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

The dilute tissue thromboplastin inhibition (DTTI) test (Schleider et al, 1976) is a sensitive but non-specific test for lupus anticoagulant (LA). False positive results are seen in patients with clotting factor deficiency involving the extrinsic pathway and also in some patients with specific factor inhibitors (Triplett et al, 1983; Rosove et al, 1986). Since the effect of LA is phospholipid dependent but those of factor deficiency and specific inhibitors are not, we analyse the test results by comparing the degree of inhibition using different dilutions of tissue thromboplastin and express it as the DTTI index. This is defined as the clotting time ratio with 0.2% tissue thromboplastin divided by the clotting time ratio with 2% tissue thromboplastin. We also perform a dilute tissue thromboplastin time with platelet substitution to see if this could neutralize the inhibition caused by LA. Both of these modifications can reliably distinguish LA from other conditions associated with prolonged APTT better than the original DTTI test.
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PMID:The reappraisal of dilute tissue thromboplastin inhibition test in the diagnosis of lupus anticoagulant. 250 25

Circulating antibodies to negatively-charged phospholipids have been implicated in the genesis of adverse pregnancy outcomes. However, it has yet to be established that these antibodies are causative or that they are invariably associated with untoward perinatal outcomes. To address this issue, the prevalence of lupus anticoagulant and anticardiolipin antibodies was recorded in a low-risk obstetric population, and the outcome of untreated pregnancies were evaluated. Two of 737 patients (0.27%) had lupus anticoagulant documented by a prolonged activated partial thromboplastin time that did not correct this mixing studies. In comparison, greatly elevated concentrations of immunoglobulin M-anticardiolipin antibodies or immunoglobulin G-anticardiolipin antibodies were identified in 16/737 (2.2%) patients by means of an enzyme-linked immunosorbent assay. Spontaneous abortions occurred in both lupus anticoagulant-positive patients, suggesting that the activated partial thromboplastin time used was a relatively insensitive but specific marker for antiphospholipid antibody-associated adverse pregnancy outcomes. In contrast, although 12 of 16 anticardiolipin antibodies-positive pregnancies were complicated by perinatal loss, preterm delivery, or fetal growth retardation, four patients had uncomplicated pregnancies. Moreover, the distribution of anticardiolipin antibodies concentrations in these four patients was not clustered among the lowest anticardiolipin antibodies values, and anticardiolipin antibodies concentrations correlated weakly with adverse outcomes. These findings suggest that antiphospholipid antibodies are related to adverse pregnancy outcomes in a complex fashion and that therapy is not always required for acceptable outcomes in patients without other risk factors.
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PMID:The prevalence and biologic significance of lupus anticoagulant and anticardiolipin antibodies in a general obstetric population. 238 77

The pathogenesis of avascular necrosis of bone (ANB) was investigated in 111 patients with systemic lupus erythematosus (SLE) (24 with ANB, 87 without ANB); patients' ages, corticosteroid treatment, clinical and laboratory features associated with SLE, and haemostatic profiles were all taken into account. The mean ages of patients with and without ANB at the time of diagnosis of SLE was 24.1 and 31.2 years respectively. The mean maximal daily dose of prednisolone in the group with ANB was 50.8 mg, which was significantly higher than the dose (41.8 mg) in the group without ANB. Disease features of SLE, such as Raynaud's phenomenon, hyperlipidaemia, nephrotic syndrome, hypertension, and disease activity, were not found to be related to ANB. The percentage of patients who had lupus anticoagulant as well as a shorter activated partial thromboplastin time was greater in those with ANB than in those without. Multiple factors may be involved in the pathogenesis of ANB in SLE, and it is suggested that haemostatic abnormalities, which could be influenced by corticosteroids and young ages, play some part in the development of ANB.
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PMID:Avascular necrosis of bone in systemic lupus erythematosus: possible role of haemostatic abnormalities. 250 41

