The clinical relevance of isolated lupus anticoagulant positivity in patients with thrombotic antiphospholipid syndrome

2020 ◽  
Author(s):  
Dong-mei Yin ◽  
Philip de Groot ◽  
Marisa Ninivaggi ◽  
Katrien M.J. Devreese ◽  
Bas de Laat
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Relevance ◽  
Antiphospholipid Antibodies ◽  
Odds Ratio ◽  
Lupus Anticoagulant ◽  
Solid Phase ◽  
Control Group ◽  
Domain I ◽  
Normal Controls ◽  
Better Than

Background: Patients positive for three types of antiphospholipid antibodies (aPLs) (triple positivity) have been identified at a high risk for thrombotic events. However, the clinical significance of isolated lupus anticoagulant (LAC) positivity is debated. Objectives: To investigate the clinical relevance of isolated LAC. Patients/Methods 456 patients were enrolled in this study; 66 antiphospholipid syndrome patients and 390 control patients. The control group existed of autoimmune patients (n=91), patients with thrombosis but without aPLs (n=127) and normal controls (n=172). The criteria LAC, anti-cardiolipin (anti-CL) and anti-beta2glycoprotein I (anti-β2GPI) IgG and IgM and the non-criteria IgA anti-CL and anti-β2GPI, anti-domain I (anti-DI) of β2GPI IgG and anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG and IgM were detected according to the ISTH guidelines for solid phase assays. Results: 70 patients were positive for LAC, of which 44 were negative for both anti-β2GPI and anti-CL. We found that isolated LAC proved to be strongly associated with vascular thrombosis (Odds ratio (OR) (95% CI) 7.3 (3.3-16.1)), even better than triple positive samples (OR 4.3 (1.6-12.2)). The titers of the anti-PS/PT IgG and IgM were significantly higher in triple positivity samples compared to samples with isolated LAC positivity. The majority of single LAC positives were anti-PS/PT negative. We observed that LAC positivity was weaker in isolated LAC positive patients compared to LAC activity in triple positive patients. Conclusions: Isolated LAC was highly associated with thrombosis. The presence of anti-PS/PT could not explain LAC positivity in isolated LAC. Isolated LAC showed a weaker LAC activity compared to triple positive patients.

The Clinical Relevance of Noncriteria Antiphospholipid Antibodies

2017 ◽  
Vol 44 (05) ◽  
pp. 453-457 ◽  
Author(s):  
Giovanni Sanna ◽  
Maria Bertolaccini
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Relevance ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Clinical Utility ◽  
Diagnostic Value ◽  
Anticardiolipin Antibodies ◽  
Coagulation Cascade ◽  
Glycoprotein I

AbstractWhile lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β2 glycoprotein I (anti-β2GPI) antibodies represent the best available and the most widely used tests in the investigation for antiphospholipid syndrome (APS), evidence gathered in recent years indicates that other antiphospholipid antibodies (aPL) specificities may also play a role in the syndrome. Several autoantibodies have been shown to be complexed with phospholipids other than cardiolipin, or to some domains of β2GPI, or else directed to other proteins of the coagulation cascade, and these have also been proposed to be of relevance to APS, and their diagnostic value and clinical utility are the focus of current research.

Laboratory Evaluation of Antiphospholipid Syndrome

2019 ◽  
Author(s):  
Nahla Heikal ◽  
Thomas B Martins ◽  
Sandra K White ◽  
Rohan Willis ◽  
D Ware Branch ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Odds Ratio ◽  
Lupus Anticoagulant ◽  
Diagnostic Yield ◽  
Optimal Strategies ◽  
Laboratory Evaluation ◽  
Igm Antibodies ◽  
Glycoprotein I ◽  
Domain I ◽  
Prospective Investigation

Abstract Objectives Anti-β2 glycoprotein I domain I (anti-domain I) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are present in patients with antiphospholipid syndrome (APS); however, their use in evaluation remains unclear. Methods Diagnostic attributes of lupus anticoagulant (LAC), anti-domain I IgG, anti-cardiolipin, anti-β2 glycoprotein I (anti-β2GPI), and aPS/PT IgG and IgM antibodies were assessed in 216 patients evaluated for APS. Results LAC had the best odds ratio (OR, 14.2) while that for anti-domain 1 IgG was comparable to anti-β2GPI IgG (OR, 8.3 vs 9.4) but higher than all others. Significant correlations were observed for thrombosis (P = .03) and pregnancy-related morbidity (P = .001) with anti-domain IgG and for any thrombosis with aPS/PT IgG (P = .006). Use of noncriteria antiphospholipid with or without criteria markers did not significantly increase the probability to diagnose APS. Conclusions Noncriteria tests can contribute to diagnosis and stratification of APS but do not improve diagnostic yield. Optimal strategies for implementation require prospective investigation.

