Evaluation of Recently Described Tests for Detection of the Lupus Anticoagulant

1994 ◽  
Vol 72 (05) ◽  
pp. 728-733 ◽  
Author(s):  
Ricardo R Forastiero ◽  
Graciela S Cerrato ◽  
Luis O Carreras
Keyword(s):  
Human Placenta ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
High Sensitivity ◽  
Activated Partial Thromboplastin Time ◽  
Lupus Anticoagulants ◽  
Coagulation Tests ◽  
Prolonged Aptt ◽  
Tissue Thromboplastin ◽  
Standard Tests

SummaryIt is known that lupus anticoagulants (LA) are antibodies which interfere with phospholipid-dependent coagulation tests, but due to the heterogeneity of LA and the differences in sensitivity of reagents and tests, the diagnosis of LA remains difficult.Recently, Triplett et al. (26) have proposed a new test based on two venoms, Textarin (T) and Ecarin (E), that activate prothrombin but differ in their phospholipid requirements. By testing this new assay we have evaluated 36 patient plasmas containing LA according to standard tests (activated partial thromboplastin time, dilute Russell viper venom time and platelet neutralization procedure) and our results confirm a high sensitivity for LA of the T/E test.In addition, we observed a greater sensitivity of the tissue thromboplastin inhibition test using a recombinant thromboplastin instead of a human placenta thromboplastin.Our study also showed that the T/E test seems to be a useful assay in confirming the diagnosis of LA in patients with an unexplained prolonged APTT.

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.

How to Optimize Activated Partial Thromboplastin Time (APTT) Testing: Solutions to Establishing and Verifying Normal Reference Intervals and Assessing APTT Reagents for Sensitivity to Heparin, Lupus Anticoagulant, and Clotting Factors

2019 ◽  
Vol 45 (01) ◽  
pp. 022-035 ◽  
Author(s):  
Geoffrey Kershaw ◽  
Soma Mohammed ◽  
Giuseppe Lippi ◽  
Emmanuel Favaloro
Keyword(s):  
Molecular Weight ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
High Sensitivity ◽  
Activated Partial Thromboplastin Time ◽  
Factor Xii ◽  
Reference Ranges ◽  
Clotting Factors ◽  
Hospital System ◽  
Normal Reference

AbstractThe activated partial thromboplastin time (APTT) assay is a very common coagulation test, used for several reasons. The test is conventionally used for assessing the contact factor (intrinsic) pathway of blood coagulation, and thus for screening deficiencies in this pathway, most typically factors VIII, IX, and XI. The APTT is also sensitive to contact factor deficiencies, including factor XII, prekallikrein, and high-molecular-weight kininogen. The APTT may also be elevated in a variety of conditions, including liver disease, vitamin K deficiency, and disseminated intravascular coagulation. The APTT can also be used for monitoring unfractionated heparin (UFH) therapy, as well as for screening lupus anticoagulant (LA) or for assessing thrombosis risk. Which of these separate uses is important to a given laboratory or clinician depends on the laboratory and the clinical context. For example, UFH sensitivity is important in hospital-based laboratories, where UFH therapy is used, but not in hospital-based laboratories where low-molecular-weight heparin (LMWH) is largely employed or where UFH may be assessed by anti-factor Xa testing, or in private/community laboratories not associated with a hospital system. High sensitivity to (low levels of) factors VIII, IX, and XI is generally preferred, as their deficiencies are clinically significant. Also preferred, but not usually achieved, is low sensitivity to factor XII and other contact factors, as these deficiencies are usually asymptomatic. Nevertheless, a good knowledge of factor sensitivity is usually needed, if only to help explain the reasons for a prolonged APTT in a given patient, or whether factor testing or other investigation is required. A good working knowledge of reagents sensitivity to LA is also advisable, especially when the reagent is used as part of a LA test panel, or else as a “general-purpose screening reagent.” The current report is aimed at providing some guidance around these questions, and is intended as a kind of “how to” guide, that will enable laboratories to assess APTT reagents in regard to their sensitivity to heparin, LA, and clotting factors. The report also provides some advice on generation of normal reference ranges, as well as solutions for troubleshooting prolonged APTTs, when performing factor testing or searching for inhibitors.

