Lupus Anticoagulants and Thrombosis: Clinical Association of Different Coagulation and Immunologic Tests

2000 ◽  
Vol 84 (12) ◽  
pp. 1012-1016 ◽  
Author(s):  
Jeffrey Dlott ◽  
Francesca Norbis ◽  
Luisa Ruggeri ◽  
Linda Cler ◽  
Douglas Triplett ◽  
...  
Keyword(s):  
At Risk ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Colloidal Silica ◽  
Anticardiolipin Antibodies ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Patients At Risk ◽  
Kaolin Clotting Time

SummaryThe dilute Russell’s viper venom time (dRVVT) and the kaolin clotting time (KCT) are two among the most commonly used coagulation tests for the detection of lupus anticoagulants. The dRVVT seems superior to the KCT in identifying LA-positive patients at risk of thrombosis. However, this relationship is greatly influenced by both the source of reagents and the instrumentation employed to carry out the assays. Therefore, 4 dRVVTs (“home-made” dRVVT, DVV test, Bioclot LA, LA Screen), and one KCT (Kaoclot) were performed in two centers and compared for their retrospective correlation with the thrombotic complications of 72 patients with a previously established diagnosis of lupus anticoagulants. Two other assays (“home-made” KCT, and Colloidal Silica Clotting Time, CSCT) were performed in one of the two centers, and compared with Kaoclot for their clinical correlations in the same population of patients, 44 of whom (61%) had suffered from arterial and/or venous thrombosis. A rather good degree of inter-laboratory and inter-assay correlations of the different tests was found. However, a statistically significant association with thrombosis was found only with the coagulation profile generated using the “homemade” dRVVT. When the commercially available dRVVTs were used, none of the coagulation profiles remained associated with thrombosis. When the assays were analyzed separately, the association with thrombosis was statistically significant for LA screen (p = 0.0019), DVV test (p = 0.0043), and Bioclot (p = 0.0255), and of borderline significance for the “home-made” dRVVT (p = 0.0503) in one center. This last assay was also significantly associated with thrombosis in the other center (p = 0.0139). When venous and arterial thrombosis were considered separately, DVV test was statistically associated with venous thrombosis in both centers (p = 0.0076 and p = 0.0187, respectively), and LA screen in one center (p = 0.0303). No dRVVT was found to correlate with arterial thrombosis. Kaoclot, Colloidal Silica Clotting Time, and the “home-made” KCT did not correlate with thrombosis. The prevalence of IgG and/or IgM antibodies to cardiolipin, β2-glycoprotein I and prothrombin were 74%, 86% and 85%, respectively. Increased titers of IgG anticardiolipin antibodies were associated with arterial thrombosis (p = 0.0375), whereas IgM anti-β2-glycoprotein I antibodies were associated with venous thrombosis (p = 0.0433). In conclusion, these retrospective data support the notion that the dRVVT, rather than other coagulation or ELISA tests, are able to identify lupus anticoagulant-positive patients at risk of thrombosis. This property appears common to several commercially available dRVVT kits, making this type of assay the ideal target of future efforts of laboratory standardization.

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.

Phospholipid inhibitors

2011 ◽  
Vol 31 (04) ◽  
pp. 243-250 ◽  
Author(s):  
M. Galli
Keyword(s):  
Venous Thrombosis ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Anticardiolipin Antibodies ◽  
Low Molecular Weight ◽  
Obstetrical Complications ◽  
Glycoprotein I ◽  
Long Duration ◽  
Activity Dependent ◽  
Cerebral Arterial Thrombosis

