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)

Most causes of abnormal bleeding can be determined from a complete blood count including platelet count and bleeding, prothrombin, activated partial thromboplastin, and thrombin times. Occasionally, further evaluation is necessary, such as tests of factor XIII function, fibrinolysis, and vascular integrity. Possible diagnoses include disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, vitamin K deficiency, von Willebrand's disease, heparin-induced thrombocytopenia, acquired inhibitors of factor VIII, lupus anticoagulants, and coagulation disorders related to the acquired immunodeficiency syndrome.
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PMID:Laboratory evaluation of a bleeding patient. 266 Apr 7

In a prospective study assessing haemostatic functions, the activated partial thromboplastin time was prolonged in 134 out of 10,229 patients studied, without an increase in the prothrombin or thrombin times; this abnormality persisted in only 37 of them on a new blood sample. A retrospective analysis was made of 265 patients who had such an isolated prolongation of the activated partial thromboplastin time on two successive blood samples: the causal abnormality remained unexplained in 135 patients; a well defined coagulation disorder without abnormal bleeding tendency was present in 110 patients (1 severe factor XII deficiency, 58 partial factor XI or XII deficiencies and 51 lupus anticoagulants); a bleeding disorder was diagnosed in 20 patients (8 haemophilias, 8 Von Willebrand's diseases, 4 factor VIII inhibitors). The well-iron efficacy of the activated partial thromboplastin time for detecting coagulation abnormalities is counter-balanced by some disadvantages such as the delay for biologic conclusions. In the preoperative assessment of haemostatic functions, rather than taking a routine approach, it would seem better to determine for each patient the need and the extent of biological testing according to the type of planned surgery, the clinical status of the patient and possible bleeding symptoms.
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PMID:[Successes and failures of the activated partial thromboplastin time in the preoperative evaluation]. 308 57

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

To see whether or not the fibrin-stabilizing factor is involved in the pathogenesis of renal damage, we analyzed by IF the glomerular deposition of factor XIII (subunits A and S) in 161 patients with various renal diseases. In 4 out of 5 cases of thrombotic microangiopathy (80%), F XIII deposits were found in a continuous subendothelial pattern, in association with deposition of fibrinogen and FDP, suggesting the occurrence of intraglomerular coagulation. In 22 out of 45 patients with membranous GN (idiopathic or SLE-associated), F XIII deposits were found along the capillary walls in a subepithelial location. These findings were not correlated with the presence of particular histological or clinical features, nor with IF positive for fibrinogen, FDP and factor VIII, suggesting alternative pathways of fibrin formation or local collagen synthesis. Finally, in proliferative GN, either idiopathic (acute post-infectious and membranoproliferative) or systemic (SLE and vasculitis), as in other glomerular and non-glomerular diseases, the presence of F XIII deposits was negligible, even in cases positive for fibrinogen, FDP and factor VIII.
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PMID:Deposition of fibrin-stabilizing factor (F XIIIA and S), fibrinogen-related antigens, fibrinogen degradation products (FDPd and FDPe) and antihemolytic factor (F VIII) in renal disease: analysis of 161 cases by immunofluorescence microscopy. 311 91

Several antibody fractions and sera from patients with rheumatoid arthritis, systemic lupus erythematosus and chronic idiopathic thrombocytopenic purpura were examined for their ability to bind to normal platelets using immunofluorescent staining techniques. Platelet aggregometry was used to study the activating capacity of the samples. Both C1q, C1s, C1 inactivator, fibrinogen, factor VIII-related antigen, alpha 1-acid glycoprotein, alpha 1-antitrypsin, beta 2-microglobulin and isoantigens A and B, as well as fibronectin and plasminogen were found on the platelet surface. Only antibodies to C1q, C1s and beta 2-microglobulin were able to induce platelet aggregation. Sera containing immune complexes or platelet autoantibodies revealed positive surface staining for IgG, or for IgG and IgM. There sera also induced aggregation of platelets. Sera not containing immune complexes or autoantibodies gave negative staining and aggregation results. Thus, only some of the ligand receptor interactions were able to induce platelet aggregation.
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PMID:Studies on the binding of proteins to the human platelet surface: relation to platelet activation. 390 92

In an earlier report on the kidney in systemic lupus erythematosus (SLE), we described a subset of patients with circulating anticoagulants; many had glomerular and arteriolar thrombosis in the absence of necrosis and subendothelial deposits. The present study extends these observations to a larger group of patients with SLE and a circulating anticoagulant, and compares its findings with those in patients with SLE without evidence of an anticoagulant. It demonstrates (1) a higher prevalence of clinically recognizable thrombotic events in the venous and arterial circulations in patients with SLE and a detectable anticoagulant; (2) a probable shortening in life span; (3) a higher prevalence of glomerular thrombi; (4) elevated levels of factor VIII antigen and von Willebrand factor; and (5) significantly lower platelet counts and decreased in vitro platelet aggregation in response to adenosine diphosphate, epinephrine, and collagen. Since prednisone treatment often results in improvement or disappearance of a prolonged partial thromboplastin time, the test most commonly used for screening of a circulating anticoagulant, we suggest that the prevalence of this abnormality may be underestimated in patients with SLE.
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PMID:Thrombosis in systemic lupus erythematosus. Relation to the presence of circulating anticoagulants. 392 65