Comparison Between a One-Point Dilute Phospholipid APTT and the Dilute Russell Viper Venom Time for Verification of Lupus Anticoagulants

1992 ◽  
Vol 67 (06) ◽  
pp. 672-678 ◽  
Author(s):  
Barbara M Alving ◽  
Charles F Barr ◽  
Lawrence E Johansen ◽  
Douglas B Tang
Keyword(s):  
Partial Thromboplastin Time ◽  
Antiphospholipid Antibodies ◽  
Test System ◽  
Bovine Brain ◽  
Activated Partial Thromboplastin Time ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Normal Plasma ◽  
Prolonged Aptt ◽  
Higher Sensitivity

SummaryIn the present study, the dilute Russell viper venom time (RVVT) and the dilute phospholipid activated partial thromboplastin time (PL-APTT), which are two assays used for the verification of lupus anticoagulants (LA), were modified to increase standardization. The modified assays were then compared with respect to sensitivity and specificity in detecting LA in plasmas from 72 patients with a prolonged APTT. Modifications included utilizing a single dilution of phospholipid that was either bovine brain thromboplastin (Thrombofax) or liposomes comprised of phosphatidylcholine/phosphatidylserine, and expressing the results as a ratio of the clotting times of the mixture of patient and normal plasma/clotting time of normal plasma. In the RWT, the correlation coefficient between assay results for liposomes and Thrombofax was 0.88 and in the PL-APTT, the correlation was 0.68. A positive test for LA was defined as a ratio of ≥1.3 for the PL-APTT with liposomes and ≥1.2 for the PL-APTT with Thrombofax and the RWT with Thrombofax or liposomes. Regardless of the phospholipid source in the test system, the PL-APTT demonstrated higher sensitivity and the RWT showed greater specificity in detecting patient plasmas that contained antiphospholipid antibodies.

scholarly journals Anti-prothrombin antibodies and the lupus anticoagulant

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 512-519 ◽  
Author(s):  
RA Fleck ◽  
SI Rapaport ◽  
LV Rao
Keyword(s):  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Activated Partial Thromboplastin Time ◽  
Lupus Anticoagulants ◽  
Crossed Immunoelectrophoresis ◽  
High Prevalence

Abstract The investigators have evaluated the frequency and manifestations of anti-prothrombin antibodies in patients with the lupus anticoagulant. Thirty-one of 42 patients with lupus anticoagulants associated with a variety of underlying conditions (74%) had evidence on crossed immunoelectrophoresis of anti-prothrombin antibodies. Twenty-four of 25 patients with an activated partial thromboplastin time exceeding 50 seconds and 14 of 15 patients with a prothrombin time exceeding control by more than two seconds had demonstrable anti-prothrombin antibodies. Three of the 31 patients with anti-prothrombin antibodies had essentially no measurable plasma prothrombin, a presumed result of accelerated clearance of prothrombin/prothrombin antibody complexes. Each of these patients had bled abnormally. The remaining patients with anti-prothrombin antibodies had neither substantial hypoprothrombinemia nor hemorrhagic manifestations, which confirms the non-neutralizing property of anti-prothrombin antibodies associated with the lupus anticoagulant. Since lupus anticoagulant immunoglobulins are known to react with phospholipids, the high prevalence of antibodies binding prothrombin led us to test the hypothesis of antibody polyreactivity. Adsorption of three lupus anticoagulant plasmas with insolubilized prothrombin markedly diminished evidence of both prothrombin/prothrombin antibody complexes and anticoagulant activity. Eluates of the insolubilized prothrombin contained IgG that not only bound prothrombin but possessed lupus anticoagulant activity.

scholarly journals The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 869-874 ◽  
Author(s):  
P Thiagarajan ◽  
V Pengo ◽  
SS Shapiro
Keyword(s):  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Inhibition Test ◽  
Specific Method ◽  
Lupus Anticoagulants ◽  
Tissue Thromboplastin

Abstract We describe here a test for lupus anticoagulants based on a modified Russell viper venom time (RVVT), using limiting amounts of phospholipid and venom. We have studied 29 patients with a prolonged dilute RVVT. Five of the 29 had a normal activated partial thromboplastin time and three of 14 tested by the tissue thromboplastin inhibition test were normal. In 17 of 19 patients tested, the dilute RVVT was completely normal when ionophore-treated platelets were substituted for phospholipid; the remaining two patients, both with very long phospholipid-dependent dilute RVVT's, were nearly completely normalized. The dilute RVVT is not prolonged in the presence of antibodies to factors VIII, IX, or XI. Thus, the dilute RVVT appears to be a simple, reproducible, sensitive, and relatively specific method for the detection of lupus anticoagulants.

scholarly journals The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 869-874 ◽  
Author(s):  
P Thiagarajan ◽  
V Pengo ◽  
SS Shapiro
Keyword(s):  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Inhibition Test ◽  
Specific Method ◽  
Lupus Anticoagulants ◽  
Tissue Thromboplastin

We describe here a test for lupus anticoagulants based on a modified Russell viper venom time (RVVT), using limiting amounts of phospholipid and venom. We have studied 29 patients with a prolonged dilute RVVT. Five of the 29 had a normal activated partial thromboplastin time and three of 14 tested by the tissue thromboplastin inhibition test were normal. In 17 of 19 patients tested, the dilute RVVT was completely normal when ionophore-treated platelets were substituted for phospholipid; the remaining two patients, both with very long phospholipid-dependent dilute RVVT's, were nearly completely normalized. The dilute RVVT is not prolonged in the presence of antibodies to factors VIII, IX, or XI. Thus, the dilute RVVT appears to be a simple, reproducible, sensitive, and relatively specific method for the detection of lupus anticoagulants.

