scholarly journals Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulant

2019 ◽  
Vol 3 (4) ◽  
pp. 695-703 ◽  
Author(s):  
Osamu Kumano ◽  
Gary W. Moore
Keyword(s):  
Lupus Anticoagulants

Relative Sensitivity of Different Tests in the Detection of Low Titer Lupus Anticoagulants

1988 ◽  
Vol 60 (02) ◽  
pp. 217-219 ◽  
Author(s):  
B Lesperance ◽  
M David ◽  
J Rauch ◽  
C Infante-Rivard ◽  
G E Rivard
Keyword(s):  
Relative Sensitivity ◽  
Fetal Outcome ◽  
Anticardiolipin Antibodies ◽  
Lupus Anticoagulants ◽  
Normal Plasma ◽  
Coagulation Tests ◽  
High Dilutions ◽  
Tissue Thromboplastin ◽  
High Concentrations ◽  
Kaolin Clotting Time

SummaryLupus anticoagulants (LA) and anticardiolipin antibodies have been strongly associated with recurrent abortion and fetal death. Because steroids have been reported to improve the fetal outcome of LA associated pregnancies, presumably by decreasing the levels of LA, it becomes desirable to have a simple and reliable test to monitor the levels of the putative antibody. To this effect, we assessed the capacity of the following coagulation tests to detect the presence of LA in serial dilutions of patient plasma with pooled normal plasma: kaolin clotting time (KCT), tissue thromboplastin inhibition test (TTIT), dilute Russell Viper venom time (DRVVT) and activated partial thromboplastin time with standard and high concentrations of phospholipids (SC and HCAPTT). All samples were also evaluated for the presence of anticardiolipin antibodies with an ELISA. The KCT was able to detect LA at a much greater dilution in normal plasma than any of the other clotting assays. The ELISA was comparable to KCT in its ability to detect high dilutions of LA.

Synchronized Inhibition of the Phospholipid Mediated Autoactivation of Factor XII in Plasma by β2-glycoprotein I and Anti-β2-glycoprotein I

1995 ◽  
Vol 73 (05) ◽  
pp. 798-804 ◽  
Author(s):  
Inger Schousboe ◽  
Margit Søe Rasmussen
Keyword(s):  
Lupus Erythematosus ◽  
Lupus Anticoagulant ◽  
Response Curve ◽  
Inhibitory Effect ◽  
Factor Xii ◽  
High Antibody ◽  
Contact Activation ◽  
Maximal Inhibition ◽  
Lupus Anticoagulants ◽  
Glycoprotein I

SummaryLupus anticoagulants are a group of antibodies commonly found in patients with autoimmune diseases such as systemic lupus erythematosus. Lupus anticoagulants inhibit phospholipid dependent coagulation and may bind to negatively charged phospholipids. Recent studies have suggested an association between anti-β2-glycoprotein I and a lupus anticoagulant, whose activity is frequently dependent on the presence of β2-glycoprotein I. Based on these observations, the effect of anti-β2-glycoprotein I on the autoactivation of factor XII in plasma was investigated. Autoactivation initiated by the presence of negatively charged phospholipids, but not by sulfatide, was strongly inhibited by immunoaffinity purified anti-β2-glycoprotein I. The dose-response curve of anti-β2-gly coprotein I was identical with that of a precipitating antibody, showing no inhibition at low and high antibody dilutions and maximal inhibition at an intermediate dilution. At high antibody concentrations, an increased rate of factor Xlla activation was observed. This increase was of the same magnitude as the decreased rate observed in plasma supplemented with the same amount of β2-glycoprotein I as in the plasma itself. This confirms the inhibitory effect of β2-GP-I on the contact activation and shows that inhibition is effective on the autoactivation of factor XII in plasma. The inhibitory action of β2-glycoprotein I was independent of the inhibition caused by the anti- β2-glycoprotein I/β2-glycoprotein I complex suggesting a synchronized inhibition of factor XII autoactivation by β2-glycoprotein I and anti-β2-gly coprotein I. The inhibition caused by the antibody is suggested to be caused by a reduced availability of negatively charged phospholipids due to the binding of the anti-β2- GP-I/β2-GP-I complex. This complex may be a lupus anticoagulant.

The Diagnosis of Lupus Anticoagulants by the Activated Partial Thromboplastin Time - The Central Role of Phosphatidyl Serine

1984 ◽  
Vol 52 (02) ◽  
pp. 172-175 ◽  
Author(s):  
P R Kelsey ◽  
K J Stevenson ◽  
L Poller
Keyword(s):  
Screening Method ◽  
Coagulation Factors ◽  
Phosphatidyl Serine ◽  
Test System ◽  
Specific Factor ◽  
Marginal Effect ◽  
Constant Composition ◽  
Lupus Anticoagulants ◽  
Different Types

SummaryLiposomes of pure phospholipids were used in a modified APTT test system and the role of phosphatidyl serine (PS) in determining the sensitivity of the test system to the presence of lupus anticoagulants was assessed. Six consecutive patients with lupus anticoagulants and seven haemophiliacs with anticoagulants directed at specific coagulation factors, were studied. Increasing the concentration of phospholipid in the test system markedly reduced the sensitivity to lupus anticoagulants but had marginal effect on the specific factor inhibitors. The same effect was achieved when the content of PS alone was increased in a vehicle liposome of constant composition.The results suggest that the lupus anticoagulants can best be detected by a screening method using an APTT test with a reagent of low PS content. The use of a reagent rich in PS will largely abolish the lupus anticoagulant’s effect on the APTT. An approach using the two different types of reagent may facilitate differentiation of lupus inhibitors from other types of anticoagulant.