β2-glycoprotein I–dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3598-3602 ◽  
Author(s):  
H. Bas de Laat ◽  
Ronald H.W.M. Derksen ◽  
Rolf T. Urbanus ◽  
Mark Roest ◽  
Philip G. de Groot
Keyword(s):  
Confidence Interval ◽  
Antiphospholipid Syndrome ◽  
Partial Thromboplastin Time ◽  
Antiphospholipid Antibodies ◽  
Odds Ratio ◽  
Lupus Anticoagulant ◽  
Thromboembolic Complications ◽  
Glycoprotein I ◽  
Patients At Risk ◽  
History Of

The antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies in plasma of patients with thromboembolic complications. A major problem in defining the syndrome is that serologic assays to detect antiphospholipid antibodies have a low specificity. We recently published a method that specifically detects lupus anticoagulant (LAC) caused by anti–β2-glycoprotein I antibodies. Here, we studied the clinical relevance of detecting β2-glycoprotein I–dependent LAC. Plasma samples were collected from 198 patients with autoimmune diseases. In those samples with a positive partial thromboplastin time–lupus anticoagulant (PTT-LA), a modified activated partial thromboplastin time (aPTT)–based LAC test was performed with cardiolipin as confirming agent. Twenty-five of 58 patients with an aPTT-based LAC were dependent on the presence of anti–β2-glycoprotein I antibodies. Presence of β2-glycoprotein I–dependent LAC was almost completely associated with a history of thromboembolic complications (odds ratio, 42.3; 95% confidence interval, 194.3-9.9). An increased frequency of thrombosis was not found in 33 patients with LAC independent of anti–β2-glycoprotein I antibodies (odds ratio, 1.6; 95% confidence interval, 3.9-0.8). The use of an LAC assay with cardiolipin as confirming agent strongly improves the detection of patients at risk of thrombosis. Our findings suggest that anti–β2-glycoprotein I antibodies with LAC activity are antibodies that are responsible for the thromboembolic complications in the antiphospholipid syndrome.

The clinical relevance of the IgM isotype of antiphospholipid antibodies in the vascular antiphospholipid syndrome

2015 ◽  
Vol 136 (5) ◽  
pp. 883-886 ◽  
Author(s):  
Teresa Del Ross ◽  
Amelia Ruffatti ◽  
Serena Cuffaro ◽  
Marta Tonello ◽  
Antonia Calligaro ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Relevance ◽  
Antiphospholipid Antibodies

Diluted Russell viper-venom time improves identification of antiphospholipid syndrome in a lupus anticoagulant-positive patient population

2009 ◽  
Vol 101 (03) ◽  
pp. 577-581 ◽  
Author(s):  
Gisele Ferrard-Sasson ◽  
Sylvain Dubucquoi ◽  
Eric Hachulla ◽  
Lionel Prin ◽  
Pierre-Yves Hatron ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Odds Ratio ◽  
Patient Population ◽  
Lupus Anticoagulant ◽  
Univariate Analysis ◽  
Positive Patient ◽  
Lower Sensitivity ◽  
Operating Characteristics ◽  
Clinical Criteria ◽  
Glycoprotein I

SummaryThe objective of this retrospective study was to evaluate the potential ability of diluted Russell viper-venom time (dRVVT) to identify antiphospholipid syndrome (APS) in a lupus anticoagulant (LA)-positive patient population, already selected by other LA clotting tests. Our cohort of positive LA patients was first identified in our outpatients population by the following sensitive LA-detecting tests: Rosner index, diluted prothrombin time (dPT) and Rosove index. Then the 227 consecutive LA-positive patients were tested for dRVVT with the same blood sample. Anticardiolipin (aCL) and anti-β2-glycoprotein-I (β2GPI) autoantibodies assays were also performed. APS using Sapporo clinical criteria revised at Sydney, was found in 116 of these 227 consecutive LA-positive patients. Results of the different tests were analysed statistically. Using univariate analysis, dRVVT, dPT, IgG aCL and IgG anti-β2GPI autoantibodies were significantly associated with APS. The receiver operating-characteristics (ROC) curve defined the best cut-off value for dRVVT ratio at 1.61 with a good specificity (78%) and a lower sensitivity (53%). A multivariate analysis using a binary logistic procedure, retained the dRVVT ratio (≥ 1.61) and IgG anti-β2GPI autoantibodies (> 15 USG) as being associated with APS (p = 0.018; odds ratio [OR] 2.39; 95% confidence interval [CI] 1.2–4.7, and p = 0.0001; OR 3.2; 95% CI 1.5–6.5, respectively). To conclude, these results agree with the need for LA criteria favouring specificity over sensitivity. The use of a threshold around 1.6 for dRVVT ratio should help discriminate APS from non-APS patients.