Spurious Prolongation of the Activated Partial Thromboplastin Time

1977 ◽  
Vol 38 (04) ◽  
pp. 0900-0908 ◽  
Author(s):  
Robert A. Okpara ◽  
Joann Carabello ◽  
H James Day
Keyword(s):  
Partial Thromboplastin Time ◽  
Laboratory Data ◽  
Activated Partial Thromboplastin Time ◽  
Rate Of Change ◽  
Maximal Rate ◽  
Middle Stage ◽  
Normal Plasma ◽  
Prolonged Aptt ◽  
Tissue Thromboplastin ◽  
Abnormal Tissue

SummaryThe clinical and laboratory data of 8 patients (4 males and 4 females) with circulating anticoagulant were presented. Based on prolonged APTT, failure to correct the APTT with 50 % normal plasma and abnormal tissue thromboplastin inhibition test, the inhibitor was identified as “middle stage” – or the “lupus anticoagulant”. Thrombokinetics showed the maximal rate of change in optical density (VmaxΔOD) of plasma, resulting from clot formation to be significantly less in the plasma of patients with the inhibitor than in normal plasma. This was not completely corrected by mixing the patients’ plasma with 50% normal plasma.

scholarly journals Anti-prothrombin antibodies and the lupus anticoagulant

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 512-519
Author(s):  
RA Fleck ◽  
SI Rapaport ◽  
LV Rao
Keyword(s):  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Activated Partial Thromboplastin Time ◽  
Lupus Anticoagulants ◽  
Crossed Immunoelectrophoresis ◽  
High Prevalence

The investigators have evaluated the frequency and manifestations of anti-prothrombin antibodies in patients with the lupus anticoagulant. Thirty-one of 42 patients with lupus anticoagulants associated with a variety of underlying conditions (74%) had evidence on crossed immunoelectrophoresis of anti-prothrombin antibodies. Twenty-four of 25 patients with an activated partial thromboplastin time exceeding 50 seconds and 14 of 15 patients with a prothrombin time exceeding control by more than two seconds had demonstrable anti-prothrombin antibodies. Three of the 31 patients with anti-prothrombin antibodies had essentially no measurable plasma prothrombin, a presumed result of accelerated clearance of prothrombin/prothrombin antibody complexes. Each of these patients had bled abnormally. The remaining patients with anti-prothrombin antibodies had neither substantial hypoprothrombinemia nor hemorrhagic manifestations, which confirms the non-neutralizing property of anti-prothrombin antibodies associated with the lupus anticoagulant. Since lupus anticoagulant immunoglobulins are known to react with phospholipids, the high prevalence of antibodies binding prothrombin led us to test the hypothesis of antibody polyreactivity. Adsorption of three lupus anticoagulant plasmas with insolubilized prothrombin markedly diminished evidence of both prothrombin/prothrombin antibody complexes and anticoagulant activity. Eluates of the insolubilized prothrombin contained IgG that not only bound prothrombin but possessed lupus anticoagulant activity.

Detection of Lupus-Like Anticoagulants by an Enzyme-Linked Immunosorbent Assay Using a Partial Thromboplastin as Antigen; A Comparative Study

1990 ◽  
Vol 64 (01) ◽  
pp. 026-031 ◽  
Author(s):  
J Arnout ◽  
E Huybrechts ◽  
M Vanrusselt ◽  
C Falcon ◽  
J Vermylen
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Activated Partial Thromboplastin Time ◽  
The Other ◽  
Quantitative Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clotting Time ◽  
Coagulation Tests ◽  
Tissue Thromboplastin ◽  
Kaolin Clotting Time

SummaryClotting assays allow qualitative rather than quantitative detection of the lupus anticoagulant. We have therefore studied the usefulness of an ELISA using a commercial partial thromboplastin, Thrombofax, oS antigen; the results obtained on 146 selected patient plasmas were compared to the results of coagulation tests (kaolin clotting time, tissue thromboplastin inhibition test, activated partial thromboplastin time) and of ELISAs using cardiolipin or phosphatidylserine as antigen. While satisfactory agreement was found within the group of coagulation tests or that of ELISAs, only a moderate agreement was obtained between clotting tests and ELISAs, the best being with the partial thromboplastin ELISA using low plasma dilutions. The study further indicates that ELISA techniques cannot entirely replace coagulation tests for the detection of a lupus anticoagulant, even when a partial thromboplastin is used as antigen. On the other hand, coagulation tests are less sensitive than ELISAs for the detection of antiphospholipid antibodies.

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.

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