SummaryThe antiphospholipid syndrome (APS) is defined by the association of arterial and/or venous thrombosis and/or pregnancy complications with the presence of at least one among the main antiphospholipid antibodies (aPL) (i. e., Lupus anticoagulants, LA, IgG and/ or IgM anticardiolipin antibodies, aCL, IgG and/or IgM antiβ2-glycoprotein I antibodies, aβ2-GPI). Several clinical studies have consistently reported that LA is a stronger risk factor for both arterial and venous thrombosis compared to aCL and aβ2-GPI. In particular, LA activity dependent on the first domain of β2-GPI and triple aPL positivity are associated with the risk of thrombosis and obstetrical complications.Asymptomatic aPL-positive subjects do not require primary thromboprophylaxis. Venous thromboembolism is the most common initial clinical manifestation of APS. To prevent its recurrence indefinite anticoagulation is recommended. Long duration treatment with warfarin or aspirin is used after a first cerebral arterial thrombosis. Low molecular weight heparin (LMWH) with or without aspirin is recommended to reduce the rate of obstetrical complications of APS pregnant women.

The Coinicidence of Venous and Arterial Thrombosis in Patients with Antiphospholipid Syndrome - Correlation with Laboratory Findings.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4045-4045
Author(s):  
Wolfgang A. Miesbach ◽  
Robert Hudeck ◽  
Martina Boehm ◽  
Inge Scharrer
Keyword(s):  
Venous Thrombosis ◽  
Antiphospholipid Syndrome ◽  
Arterial Thrombosis ◽  
Clinical Manifestations ◽  
Anticardiolipin Antibodies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Range ◽  
Laboratory Findings ◽  
Lupus Anticoagulants ◽  
Vein Thrombosis

Abstract The antiphospholipid syndrome (APS) is one of the most common acquired causes of thrombosis on the venous or arterial site. The initial type of the thrombosis appears to be the most likely type of event to recur. In general, APS patients present more common venous thrombosis, especially deep vein thrombosis of the legs. Arterial thromboses are less common and mostly manifest with ischemia or infarction. It is not clear whether a combination of phospholipid antibodies or the additional presence of lupus anticoagulants in patients with anticardiolipin antibodies increase the risk of manifestation of APS. Methods: We investigated retrospectively 300 patients with elevated aCL antibodies. IgG and IgM aCL antibodies were tested by enzyme-linked immunosorbent assay (ELISA). LA were tested by more than 2 different methods according to the proposed criteria of the SSC of the ISTH. Results: Of these patients, 61 % suffered from manifestations of APS, 35 % from venous and 28 % from arterial thrombosis, 7 % of the patients had abortions. In 39 % no thromboembolic disease was found. The coincidence of venous and arterial thrombosis was found in 25/300 (8 %) of the patients. An increased titer of IgG aCL was found in 135 of 300 patients (45 %, median 49 GPL-U/ml, normal range: - 11,3 GPL-U/ml), and an increased titer of IgM aCL in 260 patients (87 %, median 13 MPL-U/ml, normal range: 5,6 MPL-U/ml). Lupus anticoagulants were additionally detected in 130/300 patients (43 %). The rate of clinical manifestations did not differ between LA-positive patients (78 of 130 patients, 60 %) and LA-negative patients (105 of 170, 62 %) patients with elevated aCL antibodies. Regarding the patients with the coincidence of venous and arterial thrombosis, we found a significantly higher rate of positive lupus anticoagulants than in the patients with APS manifestation of one site only (17/25 vs. 113/275, p < 0.05, OR 3.04; 95 % CI 1.31 – 7.06). An elevation of IgG-aCL titres were more frequently found, too. Table 1: Characteristics of the patients with a coincidence of venous and arterial thrombosis compared to patients with thrombosis of one site only Conclusion: The additional presence of lupus anticoagulants in patients with anticardiolipin antibodies identifies a group of patients with high risk of recurrent manifestations of the antiphospholipid syndrome. Particularly the risk of manifestation of both, arterial and venous thrombosis in these patients should be early recognized to initiate a careful follow-up and antithrombotic therapy in these patients. Venous and Arterial Thrombosis Thrombosis of One Site No APS Manifestation n 25/300 (8 %) 157/300 (59 %) 118/300 (39 %) Age (yrs) median 48.5 50 46 Sex (F/M) 17/8 (2.1) 62/157 (2.1) 51/118 (2.3) LA 17/25 (68 %) 62/157 (39 %) 51/118 (43 %) IgG-aCL 15/25 (60 %) 73/157 (46 %) 47/118 (40 %) median titre 108 GPL 87 GPL 37 GPL IgM-aCL 24/25 (96 %) 129/157 (82 %) 104/118 (88 %) median titre 13 MPL 14 MPL 14 MPL

