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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a 31-year-old woman with a history of recurrent arterial thrombosis, both of whose pregnancies had resulted in intrauterine death at 23 and 24 weeks, a "lupus" anticoagulant was identified. The patient's IgG fraction, containing the lupus anticoagulant, reduced the release of prostacyclin (PGI2) from rat aorta rings or pregnant human myometrium. This inhibitory effect was abolished in the presence of arachidonic acid. The production of 6-keto-PGF1 alpha by cultured bovine endothelial cells was also decreased in the presence of the patient's IgG fraction. The plasma level of 6-keto-PGF1 alpha was reduced. An antibody in this patient may interfere with the production or release of PGI2 by the vessel wall, possibly by interfering with the availability of arachidonic acid. This mechanism could play a role in this patient's arterial disease and obstetric problems.
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PMID:Arterial thrombosis, intrauterine death and "lupus" antiocoagulant: detection of immunoglobulin interfering with prostacyclin formation. 610 1

Hypercoagulability may contribute to stroke in young adults. Lupus anticoagulants (LA) were identified in six patients (4%) of 145 young adults with cerebral infarction. The clinical features of the 6 patients in this survey plus an additional patient from another institution with LA-associated stroke are presented. Four had systemic lupus erythematosus and 3 had idiopathic LA; all had mild thrombocytopenia. In 2 patients, no other conditions associated with stroke were discovered after thorough evaluation. Recurrent arterial thrombosis occurred in 4 of 7 patients during an average of two years of follow-up. Evidence suggests that inhibition of prostacyclin formation may occur with LA, promoting a prothrombotic state.
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PMID:Cerebral infarction associated with lupus anticoagulants--preliminary report. 642 Sep 43

Two patients with lupus erythematosus and renal vein thrombosis are described. Both patients had the "lupus anti-coagulant" in their serum. It is postulated that in these patients the clotting tendency could be favoured by a cross reaction of the "lupus anti-coagulant" with phospholipids in the endothelial cell membrane, resulting in inhibition of prostacyclin release.
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PMID:Renal vein thrombosis in systemic lupus erythematosus: association with the "lupus anticoagulant". 644 40

Six women, aged 16 to 27 years old at the beginning of their illness suffered recurrent spontaneous abortion (two to eight episodes) and three of them had arteriolar venous thrombosis. These symptoms led to the finding of an antiprothrombinase type of circulating anticoagulant. In two cases, positive dissociated syphilitic serology was observed and all patients presented other haematological abnormalities: thrombocytopaenia and/or autoimmune haemolysis. The diagnosis of disseminated lupus erythematosis was established after an average period of 11 years (range 1 to 27 years) based on at least 4 of the ARA criteria (five out of six cases) and/or characteristic immunological abnormalities (five out of six cases). Thrombosis is more common in lupus when there are associated haematological abnormalities. It is probably directly related to the presence of circulating anticoagulant which inhibits the production and/or secretion of prostacyclin by the endothelial cells.
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PMID:[Recurrent abortions and circulating anticoagulant. Relation to lupic disease: 6 cases]. 651 21

Evidence exists of an association between the presence of a "lupus" anticoagulant in plasma, recurrent fetal loss, and repeated thromboembolic accidents, also in the absence of systemic lupus erythematosus. Presented is an example of this association, with morphologic and biologic studies to elucidate its pathogenesis. In the case reported, the placenta showed massive infarction. In the spiral arteries of the basal plate of the placenta, lesions of intimal thickening, fibrinoid necrosis, acute atherosis, and intraluminal thrombosis were observed. The plasma of the patient contained a lupus anticoagulant and inhibited the formation of prostacyclin by rat aortic rings. Vascular production of prostacyclin is a major natural defense mechanism against thrombosis. Lack of generation of prostacyclin may account for the decidual vasculopathy and consequent placental infarction and for the generalized thrombotic tendency of some patients with lupus anticoagulant.
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PMID:Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant. 680 84

We report the observations of 4 young women suffering from SLE witha circulatig antiprothrombinase anticoagulant. Antiprothrombinase is the most frequent circulating anticoagulant found in SLE (5 to 10 p. 100). SLE is the main aetiology for antiprothrombinase (over 50 p. 100). It is called 'lupus anticoagulant'. Some symptoms seem to be more frequent in SLE with antiprothrombinase. Such are biological signs (false positive tests for syphilis. Coombs test, thrombopenia, prothrombin deficiency) and clinical signs (venous or arterial thrombosis particularly if oestroprogestative treatment is taken, bleeding if thrombocytopenia or deficiency of prothrombin; repetitive abortion and may be neuropsychiatric signs). Antiprothrombinase is an autoantibody (IgG or IgG + M) polyclonal in SLE, with antiphospholipid activity. It could decrease the production of prostacyclin (PGI2) from free arachidonic acid derived from membrane bound phospholipids. Immunological properties of antiprothrombinase could account for clinical and biological associated signs.
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PMID:[Antiprothrombinase type of circulating anticoagulants during acute disseminated lupus erythematosus]. 698 16