Lupus anticoagulants are spontaneously occurring antibodies with specificity for negatively charged phospholipids. The plasma of a patient with such a polyclonal antibody of IgM type demonstrated low levels of factor VIII coagulant activity (VIII:C) and factors IX, XI and XII when analyzed by biologic clotting assays, whereas in immunochemical assays, normal levels of VIII coagulant antigen and factor IX were obtained. After immunoadsorption of patient plasma with anti-IgM Sepharose, normal biologic activities were demonstrated in clotting assays for VIII:C, factors IX, XI, and XII. The addition of the patient's isolated IgM to normal plasma resulted in grossly abnormal results in these coagulation assays, and a pattern similar to that of the patient's plasma was obtained. The inhibitory effect of the patient's lupus anticoagulant on blood coagulation was demonstrated also in platelet-rich plasma. The results of the clotting assays indicated that the anticoagulant inhibited several of the reactions in the blood coagulation cascade. The availability of purified components made it possible to demonstrate an inhibiting effect on the activation of prothrombin by factor Xa in the presence of isolated platelets, as well as in a system where purified factor V and well defined phospholipid vesicles were substituted for the platelets.
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PMID:Inhibition of platelet prothrombinase activity by a lupus anticoagulant. 640 49

The experience of 118 coagulation specialists in the treatment of 215 non-hemophilic patients with inhibitors to factor VIII:C was recently reviewed. In approximately half these patients there were no illnesses which may have predisposed to inhibitor formation, while "auto-immune" disorders such as rheumatoid arthritis and systemic lupus erythematosus were present in 18%. Major bleeding was reported in 87% of the patients, and 22% died as a consequence of having the inhibitor. While inhibitors in a few patients, particularly those that developed in association with pregnancy, disappeared without treatment, most patients were given prednisone in doses of up to 2 mg/kg per day. This therapy was most effective in patients without associated disorders, but disappearance of the inhibitor in patients with rheumatoid arthritis usually occurred only when cyclophosphamide or azathioprine was added to the therapeutic regimen. Subjects with inhibitor titers in excess of 10 Bethesda Units were usually refractory to all therapeutic modalities. The management of acute bleeding episodes in the patient with an inhibitor has been the subject of a number of recent reports. Successful stratagems have included intensive plasmapheresis combined with massive infusion of antihemophilic factor concentrates, the use of porcine factor VIII concentrates, and the administration of clotting factor concentrates which bypass the locus of factor VIII participation in clotting. All of these methods expose the patient to potential serious side-effects, and the ultimate solution to the problem of the development of factor VIII inhibitors will require insights into the reasons for the production of these antibodies and measures to regulate aberrant immune processes.
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PMID:The management of factor VIII inhibitors in non-hemophilic patients. 643 38

Identification of spurious coagulation factor deficiencies that are known to occur in association with lupus-like anticoagulants (LLACs) requires the use of cumbersome laboratory procedures. To determine whether single-stage assays employing the APTT system may be used to identify such artifacts, we measured multiple clotting factor levels by several techniques in plasma of six patients with typical LLACs. While normal activities of factors VIII, IX, XI and XII were measured in only 4/24 APTT assays (17%) employing human plasma substrate, normal factor activities were present in all 24 APTT assays employing bovine, canine or rabbit plasma substrate. Normal factor II, V and X activities were recorded in all but one case in assays that utilized a modified Stypven time, while normal factor VIII levels were determined in 5/6 plasmas when the thromboplastin generation test was employed. These results indicate that the use of heterologous plasma substrates in the APTT system may provide a simple method to identify such coagulation factor "deficiencies".
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PMID:Correction of clotting factor "deficiencies" in plasma from patients with lupus-like anticoagulants. 643 3

Haemorrhagic complications, though uncommon in SLE, may be life-threatening in individual patients, and they require treatment along appropriate lines. Thrombotic problems are more commonly encountered, and are a significant cause of morbidity and mortality. Not only is clinical thrombosis important in SLE, but there is increasing evidence that low-grade coagulopathy contributes substantially to many of the pathological features seen in lupus. The mechanisms involved in the pathogenesis of thrombosis have been discussed and their possible interrelationship is summarized in Figure 4, though it remains speculation that low-grade coagulopathy predisposes to clinical thrombosis. Several of these mechanisms may be operating during periods of disease activity; this was suggested in a recent study of clinical and histological features in SLE (Kant et al, 1981). The study was designed to look at the prevalence of glomerular thrombosis in SLE, and its significance as a histological feature. A striking association was observed between the presence of a circulating anticoagulant and the appearance of glomerular thrombosis on renal biopsy. Also, factor VIII levels were significantly increased and circulating platelets decreased in association with "active' histological features. On later re-biopsy glomerulosclerosis was a much more common finding if the first biopsy showed thrombosis, suggesting that thrombosis is a marker of more severe disease activity and inflammation. A greater understanding of the mechanisms promoting thrombosis will undoubtedly provide insight into the pathogenesis of SLE, as well as suggesting new therapeutic possibilities.
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PMID:The clotting defect in SLE. 681 Nov 89


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