has been 7.37 +/- 0.78 pmoles X ml-1 X h-1 in the presence of buffer and 7.2 +/- 0.78 pmoles X ml-1 X h-1 in the presence of control IgG (2 mg/dish). Heat aggregated IgG did not induce any significant change. Patient's IgG lowered significantly the rate of PC activation (4.86 +/- 1.04 pmoles X ml-1 X h-1, p less than 0.001). Fab fragment from two of these patient's IgG displayed the same inhibition. Moreover neutralization of this effect was obtained by addition of phospholipids (70% phosphatidylcholine, 30% phosphatidylserine) in excess to patient's IgG. Activation of PC has been also performed using purified rabbit thrombomodulin and a similar inhibition by patient's IgG was found. These results seem to indicate that antibodies present in the IgG fractions containing LA could be directed against phospholipids associated to thrombomodulin activity. Reduction of PC activation if present in the patients with LA could play a role in the occurrence of thrombosis.
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PMID:[Circulating lupus-type anticoagulant, a risk factor for thrombosis by inhibition of protein C activation]. 301 90

The lupus anticoagulant is usually found in the plasma of patients with systemic lupus erythematosus. Lupus anticoagulants are antibodies to phospholipids and probably to phosphodiester-linked phosphate groups. A high frequency of thrombotic events in patients with lupus anticoagulant has been reported. Nevertheless the pathogenesis of thrombosis in these patients remains unknown. Endothelium which plays a key role in the antithrombogenic-thrombogenic balance could be a target for the lupus anticoagulant and alterations of some endothelial-cell functions could be responsible for the thrombotic events. The effects of the lupus anticoagulant on the phospholipids of the protein C-thrombomodulin complex may be important although evidence of such a reaction in vivo is awaited.
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PMID:The lupus anticoagulant and its role in thrombosis. 313 12

Protein C (PC) is a vitamin K-dependent protein which functions as a physiologic anticoagulant. In the presence of another vitamin K-dependent protein, protein S, the activated form of protein C (APC) will degrade the active cofactors Va and VIIIa. Both hereditary and acquired deficiencies of PC have been associated with a predisposition to thromboembolic events. We have evaluated a commercial assay system (Stac lot Protein C) which utilizes an extract of snake venom (Protac) that directly activates protein C in vitro. Utilizing this assay, normal individuals, patients with hereditary protein C deficiency, patients who were stably anticoagulated with oral anticoagulants, and patients with lupus anticoagulants were evaluated. Significant discrepancies were noted between protein C antigen and protein C functional activity in patients receiving oral anticoagulants. In addition, patients with lupus anticoagulants may have falsely elevated values for functional protein C activity.
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PMID:Clinical application of a functional assay for protein C. 314 9

Some molecular defects of components of the coagulation or fibrinolytic system are associated with thromboembolism. One possibility is that physiologic inhibitors of the coagulation system have an abnormal function e.g. protein C, protein S, antithrombin III and cofactor II of heparin. Also a hindered activation of the fibrinolytic system may predispose to thrombosis; the impaired activation may be due to deficient synthesis and/or release of tissue-plasminogen activator, an increased level of its inhibitor or a functional defect of the plasminogen molecule. A few cases of congenital dysfibrinogenemia have been described in which the functional defects of the molecule are held responsible for recurrent thrombosis. An acquired thrombotic disorder is due to the presence of immunoglobulins which prolongs phospholipid-dependent coagulation by binding to epitopes of some phospholipids. This so-called lupus anticoagulant was originally described in patients with systemic lupus erythematosus but is a misnomer as it is more frequently encountered in patients without lupus.
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PMID:[Molecular defects of coagulation factors and of the fibrinolytic system associated with thromboembolism]. 354 55

In spite of recent advances in knowledge concerning the detailed biochemistry of blood coagulation, the diagnosis of haemostatic disturbances remains an important problem of clinical judgement in many instances. Laboratory support relies initially on a series of screening tests designed to investigate the general nature of blood clotting. Recent interest in these aspects is centred on standardization and quality assurance of methods and results. Procedures have been recommended in an attempt to unify data. Several aspects of conventional laboratory investigations have been modified and the reliability of diagnostic information has been improved. Some relatively recent findings have extended the application to coagulation studies. For example, the discovery of protein C, a potent physiological inhibitor of blood coagulation, has clarified the nature of the clotting disorder in some patients with hereditary thrombosis disease. In addition, close analysis of plasma from patients with systemic lupus erythematosus has stimulated interest in the association between the haemostatic, neurological and immunological abnormalities recorded in these patients. More recently, sophisticated techniques for the diagnosis of many coagulation factor defects have been developed. Carrier detection of the sex-linked disorders is undertaken widely with reasonable success and reliable prenatal diagnosis procedures have been established in specialized centres. Unequivocal information regarding the diagnosis of carrier status in some families is obtained by the use of gene analysis and linked polymorphisms. Precise details of the genes for several clotting factors have been recorded. Future development in this field is likely to improve the clinical course of many coagulation disorders.
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PMID:Laboratory support in the diagnosis of coagulation disorders. 389 45

The authors report their experience with 45 cases of inferior vena cava thrombosis. Diagnosis was delayed for an average of 55 days. One-third of cases were revealed by an embolic complication. Inflammatory diseases were the most common causes (Behcet disease: seven cases, systemic lupus erythematosus: 5 cases). Malignancies accounted for 20% of cases. Abnormalities of coagulation were uncommon: antithrombin III deficiency in one patient and protein C deficiency in another. Estrogen-progestogen combinations could be incriminated in 4 cases. Outcome was fatal in 20% of cases, usually as a result of the underlying disease. Functional status was good in two-thirds of patients without malignancy followed up for an average of 27 months. In 14 patients a clip was inserted to ensure total (3 cases) or partial (11 cases) interruption of vena cava blood flow because of a free thrombus and/or recurrent pulmonary embolism. Three patients had thrombectomy. After clip insertion two embolisms were recorded, one of which occurred in the immediate post-operative period.
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PMID:[Inferior caval syndromes. Apropos of 45 cases]. 632 Apr 31


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