Lupus Anticoagulant is the Strongest Risk Factor for both Venous and Arterial Thrombosis in Patients with Systemic Lupus Erythematosus

1996 ◽  
Vol 76 (06) ◽  
pp. 0916-0924 ◽  
Author(s):  
Daniëlle A Horbach ◽  
Erica V Oort ◽  
Richard C J M Donders ◽  
Ronald H W M Derksen ◽  
Philip G de Groot
Keyword(s):  
At Risk ◽  
Risk Factor ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Lupus Anticoagulant ◽  
Plasma Proteins ◽  
Patients At Risk ◽  
History Of ◽  
Thrombotic Complications ◽  
Risk For Thrombosis

SummaryAntiphospholipid antibodies (aPL) characterize patients at risk for both arterial and venous thrombotic complications. Recently it has been recognized that the presence of plasma proteins such as β2-glycoprotein I (β2GPI) and prothrombin are essential for the binding of aPL to phospholipids and that these proteins are probably the real target of aPL. The discovery of these new antigens for aPL introduces the possibility of new assays to detect the presence of aPL. However, it is not known whether these assays improve the identification of patients at risk for thrombosis.In this retrospective study we compared the value of the classic assays LAC (lupus anticoagulant) and ACA (anticardiolipin antibodies) to detect aPL associated with thrombotic complications, with new assays which are based on the binding of aPL to the plasma proteins prothrombin and P2GPI. To do so, we have used these assays in a group of 175 SLE patients and correlated the positivity of the different assays with the presence of a history of venous and arterial thrombosis. Control groups were patients without SLE but with LAC and/or ACA and thrombosis (n = 23), patients with thrombosis without LAC and ACA (n = 40) and 42 healthy controls.In the univariate analysis, in which no distinction has been made between high and low antibody levels, we confirmed LAC and ACA to be related to both arterial and venous thrombosis. Anti-β2GPI- and anti-prothrombin-antibodies, both IgG and IgM correlate with venous thrombosis and anti-β2GPI-IgM with arterial thrombosis. Multivariate analysis showed that LAC is the strongest risk factor (OR 9.77; 95% CI 1.74-31.15) for arterial thrombosis. None of the other factors is a significant additional risk factor. For venous thrombosis LAC is the strongest risk factor (OR 6.55; 95% Cl 2.36-18.17), but ACA-IgM above 20 MPL units also appeared to be a significant (p = 0.0159) risk factor (OR 3.90; 95% Cl 1.29-11.80). Furthermore, the presence of anti-β2GPI- and/or anti-prothrombin-antibodies in LAC positive patients (n = 60) does not increase the risk for thrombosis.The results showed that (i) the LAC assay correlates best with a history of both arterial and venous thrombosis and (ii) neither the anti-P2GPI ELISA nor the anti-prothrombin ELISA gives additional information for a thrombotic risk in SLE patients.

Anti-β2-Glycoprotein I and Anti-Prothrombin Antibodies in Antiphospholipid-Negative Patients with Thrombosis

2002 ◽  
Vol 88 (11) ◽  
pp. 729-732 ◽  
Author(s):  
Sara Previtali ◽  
Tiziano Barbui ◽  
Monica Galli
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Lupus Erythematosus ◽  
Normal Subjects ◽  
Anticardiolipin Antibodies ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Significant Relationships ◽  
Antiprothrombin Antibodies ◽  
Independent Risk Factors