A GENERAL MECHANISM FOR LUPUS ANTICOAGULANTS

1987 ◽  
Author(s):  
V Pengo ◽  
M J Heine ◽  
P Thiagarajan ◽  
s s Shapiro
Keyword(s):  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Protein A ◽  
Coagulation Factors ◽  
Phosphatidyl Serine ◽  
General Mechanism ◽  
Factor X ◽  
Lupus Anticoagulants ◽  
Calcium Dependent ◽  
Anionic Phospholipids

Although- a number of observations have implied that lupus anticoagulants have immunologic specificity towards anionic. phospholipids, thereby prolonging phospholipid-dependent coagulation tests, this assumption has been directly demonstrated in only one patient with a monoclonal IgM paraprotein. We have tested the generality of this hypothesis directly by isolating five IgG lupus anticoagulants from patients with lupus-like syndromes and/or thrombosis. IgG lupus anticoagulant fractions were isolated free of other plasma proteins and free of contaminating phospholipid by adsorption to and elution from cardiolipin-cholesterol-dicetylphosphate liposomes , followed by chromatography on protein A-Sepharose. Cardiolipin liposomes, but not phosphatidylcholine liposomes, were capable of removing all, or nearly all, lupus anticoagulant activity from patient plasma. Anticardiolipin and lupus anticoagulant activity were both present in acidic fractions on isoelectric focusing. F(ab’)2 fragments retained lupus anti coagulant activity and bound to cardiolipin in an ELISA assay. The affinity-purified IgG preparations reacted with cardiolipin, phosphatidyl serine , phosphatidylinositol and phosphatidic acid, but not with phosphatidylcholine or phosphatidyl ethanol amine, and inhibited calcium-dependent binding of prothrombin and of factor X to phosphatidy1serine-coated surfaces. These data demonstrate a general mechanism for the action of lupus anticoagulants: antibodies that have immunologic specificity towards anionic phospholipids, thereby blocking the calcium-mediated binding of vitamin K-dependent coagulation factors to coagulation-active phospholipid surfaces.

dRVVT Is more Sensitive than KCT or TTI for Detecting Lupus Anticoagulant Activity of Anti-β2-glycoprotein I Autoantibodies

1999 ◽  
Vol 81 (02) ◽  
pp. 256-258 ◽  
Author(s):  
A. Biasiolo ◽  
P. Rampazzo ◽  
T. Brocco ◽  
V. Pengo
Keyword(s):  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Test System ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Tissue Thromboplastin ◽  
The Mean ◽  
Kaolin Clotting Time ◽  
Antibody Preparations

SummaryAnti-β2-glycoprotein I (β2-GPI) antibodies behave as classical Lupus Anticoagulants (LA), as they inhibit phospholipid-dependent coagulation reactions and their activity disappears in the presence of excess exogenous phospholipids (PLs). We have recently shown that a certain amount of PLs in the dilute Russell Viper Venom Time (dRVVT) test system is required to express LA activity of anti β2-GPI antibodies. We have now extended this observation to two other tests, i.e., Kaolin Clotting Time (KCT) in which PLs are not added, and Tissue Thromboplastin Inhibition test (TTI) in which PLs are extremely diluted. In fact, affinity-purified antibody preparations from 5 patients with antiphospholipid syndrome did not express or only weakly expressed anticoagulant activity in both tests; the mean ratios of coagulation times obtained with purified antibodies and that of control buffer were 1.11 and 1.0 for KCT and TTI, respectively. On the contrary, the mean ratios in dRVVT were 1.31 and 1.49 at a PLs dilution of 1:8 and 1:64, respectively. Therefore, the presence of LA activity due to autoantibodies to β2-GPI is characterized by a positive dRVVT and negative or only weakly positive KCT and TTI.

Antiphospholipid Syndrome: Diagnostic Aspects of Lupus Anticoagulants

2001 ◽  
Vol 86 (07) ◽  
pp. 83-91 ◽  
Author(s):  
J. Arnout
Keyword(s):  
Monoclonal Antibodies ◽  
Antiphospholipid Syndrome ◽  
Autoimmune Disorder ◽  
Coagulation Factors ◽  
Laboratory Diagnosis ◽  
Anticardiolipin Antibodies ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Antigen Antibody

SummaryAntiphospholipid syndrome (APS) is an autoimmune disorder in which antiphospholipid antibodies (aPL) are thought to be involved in the development of venous and/or arterial thrombosis. APL found in this syndrome are antibodies directed against a variety of phospholipid (PL) binding-proteins of which β2-glycoprotein I (β2GPI) and prothrombin are considered to be the major antigens. Some of these antibodies prolong PL-dependent clotting reactions and are termed lupus anticoagulants (LA). Autoimmune aPL which bind through β2GPI to cardiolipin are called anticardiolipin antibodies (aCL). Clinical studies indicate that LA is a stronger risk factor for thrombosis than aCL. The production of monoclonal antibodies against β2GPI and prothrombin has enabled us to understand the mechanism by which LA prolong coagulation in vitro. LA form bivalent antigen-antibody complexes with increased affinity for PL which compete with coagulation factors for the same catalytic surface. These LA positive monoclonal antibodies may be helpful in further improving the laboratory diagnosis of LA.

