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)

Livedoid vasculitis, a hyalinizing vasculopathy, is characterized by extensive formation of microthrombi and deposition of fibrin in the middermal vessels, which result in epidermal infarction, ulceration, and formation of stellate scars. In a prospective study of nonhealing ulcers in patients with livedoid vasculitis, we found a high incidence of anticardiolipin antibodies, lupus anticoagulants, increased levels of plasminogen activator inhibitor, and low levels of endogenous tissue plasminogen activator (t-PA) activity. This procoagulant tendency and decreased fibrinolysis may provide an explanation for the occlusive vasculopathy often noted in biopsy specimens from these patients. On the basis of these findings, we proposed that fibrinolysis with recombinant t-PA would lyse microvascular thrombi, restore circulation, and promote wound healing. In six patients who had nonhealing ulcers caused by livedoid vasculitis and in whom numerous conventional therapies had failed, low-dose t-PA (10 mg) was administered intravenously during a 4-hour period daily for 14 days. Five of the six patients had dramatic improvement; almost complete healing of the ulcers occurred during hospitalization, and tissue oxygenation, as measured by transcutaneous oximetry, increased. The one treatment failure was due to rethrombosis of the microvasculature; this patient was subsequently re-treated but with concurrent anticoagulation, and her leg ulcers healed. We conclude that daily administration of a low dose of t-PA is safe and effective treatment for nonhealing ulcers due to occlusive vasculopathy.
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PMID:Tissue plasminogen activator for treatment of livedoid vasculitis. 143 47

Human plasma contains an inhibitor of tissue factor-initiated coagulation known as the lipoprotein-associated coagulation inhibitor (LACI) or also known as the extrinsic pathway inhibitor (EPI). A competitive fluorescent immunoassay was developed to measure the plasma concentration of LACI in samples from normal individuals and patients with a variety of diseases. The LACI concentration in an adult control population varied from 60% to 160% of the mean with a mean value corresponding to 89 ng/mL or 2.25 nmol/L. Plasma LACI levels were not decreased in patients with severe chronic hepatic failure, warfarin therapy, primary pulmonary hypertension, thrombosis, or the lupus anticoagulant. Plasma LACI antigen was decreased in some, but not all patients with gram-negative bacteremia and evidence for disseminated intravascular coagulation. Plasma LACI levels were elevated in women undergoing the early stages of labor (29%), in patients receiving intravenous tissue-type plasminogen activator (45%), and in patients receiving intravenous heparin (375%). A radioligand blot of the pre- and post-heparin plasma samples shows the increase to be in a 40-Kd form of LACI. Very low levels of plasma LACI antigen were found in patients with homozygous abetalipoproteinemia and hypobetalipoproteinemia, diseases associated with low plasma levels of apolipoprotein B containing lipoproteins. Following the injection of heparin into one patient with homozygous abetalipoproteinemia, the plasma LACI antigen level increased to a level comparable with that in normal individuals after heparin treatment.
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PMID:Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. 207 76

Although Virchow postulated 100 years ago that hypercoagulability states exist, it has only been in recent years that methods of documenting hypercoagulability have been developed. These clotting tendencies can be acquired or congenital. The common causes of acquired clotting tendencies include conditions which result in tissue and cellular damage, shock, transfusion reactions, and tissue necrosis. Certain drugs and drug reactions, and certain disease states which include blood dyscrasias and cancer are also associated with clotting problems. In certain diseases such as homocystinuria, hyperlipidemia, and lupus erythematosus, abnormal clotting tendencies may also develop. Important advances in the recognition of hypercoagulability have come with the documentation that congenital clotting abnormalities exist. Moreover, these abnormalities are proving to be more common than are congenital bleeding syndromes. Patients who appear to have spontaneous clotting manifestations and are under 40 years of age should be screened for one of these abnormalities. These congenital clotting tendencies can be classified as defects in thrombosis inhibitors, dysfibrinogenemias, or defects in fibrinolysis. The first thrombotic inhibitor defect recognized was antithrombin III deficiency which was reported in 1965. Subsequently, Protein C, Protein S, and Heparin cofactor II deficiencies have been recognized as contributing to thrombotic tendencies. Dysfibrinogenemias are relatively rare and most are associated with bleeding problems; however, 11% of the abnormal fibrinogens are associated with a clotting tendency. The reason appears to be that these fibrins are resistant to fibrinolysis. The most common defects which are associated with thrombotic tendencies appear, at the present time, to be due to defects in fibrinolysis. These include hypoplasminogenemia, decreases in plasminogen activator, increases in plasminogen activator inhibitor, and Factor XII deficiency.
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PMID:Acquired and congenital clotting syndromes. 223 69

Lupus anticoagulants (LA) are IgG or IgM antibodies against phospholipids which in vivo represent an important thrombophilic factor despite their in vitro anticoagulant activity. We investigated the fibrinolytic system of 20 patients with connective tissue disease and positive LA, compared to a control group of 24 age- and disease-matched patients without LA. There was no statistically significant difference of alpha 2-antiplasmin, plasminogen, fibrinogen, t-PA activity, D-dimers and heparin cofactor II, between the two groups. Although t-PA was uniformly low in both groups, plasminogen activator inhibitor activity (PAI) was significantly higher in LA cases (p less than 0.001). Increased PAI levels represent an inhibitory factor of the fibrinolytic defense mechanism, which together with other functional deviations may contribute to the thrombophilic tendency of LA patients.
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PMID:Impaired fibrinolysis as an essential contribution to thrombosis in patients with lupus anticoagulant. 250 94