scholarly journals La sindrome da anticorpi anti-fosfolipidi: un mare di autoanticorpi

2021 ◽  
Vol 24 (6) ◽  
pp. 187-187
Author(s):  
Eleonora Dei Rossi
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
High Titer ◽  
Small Vessel ◽  
Pulmonary Thrombosis ◽  
Systemic Disorder ◽  
Vessel Thrombosis

Antiphospholipid syndrome is an autoimmune systemic disorder characterized by arterial, venous or small vessel thrombosis in the setting of documented persistent antiphospholipid antibodies that include the lupus anticoagulant or moderate-high titer anticardiolipin or anti-β2Glycoprotein I antibodies. The paper describes a case of a 16-year-old girl with recurrent pulmonary thrombosis and antiphospolipid syndrome.

Performance of a New Global Chromogenic Assay for Protein C Pathway (HemosIL ThromboPath) in the Diagnosis of Lupus Anticoagulant and Antiphospholipid Antibodies.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2279-2279
Author(s):  
Pierre A. Toulon ◽  
Isabelle Martin-Toutain ◽  
Jean-Charles Piette ◽  
Marie-Claude Diemert ◽  
Annick Ankri
Keyword(s):  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Lupus Anticoagulant ◽  
Control Group ◽  
Test Results ◽  
Chromogenic Assay ◽  
Apc Resistance ◽  
Significant Difference ◽  
History Of ◽  
Test Result

Abstract Background: The HemosIL ThromboPath assay (Instrumentation Laboratory) is a new chromogenic assay designed to globally evaluate the functionality of the PC pathway. It is based on the ability of endogenous APC generated after activation of PC by a snake venom extract (Protac) to reduce the thrombin generation induced by a reagent containing tissue factor. Briefly, optical density is measured after addition of a thrombin-specific chromogenic substrate in the presence (OD A) or absence (OD B) of Protac. It is recommended by the test manufacturer to express results as the Protac-Induced Coagulation Inhibition percentage (PICI%) which corresponds to the ratio [OD B - OD A]/OD B x 100. Previous studies demonstrated a high sensitivity (over 96%) for PC pathway abnormalities i.e. PC/PS deficiency, and FV Leiden-related APC Resistance, but also for lupus anticoagulant (LA), known to be associated with acquired APC Resistance. The aim of the present study was to evaluate the sensitivity of that assay for antiphospholipid antibodies (APL), especially in connection with the occurrence of thrombotic complications. Actually, APL is a heterogeneous family of antibodies which have a significant impact on coagulation tests (LA) or could be detected using ELISA anticardiolipin assays (ACL). Methods: We retrospectively evaluated the frozen plasma samples from 178 patients previously diagnosed as positive for LA or as having high ACL levels. There were 48 M and 130 F with a mean age=43 years (range 14 – 87). None was on vitamin K-antagonist. Screening for LA, performed according to the ISTH criteria (Thromb Haemost1995;74:1185), was positive in 126 patients (LA+ patients) and negative in 52 patients, all of the latter having high ACL levels (LA- patients). Among LA+ patients, 41 had antiphospholipid syndrome (APS) i.e. 18 with a history of venous thrombosis (VT), 10 with arterial thrombosis (AT), 7 with obstetrical complication (OB) and 6 with combined vascular complications (CVC). The same applied to 39 LA- patients with high APL levels i.e. VT (n=13), AT (n=8), OB (n=12) and CVC (n=6). The control group consisted of 29 age- and sex-matched healthy subjects without a history of vascular or auto-immune disease. The HemosIL ThromboPath assay was performed by an operator blinded of the specific biological test results and of the clinical status of the patients. Results: Test result was significantly lower in LA+ patients than in LA- patients or in healthy controls (Table). Similarly, the percentage of abnormal test results i.e. PICI% below 85.0% as the cut-off value, was significantly higher in LA+ patients than in the two other groups (p<0.0001 in both cases). That cut-off value for the PICI% was determined, according to the recommendations of the reagent manufacturer, as the mean minus 1 SD of the values measured in the plasma of 29 healthy control subjects. Despite significantly lower PICI% in LA- patients than in controls (p<0.05), the proportion of abnormal test results was not significantly different (p<0.10) in these two groups. LA+ Patients (n=126) LA-Patients (n=52) Controls (n=29) Test Result (PICI%) 74.5 ± 13.1 86.7 ± 9.4 90.3 ± 5.3 PICI%<85% (n, %) 99 (78.6%) 15 (28.8%) 3 (10.3%) Moreover, test result was not significantly different in LA+ patients with and without a history of vascular thrombosis (PICI%=74.4 ± 12.9, n=51 vs. 74.5 ± 13.5 n=75, p=0.91) and the same applied for the percentage of abnormal test results (n=41/51 (80.4%) vs. n=58/75 (77.3%); p=0.83). There was no significant difference between LA+ patients with venous, arterial thrombosis and obstetrical complications. Conclusion: The HemosIL ThromboPath assay was highly sensitive for LA (78.6%) but it did not allow to distinguish between LA+ patients those with APS. It was found to be weakly sensitive (28.8%) to high ACL levels without LA activity, despite a higher percentage of abnormal test results. The potential interest of the HemosIL ThromboPath assay as part of the screening strategy of LA deserves to be further investigated prospectively.