Quantification of Lupus Anticoagulants in Clinical Samples Using Anti- β2GP1 and Anti-Prothrombin Monoclonal Antibodies

2001 ◽  
Vol 86 (08) ◽  
pp. 584-589 ◽  
Author(s):  
A. Le Querrec ◽  
J. Arnout ◽  
D. Arnoux ◽  
J. Y. Borg ◽  
C. Caron ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Lupus Anticoagulant ◽  
Solid Phase ◽  
Clinical Samples ◽  
Lupus Anticoagulants ◽  
Asymptomatic Patients ◽  
Solid Phase Immunoassay ◽  
Dependent Activity ◽  
Variable Contribution ◽  
Suitable Standard

SummaryQuantification of lupus anticoagulant (LA) in clinical samples is hampered by the lack of a suitable standard of activity. We evaluated the use of mAbs displaying LA activity for this purpose. As most patient samples contain both β2Glycoprotein I (β2GP1) and prothrombin dependent LA, a combination of two mAbs, one of each specificity, was added to normal plasma in a concentration from 0 to 60 g/ml. Eight assay systems using different reagents and instruments were used. The calibration curves were linear for all but one, with marked differences between the responsiveness to each mAb. A panel of plasmas from 69 patients with persistent LA diagnosed using the SSCISTH criteria was tested. An antiphospholipid syndrome (APS) was present in 40, whereas 29 were asymptomatic. LA activities of individual plasmas varied between assays (p <10–4), but homogeneous subgroups were identified. In a majority of samples, LA activity displayed a prothrombin-dependent profile, with a variable contribution of β2GP1-dependent activity. The latter was associated to β2GP1 antibodies detected by solid-phase immunoassay. By using 3 dilute Russell viper venom time assays, higher LA titers were found in APS, compared to asymptomatic patients (p <0.05).

The Activated Seven Lupus Anticoagulant Assay Detects Clinically Significant Antibodies

2008 ◽  
Vol 14 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Gary W. Moore ◽  
Savita Rangarajan ◽  
Geoffrey F. Savidge
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
Anticardiolipin Antibodies ◽  
Activated Partial Thromboplastin Time ◽  
Systemic Lupus ◽  
Lupus Anticoagulants ◽  
Russell’S Viper ◽  
Clinically Significant

Lupus anticoagulants are a heterogeneous group of autoantibodies detected by their effects on phospholipid-dependent coagulation assays. Persistent lupus anticoagulants are associated with thrombotic disease, but not all are clinically significant. Antibody heterogeneity and reagent and test variability dictate that at least 2 tests, of different types, should be used to screen lupus anticoagulants. The objective of this study was to investigate whether the activated seven lupus anticoagulant assay detects clinically significant antibodies. Eighty-two patients with antiphospholipid syndrome (APS) and 32 with systemic lupus erythematosus + positive for activated seven lupus anticoagulant and who were without thrombosis, who were positive by activated seven lupus anticoagulant assay, were investigated for lupus anticoagulants by dilute Russell's viper venom time, dilute activated partial thromboplastin time, and Taipan snake venom time, and for anticardiolipin antibodies. Fifty-seven of the APS patients were positive for lupus anticoagulants in multiple assays, 25 in activated seven lupus anticoagulant alone. Fourteen of the latter group were previously positive in other antiphospholipid antibodies assays, and 11 had only been positive for lupus anticoagulants by activated seven lupus anticoagulant. Twenty-eight had elevated anticardiolipin antibodies, 6 of whom were from the group that was positive in activated seven lupus anticoagulant only. Eight of the systemic lupus erythematosus + lupus anticoagulants (without thrombosis) patients were positive for lupus anticoagulant by activated seven lupus anticoagulant alone and had only been positive in activated seven lupus anticoagulant previously, and none had elevated anticardiolipin antibodies. The remaining 24 patients were lupus-anticoagulant positive in multiple assays, and 9 had elevated anticardiolipin antibodies. Dilute Russell's viper venom time and Dilute activated partial thromboplastin time are widely used to detect lupus anticoagulants and are considered to detect clinically significant antibodies. Activated seven lupus anticoagulant detected antibodies in APS patients who were positive by these assays and also lupus anticoagulants undetectable by the dilute Russell's viper venom time/dilute activated partial thromboplastin time reagents used, demonstrating its utility as a first-line or second-line assay.

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