Lupus-like anticoagulants (LLA), lupus anticoagulant and/or anticardiolipin antibody, are increasingly recognized in association with venous and arterial thrombotic events. We recently reviewed our experience with patients undergoing revascularization for lower-limb ischemia who were found to have LLA. Nine patients had LLA based on a prolongation of the partial thromboplastin time or by anticardiolipin assay by an enzyme-linked immunosorbent assay system. The ages of the patients ranged from 23 to 57 years. There were seven (78%) men, six (67%) blacks, two (22%) diabetic patients, and three (33%) hypertensive patients. One patient had systemic lupus erythematosus. All patients except one were cigarette smokers. Four patients had concurrent regulatory protein abnormalities: three protein C deficiencies, one protein S deficiency, and one plasminogen deficiency. The nine patients had 10 lower-extremity arterial reconstructions with two postoperative failures within 30 days. Patients were anticoagulated with heparin or aspirin after all but one operation. Patients at risk were identified on the basis of age (less than 51 years), unexplained early graft thrombosis, or history of venous or arterial thrombotic events. This group of patients is believed to be at risk for early postoperative thrombosis. Postoperative anticoagulation after revascularization for patients with LLA may be beneficial.
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PMID:Lupus-like anticoagulants and lower extremity arterial occlusive disease. 250 7

We report studies of the validity and clinical application of a new amidolytic method for evaluating the activated partial thromboplastin time (APTT) compared with a conventional clotting method. The results with the two methods were well correlated for normal plasma and plasma from hemophilia patients. Congenital deficiencies of of the intrinsic coagulation pathway other than hypo- and dysfibrinogenemia detected by the amidolytic method agreed with those detected by the clotting APTT. The results with the two methods for plasma from patients under heparin treatment were statistically different, suggesting a lesser sensitivity of the amidolytic method to heparinization. The use of the amidolytic APTT reagent in combination with factor VIII and IX deficient plasma allowed the measurement of both factors. The results obtained with normal and hemophilic plasma were in agreement with those obtained with the one-stage clotting method in all except two occasions. Even though the amidolytic method demonstrated the presence of the lupus anticoagulant in the majority of tested samples of known lupus subjects, it was less sensitive to the abnormality than the clotting method.
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PMID:Automated amidolytic method for evaluating the activated partial thromboplastin time compared with a conventional coagulation method. 250 8

In three patients with monoclonal gammopathies: a case of multiple myeloma, a case of monoclonal gammopathy of uncertain significance (MGUS) and a case of monoclonal gammopathy associated with lymphocytic lymphoma, we found the presence of a circulating lupus-like anticoagulant. Coagulative studies showed that the paraproteins: an IgG3k, an IgG1k and an IgMlambda, were responsible for the anticoagulant activity by interacting with the thromboplastin phospholipids. Using isoelectrofocusing we demonstrated that the three monoclonal immunoglobulins had a strong basic charge which may have contributed to determining their interaction with the acidic thromboplastin phospholipids. The binding of various phospholipids to the monoclonal proteins was assessed by the fluorescence quenching method which showed heterogeneous specificity. In order to establish whether the electrical charge is also relevant in cases with polyclonal lupus anticoagulant, the polyclonal immunoglobulins were fractionated according to their charge. The strongest inhibitor activity was found in the most basic immunoglobulins. Monoclonal lupus-like anticoagulants represent useful tools for investigating the heterogeneous world of polyclonal lupus-like anticoagulants.
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PMID:Study of three patients with monoclonal gammopathies and 'lupus-like' anticoagulants. 251 Aug 15

The association of lupus anticoagulant antibodies with thrombosis, thrombocytopenia, and multiple spontaneous abortions underlines the importance of diagnostic assays which are able to distinguish these antibodies from anti-factor antibodies and factor deficiencies, as all three prolong in vitro coagulation assays measuring activated partial thromboplastin time (APTT). Heparin also prolongs the APTT assay and often interferes with the detection of lupus anticoagulant activity. The present study describes a direct and simple dilute APTT assay in which plasma is preincubated with hexagonal (II) phase phosphatidyl ethanolamine (PE). Using this system, the lupus anticoagulant antibody activity of 10 randomly selected plasmas from SLE patients was inhibited by 81.2-99.5%, while prolongation of the APTT assay by 6 different anti-factor antibody-containing plasmas, 5 factor deficient plasmas, and 6 heparin-containing plasmas remained unaffected. Inhibition was dependent on epitopes exposed when PE was presented in the hexagonal (II) phase. This data suggests that hexagonal (II) PE is specifically recognized by lupus anticoagulant antibodies in SLE patients and may play a role in the etiology of the disease.
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PMID:Distinguishing plasma lupus anticoagulants from anti-factor antibodies using hexagonal (II) phase phospholipids. 251 78