Antiphospholipid syndrome: critical analysis of the diagnostic path

Lupus ◽  
2010 ◽  
Vol 19 (4) ◽  
pp. 428-431 ◽  
Author(s):  
V. Pengo ◽  
A. Banzato ◽  
E. Bison ◽  
G. Denas ◽  
S. Padayattil Jose ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Critical Analysis ◽  
Single Test ◽  
Single Class ◽  
Vascular Thrombosis ◽  
Pregnancy Morbidity ◽  
Risk Patients ◽  
Pathogenic Antibodies ◽  
Domain I

Antiphospholipid syndrome (APS) is diagnosed in the presence of vascular thrombosis or pregnancy morbidity occurring in patients with circulating antiphospholipid antibodies (lupus anticoagulant [LA] and/or IgG/IgM anticardiolipin [aCL] and/or IgG/IgM anti-β2glycoprotein I [aβ2GPI] antibodies). Each test may identify different autoantibodies; a single test makes the diagnosis possible when positive on two or more occasions at least 12 weeks apart. However, single test positivity may be unrelated to pathogenic antibodies, which are now considered to be a subclass of aβ2GPI antibodies directed against the domain I of this protein. Conversely, all three positive tests identify a single class of aβ2GPI antibodies, thus identifying high-risk patients with APS.

Correlation between antiphospholipid antibodies that recognize domain I of β2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1490-1494 ◽  
Author(s):  
Bas de Laat ◽  
Xiao-Xuan Wu ◽  
Menno van Lummel ◽  
Ronald H. W. M. Derksen ◽  
Philip G. de Groot ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Anticoagulant Activity ◽  
Annexin A5 ◽  
Anionic Phospholipids ◽  
Glycoprotein I ◽  
Group A ◽  
Group B ◽  
Domain I ◽  
American Authors

Abstract The paradoxical correlation between thrombosis and the lupus anticoagulant (LAC) effect is an enigmatic feature of the antiphospholipid (aPL) syndrome. The Dutch authors previously reported that thrombosis-related anti–β2-glycoprotein I (β2GPI) antibodies recognize domain I and cause LAC. The American authors reported that aPLs disrupt an anticoagulant annexin A5 (AnxA5) crystal shield. We investigated whether antidomain I antibodies correlate with disruption of AnxA5-anticoagulant activity. We studied a well-characterized group of 33 patients including subgroups with β2GPI-dependent LAC that recognize domain I (n = 11), with β2GPI-independent LAC (n = 12), and lacking LAC (n = 10). The effects on AnxA5-anticoagulant activity were determined with an AnxA5 resistance assay that measures coagulation times with and without AnxA5. Patients with β2GPI-dependent LAC (group A, all with thrombosis) had significantly lower AnxA5-anticoagulant ratios than those with β2GPI-independent LAC (group B, thrombosis n = 4; 157.8% versus 235.6%, P < .001) and those without LAC (group C, thrombosis n = 2; 157.8% versus 232.5%, P < .001). There was no difference in the ratios between groups B and C (P = .92). Plasmas with β2GPI-dependent LAC that recognize domain I displayed significantly increased AnxA5 resistance, suggesting that specifically anti-β2GPI antibodies compete with AnxA5 for anionic phospholipids. These results are consistent with a model in which aPL antibodies may promote thrombosis by interfering with the anticoagulant activity of AnxA5.

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