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.

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.

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 Current Promising Biomarkers and Methods in the Diagnostics of Antiphospholipid Syndrome: A Review

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 166
Author(s):  
Pavla Bradacova ◽  
Ludek Slavik ◽  
Jana Ulehlova ◽  
Adela Skoumalova ◽  
Jana Ullrychova ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Anticoagulant ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Annexin V ◽  
Protein S ◽  
Point Of View ◽  
Laboratory Diagnostics ◽  
Glycoprotein I ◽  
Domain I

Antiphospholipid syndrome (APS) is a hypercoagulation condition associated with the incidence of heterogenic antiphospholipid antibodies (aPLs), which non-specifically affect hemostasis processes. APS is clinically manifested by recurrent arterial and venous thromboses and reproduction losses. The aPL antibodies, which may induce clinical manifestations of APS, include criteria antibodies anti-cardiolipin, anti-β2-glycoprotein-I, and lupus anticoagulant, but also non-criteria antibodies, for example anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-annexin V, and many others. APS occurs mostly in patients of younger and middle age, most frequently in females. Laboratory diagnostics of APS are quite difficult, as they include a wide spectrum of examining methods, which are based on various principles of detection and are performed using various laboratory techniques. The objective of the review is to describe the current state of potentially examined biomarkers and methods in APS diagnostics. The aforementioned biomarkers are lupus anticoagulant, anti-β2-glycoprotein-I, anti-cardiolipin, anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-β2-glycoprotein-I IgA, anti-cardiolipin IgA, anti-annexin V and II, anti-prothrombin, anti-cardiolipin/vimentin, anti-protein S/protein C, and antibodies against phospholipid antigens for whose diagnostics we may use some of the methods established for a long time and some of the modern methods—the coagulation method for the determination of lupus anticoagulant (LA), enzyme-linked imunosorbent assay (ELISA), chemiluminescence analysis (CLIA), multiplex fluorescence flow immunoassay (MFFIA), fluorescence enzyme immunoassay (EliA), line immunoassay (LIA), multiline dot assay (MLDA), and thin-layer chromatography (TLC). Conclusion: Antibodies against phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, cardiolipin/vimentin complex, and annexin V are currently the most studied new markers. However, these assays have not been standardized until now, both from the laboratory and clinical point of view. In this review we summarize the evidence of the most studied aPL markers and their potential clinical significance in seronegative APS (SN-APS).

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.

scholarly journals Anti-phosphatidyl-serine/prothrombin antibodies (aPS/PT) in isolated lupus anticoagulant (LA): is their presence linked to dual test positivity?

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Marta Tonello ◽  
Elisa Bison ◽  
Maria Grazia Cattini ◽  
Elena Pontara ◽  
Luca Iaccarino ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Anticoagulant ◽  
Phosphatidyl Serine ◽  
Positive Test ◽  
Clotting Time ◽  
Glycoprotein I ◽  
Coagulation Tests ◽  
Group 2 ◽  
Positive Results ◽  
Group 1

Abstract Objectives Anti phosphatidylserine/prothrombin antibodies (aPS/PT) are often present in patients with antiphospholipid syndrome (APS) and might be relevant in the pathogenesis of this condition. They are major determinant of lupus anticoagulant (LA) in triple-positive antiphospholipid (aPL) profile. Whether they are present and pathogenic in patients with isolated LA [negative anticardiolipin (aCL) and anti β2-Glycoprotein I (aβ2GPI) antibodies] is a matter of debate. Methods We measured aPS/PT in a large number of isolated LA with the aim to ascertain whether there is a link between the way isolated LA is assessed and the presence of these antibodies. APS/PT were measured in 86 patients with isolated LA (aCL- and abeta2GPI-). LA was assessed by two test systems, the dilute Russell Viper Venom Time (dRVVT) and the Silica Clotting Time (SCT). Results Sixty-six (77%) individuals with isolated LA were positive for aPS/PT (IgM 44, IgG and IgM 15, IgG in 7). Diagnosis of LA was made based on positive results in both dRVVT and SCT in 40 patients (Group 1) and based on only one positive test in the remaining 46 patients (Group 2). The rate of positive aPS/PT antibodies was significantly higher in Group 1 (OR=7.2, 95% CI 1.9–27.0, p<0.002). Moreover, the titre of IgM aPS/PT was significantly increased in Group 1 as compared to Group 2 (137 U, IQR 64–179 vs. 43 U, IQR 11–120, p=0.008). Conclusions These data indicate an association between LA based on two positive coagulation tests and the presence of aPS/PT antibodies, especially of IgM isotype.

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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