Two classes of antiphospholipid antibodies (APA) are associated with adverse pregnancy outcomes. Those APA identified by immunoassays using phospholipid-coated surfaces (e.g., anticardiolipin antibodies) seem to bind to the 57 kD anticoagulant protein, beta 2-glycoprotein-I, when complexed with anionic phospholipid bilayers. Such APA may or may not prolong phospholipid-dependent clotting assays. A second class of APA are identified by their interference with phospholipid-dependent clotting assays (i.e., lupus anticoagulants). The latter bind to phospholipids present in a unique hexagonal phase either alone or complexed with prothrombin or beta 2-glycoprotein-I. There is evidence that both classes of APA are directly responsible for adverse pregnancy outcomes including spontaneous abortions, stillbirths, fetal growth retardation, thrombosis, thrombocytopenia, and preeclampsia. Putative APA-mediated pathogenic mechanisms include intervillous thrombosis, intravillous infarctions and decidual vasculopathy. The thrombogenicity of APA may result from their interference with endothelial phospholipids required for antithrombin III and protein C and S anticoagulant activity and prostacyclin synthesis and/or increased endothelial expression of the procoagulants: tissue factor, von Willebrand factor, platelet-activating factor, and plasminogen activator inhibitor type-1. Other prothrombotic properties seem to include: increased platelet aggregation, and reduced beta 2-glycoprotein-1 and annexin V anticoagulant activity. Rigorous diagnostic criteria must be applied to the detection of both classes of APA because the prevention of adverse pregnancy outcomes requires potentially hazardous anticoagulant therapy.
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PMID:The immunobiology and obstetrical consequences of antiphospholipid antibodies. 752 11

The term 'antiphospholipids' (APL) refers to heterogeneous auto-antibodies, including anticardiolipins detected by immunological methods and lupus anticoagulants detected by clotting tests. APL are currently of considerable interest, both from a clinical and a biological point of view, since their presence is associated with thromboembolic events. In this review, the authors emphasize the diversity of the clinical settings where APL are diagnosed and investigate the relationship between APL and thrombosis. The heterogeneity of APL and the lack of standard techniques make their laboratory diagnosis difficult and require the use of various types of tests. Several pathogenic mechanisms, all related to a possible effect of APL on the antithrombotic functions of vascular endothelium, have been proposed: decrease in prostacyclin synthesis, induction of procoagulant activity, inhibition of the endothelial anticoagulant functions, and impairment of fibrinolysis. Given the heterogeneity of these antibodies, it is unlikely that a single mechanism can account for their prothrombotic effect.
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PMID:[Antiphospholipid antibodies]. 780 45

Antiphospholipid antibodies are a diverse group of immunoglobulins initially thought to have specificity to phospholipid epitopes. It is apparent that autoimmune anticardiolipin antibodies require a serum cofactor beta-2-glycoprotein I (beta 2GPI) for their binding to phospholipids. Lupus anticoagulant also may bind to phospholipids by beta 2GPI or by prothrombin. The description of binding to protein-phospholipid epitopes may explain several perplexing features of these antibodies both in vitro and in vivo. Antiphospholipid antibodies have a well-established association with clinical disease--in particular thrombosis, thrombocytopenia and recurrent fetal loss. The mechanism of the predisposition to thrombosis seen with these antibodies is poorly understood. It has been suggested that they may cause endothelial dysfunction by causing increased tissue factor expression, by inhibiting prostacyclin secretion or by inhibiting fibrinolysis. Various platelet-activating activities have also been described. The evidence that antiphospholipid antibodies promote thrombosis by effects on endothelium or platelets is inconclusive. Inhibition of protein C activation, or of activated protein C action, has been demonstrated in vitro. A poor correlation between thrombosis in vivo and these inhibitory effects has been found. Beta-2-glycoprotein I has been identified as a cofactor for binding to phospholipid by thrombogenic anticardiolipin antibodies. That beta 2GPI may be a natural anticoagulant of importance remains to be proved. Inhibition by antiphospholipid antibodies of this anticoagulant function could explain the propensity to thrombosis seen in association with these antibodies.
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PMID:Antiphospholipid antibodies and thrombosis. 784

In a group of 6 patients with lupus anticoagulant (LA) and antiphospholipid (aPL) antibodies detected by ELISA overnight urine and blood were simultaneously collected. A significantly increased urinary excretion of the platelet-derived thromboxane (TX) metabolite 11-dehydro-TXB2 was found in this group, as compared to 12 healthy individuals. In contrast, a small but significant reduction of the vascular prostacyclin (PGI2) metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha was observed. To further elucidate the effect of these antibodies on platelet activation we isolated the F(ab')2 fragments from IgG of the 6 patients and 5 controls, and we evaluated the effect of these fragments on the responses of isolated normal platelets to thrombin. Patients' F(ab')2 increased platelet aggregation and serotonin release of platelets stimulated by low dose thrombin (0.01 U/ml). At threshold thrombin concentration (0.05 U/ml) an enhanced TXB2 production was also observed. In summary, our results show, in addition to the altered TXA2/PGI2 balance observed in vivo, a direct stimulatory effect of aPL antibodies on platelet activation in vitro. This effect is related to recognition of phospholipid epitopes on platelets as shown by its neutralization upon preincubation with phospholipids. This phenomenon may be relevant for the thrombotic tendency of these patients.
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PMID:Antiphospholipid antibodies enhance thrombin-induced platelet activation and thromboxane formation. 811 93


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