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.

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.

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.

COMPARISION OF THE DETECTION OF LUPUS ANTICOAGULANTS USING THREE DIFFERENT METHODS AND THE PRESENCE OF ANTI-CARDIOLIPIN ANTIBODIES

1987 ◽  
Author(s):  
A Criel ◽  
B Gilbert ◽  
A Van Hoof ◽  
M Hidajat ◽  
A Louwagie
Keyword(s):  
Elisa Test ◽  
Activated Partial Thromboplastin Time ◽  
Detection Methods ◽  
Recurrent Abortion ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Cardiolipin Antibodies ◽  
Tissue Thromboplastin ◽  
Kaolin Clotting Time

Lupus anticoagulant (LAC) is an antibody directed against phospholipids which prolongs in vitro clotting assays. Several detection methods have been described; however all give some different results. Recently ELISA and RIA assays have been developed which detect IgG and IgM anti-cardiolipin antibodies. The aim of our study was to compare three different LAC tests with an ELISA anti-cardiolipin test. The tests used were : kaolin clotting time (KCT or Exnertest), tissue thromboplastin inhibition test (TTI or Schleider test), activated partial thromboplastin time using a 50, 100, 200 fold dilution of the phospholipid preparation (APTT dilution test), and an IgG and IgM anti-cardiolipin ELISA test. 114 samples of patients suffering from diseases known to be accompanied with LAC antibodies (auto-immune diseases, recurrent abortion, thromboembolism, etc.) were studied. Positivity with one of the tests was found in 45 patients (39%). Patients with the diagnosis of SLE or otherimmune diseases showed the highest positivity (56%) whereas those with thromboembolism, recurrent abortion etc. were only positive in 27%.Among these 45 positive patients the TTI was positive in 41 cases (91 %);however in 10 cases (24 %) this was the only positivity found. The KCT test and the APTT dilution test were both positive in 18 cases (40 %). Anti-cardiolipin antibodies were found in 21 patients (47 %): IgG only in 12 (27 %), IgM only in 5 (11 %), both IgG and IgM in 2 (4 %); in 19 of these 21 patientsthe TTI was also positive.In our study the TTI test seems to be the most sensitive test but possibly also the test with the highest aspecific positivities. IgG and IgM anti-cardiolipin antibodies were less frequently found than expected.

scholarly journals Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit

Blood ◽  
1990 ◽  
Vol 76 (8) ◽  
pp. 1538-1545 ◽  
Author(s):  
KC Day ◽  
LC Hoffman ◽  
MO Palmier ◽  
KK Kretzmer ◽  
MD Huang ◽  
...  
Keyword(s):  
Body Weight ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Rabbit Model ◽  
Activated Partial Thromboplastin Time ◽  
High Dose ◽  
Intravascular Coagulation ◽  
Coagulation Inhibitor ◽  
Tissue Thromboplastin ◽  
Induced Radioactivity

Lipoprotein-associated coagulation inhibitor produces feed-back inhibition of tissue factor (tissue thromboplastin)-induced coagulation in the presence of factor Xa Recombinant lipoprotein-associated coagulation inhibitor (rLACI) was tested for its ability to modify thromboplastin-induced intravascular coagulation in a rabbit model that allows monitoring of iodine-125 fibrin accumulation/disappearance in the lung and sampling of blood for the measurement of coagulation parameters. Infusion of thromboplastin into the rabbit caused a rapid increase of radioactivity over the lungs, possibly due to the accumulation of 125I fibrin in the lungs, followed by a rapid decline of radioactivity, suggestive of removal of fibrin from the lungs. Thromboplastin also caused a rapid decrease of systemic fibrinogen that was accompanied by a lengthening of the activated partial thromboplastin time and prothrombin time. The effect of coinfusion of rLACI with thromboplastin or bolus injection of rLACI before thromboplastin infusion was studied. At a high dose of rLACI (800 micrograms/kg body weight), the thromboplastin-induced radioactivity increase in the lungs and the systemic fibrinogen decrease were completely suppressed. The activated partial thromboplastin time and prothrombin time of the plasma samples lengthened, possibly due to the presence of thromboplastin in circulation. The thromboplastin-induced radioactivity increase over the lungs was not completely suppressed by lower doses of rLACI (135 to 270 micrograms/kg body weight), but these doses of rLACI prevented systemic fibrinogen decrease. At a bolus dose of 23 micrograms/kg body weight, rLACI provided 50% protection of the fibrinogen consumption (fibrinogen decreased to 82% compared with 65% in rabbits treated with thromboplastin alone). These results show that rLACI is effective in the inhibition of thromboplastin-induced coagulation in vivo.

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.

The Dilute Phospholipid APTT: A Sensitive Assay for Verification of Lupus Anticoagulants

1985 ◽  
Vol 54 (03) ◽  
pp. 709-712 ◽  
Author(s):  
Barbara M Alving ◽  
Phillip E Baldwin ◽  
Roberta L Richards ◽  
Beverly J Jackson
Keyword(s):  
Regression Analysis ◽  
Partial Thromboplastin Time ◽  
Coagulation Factor ◽  
Activated Partial Thromboplastin Time ◽  
Negative Slope ◽  
Sensitive Assay ◽  
Lupus Anticoagulants ◽  
Normal Plasma ◽  
The Mean ◽  
Sensitive Method

SummaryA simple sensitive method for verification of lupus anticoagulants utilizing dilution of phospholipid in the activated partial thromboplastin time (APTT) system is described. Patient plasma, mixed with an equal volume of normal plasma, is activated with micronized silica. To this mixture are added different dilutions of Thrombofax® and then calcium chloride. Clotting times are plotted linearly against the logarithm of the phospholipid dilutions and slopes are calculated by regression analysis. In this assay the mean negative slope of 19 plasmas that contained antiphospholipid activity was five times greater than those of normal plasma or those obtained from patients having single or multiple coagulation factor deficiencies such as those induced by warfarin. The assay can be modified to test heparinized plasmas. Thus, it is a sensitive means by which to verify the presence of lupus anticoagulants in patients who have congenital or acquired factor deficiencies or who are receiving anticoagulant therapy.

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