The activated partial thromboplastin time (APTT) is a commonly performed laboratory procedure which is used for multiple purposes including monitoring of heparin therapy, detection of coagulation factor deficiency, and detection of lupus anticoagulants. Among the hereditary coagulation deficiencies, factor VIII and factor IX are the most common. APTT reagents differ widely in both their sensitivity to factor VIII and factor IX deficiencies as well as their responsiveness. Sensitivity may be defined as the ability to identify a deficiency state while responsiveness is indicated by the degree of prolongation of the APTT result as compared to the upper limit of normal. Reagents may be both sensitive and responsive or alternatively sensitive and relatively nonresponsive. Consequently, it is extremely important for each laboratory to carefully identify the upper limit of the normal range. A variety of preanalytical variables will also effect the sensitivity of the APTT to factor deficiency states. These variables include specimen handling and the preparation of platelet poor plasma. The instrument effect is also of importance. Selection of the reagent tends to have the most impact on sensitivity and responsiveness while instrumentation affects the precision of a given APTT. The composition and concentration of phospholipid in APTT reagents does have an effect on reagent responsiveness and sensitivity. Sensitivity to factor deficiencies does not necessarily parallel sensitivity to lupus anticoagulants.
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PMID:Use of the activated partial thromboplastin time for the diagnosis of congenital coagulation disorders: problems and possible solutions. 251 50

In hemostasis testing the development of chromogenic substrates provides an alternative to the traditional methods based on the detection of forming clots. The new technology has often replaced the clotting tests, especially in the area of single clotting factor and inhibitor assay, less frequently for global screening tests. We report studies of the validity and clinical application of two reagents for activated partial thromboplastin time (APTT) testing with chromogenic substrates in comparison with the conventional clotting method. Congenital deficiencies of the intrinsic coagulation pathway, other than hypo- and dysfibrinogenemia detected by chromogenic APTT, agreed with those detected by the clotting APTT. The results with the two methods for plasma under heparin treatment suggest a lesser responsiveness of the chromogenic methods to heparinization. The chromogenic methods demonstrated the presence of the lupus anticoagulant in the majority of tested samples of known lupus subjects, but with a lower responsiveness than the clotting method. In conclusion, we found chromogenic APTT suitable for hemostasis testing because it generally gives the same information as the conventional clotting method with the exception of heparin monitoring and lupus anticoagulant detection, where an improved sensitivity would be desirable.
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PMID:Chromogenic substrates for activated partial thromboplastin time testing: are they worth using? 251 51

The lupus anticoagulant may be defined as an immunoglobulin (IgG, IgM or both) which interferes with one or more of the in vitro phospholipid-dependent tests of coagulation. For many years, lupus anticoagulants were regarded as a laboratory nuisance; consequently, reagents were often selected on the basis of insensitivity to lupus anticoagulants. Recently, lupus anticoagulants have been associated with a variety of clinical conditions including recurrent thromboembolic events (both arterial and venous), obstetrical complications including fetal death and spontaneous abortion, and a variety of hematologic and neurologic complications. As a result, many laboratories are now being asked to identify the presence of lupus anticoagulants in selected patient populations. In addition to assays for lupus anticoagulants, there are immunologic assays designed to detect phospholipid antibodies using solid phase systems (RIA or ELISA). A variety of screening tests have been designed to enhance sensitivity to lupus anticoagulants. Test systems with decreased amounts of phospholipid (phosphatidylserine) appear to be most sensitive to lupus anticoagulants. Of the various tests used, the activated partial thromboplastin time (APTT) appears to be most sensitive. The sensitivity of any screening test system is inversely proportional to the residual platelets in the patient sample. APTT reagents differ widely in their sensitivity to lupus anticoagulants. The dilute Russell viper venom time is also highly dependent on the choice and concentration of phospholipid with respect to its sensitivity. Once an abnormality of a screening test has been identified, it is necessary to prove the abnormal result is due to the presence of an inhibitor. This step in the diagnosis may utilize either mixing studies or plasma agarose gels. The final step in the diagnosis of lupus anticoagulants is the demonstration of phospholipid specificity of the inhibitor. Two approaches have been utilized: 1. test systems designed to enhance anticoagulant effect (phospholipid-depleted), and 2. test systems with increased or altered phospholipids which will bypass or neutralize the anticoagulant.
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PMID:Screening for the lupus anticoagulant. 251 52


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