We investigated the effect of plasma and serum from 10 subjects with the lupus anticoagulant and thrombosis and 9 normal subjects on the secretion of tissue-type plasminogen activator (t-PA) and its rapid inhibitor (type 1 plasminogen activator inhibitor, or PAI-1) by cultured human endothelial cells. Confluent monolayers of human umbilical vein endothelial cells were incubated for 48 hours with plasma or serum diluted ten-fold in serum-free endothelial cell growth medium, and the secretion of t-PA and PAI-1 measured by enzyme-linked immunosorbent assay. No consistent differences in mean t-PA and PAI-1 release were found between cells exposed to normal plasma or serum and plasma or serum from subjects with the lupus anticoagulant and thrombosis. No plasma or serum sample produced consistent inhibition of t-PA release or stimulation of PAI-1 release (defined as t-PA levels less than the mean minus two standard deviations for normal subjects, and PAI-1 levels greater than the mean plus two standard deviations for normal subjects, respectively). These findings do not support a role for altered endothelial fibrinolytic activity in the pathogenesis of thrombosis in subjects with the lupus anticoagulant, and are consistent with previous observations that these subjects have normal fibrinolytic activity in vivo.
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PMID:Effect of the lupus anticoagulant on endothelial fibrinolytic activity in vitro. 250 1

The clinical and serological findings in 13 patients with myocardial infarction and antiphospholipid antibodies (the 'lupus anticoagulant', antibodies to cardiolipin, antibodies to phosphatidylethanolamine (one patient] seen by our unit and other units from 1984 to 1989, are presented (eight males and five females, ages ranging from 20 to 52 years). Five suffered myocardial infarction before the age of 30; four of these five were in their early 20s. Other risk factors such as excessive smoking (greater than 20 cigarettes a day) (two patients), long-term treatment with steroid (one) and use of oral contraceptives (one) were present. One patient had demonstrated a plasminogen activator deficiency and one a deficiency of protein C. Two patients developed myocardial infarction six to eight weeks after warfarin was discontinued for recurrent deep vein thrombosis. Six patients had SLE as defined by the revised 1982 criteria, three suffered from 'lupus-like' disease, while four patients conformed to a 'primary' antiphospholipid syndrome.
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PMID:Myocardial infarction and antiphospholipid antibodies in SLE and related disorders. 251 55

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

From the age of 17 a young man had recurrent venous thrombosis, with pulmonary embolism on two occasions. Laboratory investigations showed increased DNA binding, thrombocytopenia, positive antinuclear antibodies, and immunoglobulin A deficiency. A plasminogen activator deficiency was suspected because the euglobulin lysis time was considerably prolonged. Variant lupus was diagnosed. He had a severe myocardial infarct at the age of 20 and subsequent investigations showed the presence in serum of the lupus anticoagulant and antibodies to cardiolipin. The presence of these antiphospholipid antibodies explains the features of his illness and establishes that this case fits into a subset of systemic lupus erythematosus characterised by thrombotic events.
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PMID:Myocardial infarction in a young man with systemic lupus erythematosus, deep vein thrombosis, and antibodies to phospholipid. 308 42

In systemic lupus erythematosus (SLE) the lupus anticoagulant is known to be associated with thrombosis. However, this anticoagulant only occurs in a small percentage of patients. Histopathological studies suggest a more generalized thrombotic tendency with platelets and fibrin within the microvasculature. Fibrinogen is elevated in SLE and this may lead to the fibrin deposition described. We wondered if decreased fibrinolysis contributed to this and we infused desamino D-arginine vasopressin (DDAVP) into ten patients with SLE and eight controls. DDAVP stimulates endothelial production of plasminogen activator (PA) and factor VIII. Baseline results showed a significant decrease in PA activity with a concomitant increase in fibrinogen in SLE. The t-PA and inhibitor levels were normal but factor VIII was increased. After infusion of DDAVP, results indicated that, despite baseline results, SLE patients were able to respond to stimulation and the increase in PA activity produced a decrease in plasma fibrinogen levels. These findings may have therapeutic implications.
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PMID:Fibrinolysis in systemic lupus erythematosus: effect of desamino D-arginine vasopressin infusion. 311 77

Fibrinolysis was evaluated in 16 women with SLE, who were divided into three groups of increasing disease severity according to their past history, and in 10 normal subjects. Fibrinolysis parameters assessed were tissue-type plasminogen activator (t-PA) activity in plasma and in euglobulin fractions and rapid plasminogen activator inhibitor activity. All parameters were evaluated before and after venous occlusion to assess endothelial cell t-PA release in response to localized anoxia. Markers of deficient fibrinolysis were persistently undetectable t-PA activity and increased rapid plasminogen activator inhibitor activity after venous occlusion. Defective fibrinolysis was correlated with disease severity; it was noted only in patients with severe or moderate disease and in no patients with mild disease or in controls. Fibrinolysis abnormalities were independent of disease activity, suggesting that vascular endothelium injuries occurring during flare-ups persist during inactive phases of the disease. No correlation was found between fibrinolysis abnormalities and disease duration, corticosteroid administration, or the presence of lupus anticoagulant or anticardiolipin antibodies. These data support the hypothesis of parallelism between the severity of vascular injuries, suggested by deficient fibrinolysis, and the severity of clinical manifestations in SLE.
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PMID:Fibrinolysis abnormalities in systemic lupus erythematosus and their relation to vasculitis. 312 85


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