SummaryWe performed a case-control study to assess whether anti-β2-glycoprotein I and anti-prothrombin antibodies are independent risk factors of thrombosis. Cases were 79 patients with arterial and/or venous thrombosis without lupus anticoagulants, anticardiolipin antibodies and systemic lupus erythematosus; controls were 85 normal subjects. The prevalences and titers of IgG and IgM anti-β2-glycoprotein I and antiprothrombin antibodies were similar in both groups. Cases were analyzed with respect to the arterial or venous type of thrombosis and to the presence of congenital or acquired risk factors for thrombosis: no statistically significant relationships with the presence of anti-β2glycoprotein I and anti-prothrombin antibodies were found. Our data indicate that anti- β2-glycoprotein I and anti-prothrombin antibodies are not risk factors for thrombosis independent of lupus anticoagulants and anticardiolipin antibodies. Their measurement, therefore, is not warranted in the laboratory screening of patients with arterial and/or venous thrombosis.

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.

Silent Venous Thrombosis Revealed by Impedance and 125I-Fibrinogen

1975 ◽  
Author(s):  
M. Hume
Keyword(s):  
At Risk ◽  
Pulmonary Embolism ◽  
Venous Thrombosis ◽  
Clinical Significance ◽  
Total Hip Replacement ◽  
Hip Replacement ◽  
Clinical Evidence ◽  
Impedance Plethysmography ◽  
Patients At Risk ◽  
Lung Scan

100 post-operative subjects were observed following total hip replacement using 125I-fibrinogen (125I-Fg) and impedance plethysmography (IPG) with thigh cuff. Phlebo-grams were obtained if these tests indicated venous thrombosis. Also, lung scan was obtained if clinical evidence of pulmonary embolism developed. Sustained significant isotope localization occurred in 40. 32 of these had abnormal IPG. Four patients had minor pulmonary embolism, which was associated with abnormality of either 125I-Fg or IPG. All major obstructive venous thrombosis and all moderately extensive thrombosis was associated with abnormal IPG. Only minute thrombi were not correctly classified by IPG. The following conclusions are supported by this experience. 1) If prospectively applied in patients at risk, the combination of both techniques (125I-Fg, IPG) is capable of detecting all silent venous thrombosis even minute thrombi of negligible significance. 2) IPG is capable of detecting all major obstructive and all moderately extensive thrombi, that is, all thrombosis of clinical significance arising in the leg. 3) Minute thrombi will not be detected by IPG alone and small emboli resulting from detachment of such minute thrombi would be unheralded unless monitoring includes 125I-Fg.

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.

scholarly journals Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis

2010 ◽  
Vol 128 (5) ◽  
pp. 263-267 ◽  
Author(s):  
Mahendra Narain Mishra ◽  
Varinder Singh Bedi
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Quantitative Estimation ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Factor V ◽  
Cross Sectional ◽  
C Protein ◽  
Lupus Anticoagulants ◽  
Significant Difference

CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56%) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9% each), followed by low protein S (16.6%). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.

Mechanism of action of β2-glycoprotein I-dependent lupus anticoagulants

Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 23-28 ◽  
Author(s):  
J Amout ◽  
J Vermylen
Keyword(s):  
Mechanism Of Action ◽  
Molecular Basis ◽  
Current Knowledge ◽  
Indirect Evidence ◽  
Integrated Model ◽  
Anticardiolipin Antibodies ◽  
Pathogenic Role ◽  
Lupus Anticoagulants ◽  
Glycoprotein I

There is accumulating evidence showing that lupus anticoagulants (LA) are more strongly associated with thrombosis than anticardiolipin antibodies. In addition, indirect evidence has been presented indicating that β2GPI-dependent LA are more strongly associated with thrombosis than prothrombin-dependent LA. From this, one may assume that anti-β2GPl antibodies with LA activity are more pathogenic than anti-β2GPI antibodies without LA activity. Therefore, it is of the utmost importance to understand the molecular basis on which some anti-β2GPI antibodies behave as LA. In this presentation, the current knowledge on the interaction of β2GPI with phospholipids and with anti-β2GPI antibodies is reviewed and an integrated model for the anti-β2GPI - dependent LA activity is proposed with implications for a pathogenic role of these particular antibodies.

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