Diagnosis and therapy of antiphospholipid syndrome (original) (raw)
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Arthritis & Rheumatism, 2012
ObjectiveTo define the antiphospholipid score (aPL‐S) by testing multiple antiphospholipid antibodies (aPL) and to evaluate its efficacy for the diagnosis of antiphospholipid syndrome (APS) and predictive value for thrombosis.MethodsThis study comprised 2 independent sets of patients with autoimmune diseases. In the first set of patients (n = 233), the aPL profiles were analyzed. Five clotting assays for testing lupus anticoagulant and 6 enzyme‐linked immunosorbent assays (IgG/IgM anticardiolipin antibodies, IgG/IgM anti–β2‐glycoprotein I, and IgG/IgM phosphatidylserine‐dependent antiprothrombin antibodies) were included. The association of the aPL‐S with a history of thrombosis/pregnancy morbidity was assessed. In the second set of patients (n = 411), the predictive value of the aPL‐S for thrombosis was evaluated retrospectively. Two hundred ninety‐six of these patients were followed up for >2 years. The relationship between the aPL‐S and the risk of developing thrombosis was an...
Laboratory Evaluation of the Antiphospholipid Syndrome
Hematology/Oncology Clinics of North America, 2008
Th e antiphospholipid syndrome (APS) was fi rst described in 1986. Th e original association of this hypercoagulable state with anticardiolipin antibodies (aCL) resulted from the synthesis of evidence stemming from laboratory fi ndings in systemic lupus erythematosus (SLE), ie, the frequent occurrence of false-positive VDRL tests and the paradoxical observation of the so-called "lupus anticoagulant" (LA), an increase in phospholipid (PL)-dependent clotting times. By the early 1990s, it was clear that a co-factor was involved in the reaction of antibodies to PL (aPL) in SLE patients with secondary APS and that this was a hitherto-obscure protein, beta-2 glycoprotein I (β2GPI). In the intervening years, it has been established that β2GPI and other PL-binding proteins such as prothrombin (PT) are relevant antigens in APS and assays for these antigens have been developed, standardized, and applied to subjects with both primary and secondary APS. Measurement and confi rmation of LA activity is based on a stepwise approach and should follow the recommendations of the International Society of Th rombosis and Haemostasis. Although antibodies to various PL-binding proteins have been suggested as diagnostic targets for APS, the current (2006) consensus guidelines recognize only LA, aCL, and anti-β2GPI for the classifi cation of APS.
Diagnosis of antiphospholipid syndrome in routine clinical practice
Lupus, 2013
The updated international consensus criteria for definite antiphospholipid syndrome (APS) are useful for scientific clinical studies. However, there remains a need for diagnostic criteria for routine clinical use. We audited the results of routine antiphospholipid antibodies (aPLs) in a cohort of 193 consecutive patients with aPL positivity-based testing for lupus anticoagulant (LA), IgG and IgM anticardiolipin (aCL) and anti-ß 2 glycoprotein-1 antibodies (aß 2 GPI). Medium/high-titre aCL/ab 2 GPI was defined as >99th percentile. Low-titre aCL/ab 2 GPI positivity (>95 th < 99 th percentile) was considered positive for obstetric but not for thrombotic APS. One hundred of the 145 patients fulfilled both clinical and laboratory criteria for definite APS. Twenty-six women with purely obstetric APS had persistent low-titre aCL and/or ab 2 GPI. With the inclusion of these patients, 126 of the 145 patients were considered to have APS. Sixty-seven out of 126 patients were LA-negative, of whom 12 had aCL only, 37 had ab 2 GPI only and 18 positive were for both. The omission of aCL or ab 2 GPI testing from investigation of APS would have led to a failure to diagnose APS in 9.5% and 29.4% of patients, respectively. Our data suggest that LA, aCL and ab 2 GPI testing are all required for the accurate diagnosis of APS and that low-titre antibodies should be included in the diagnosis of obstetric APS. Lupus (2013) 22, 18-25.
Journal of Thrombosis and Haemostasis, 2012
To evaluate the clinical accuracy of antiphospholipid antibody (aPL) specificities both individually and/or in combination, in a wide cohort of systemic lupus erythematosus (SLE) patients in an attempt to identify a panel of tests that may provide the best accuracy for diagnosing antiphospholipid syndrome (APS). Patients and Methods:This study included 230 patients (218 women, mean age 42.7 ± 11.9 years, mean disease duration 12.2 ± 8.7 years), all fulfilling the 1982 criteria for SLE. All patients were tested for lupus anticoagulant (LA), anti-cardiolipin (aCL), anti-β 2glycoprotein I (anti-β2GPI), solid phase anti-prothrombin (aPT), anti-phosphatidylserine/prothrombin (aPS/PT), and antiphosphatidylethanolamine (aPE) antibodies. Sensitivity, specificity and predictive values were calculated. The diagnostic accuracy for each combination of tests was assessed by ROC and their area under the curve analysis as well as by the Youden's index (YI). Results:Testing for six aPL derived 23 possible combinations of results. Among them, LA + anti-β 2GPI + aPS/PT had the best diagnostic accuracy for APS as a whole and individually for both thrombosis and pregnancy loss (AUC 0.712, OR 3.73 [95% CI 1.82-5.38],P = 0.0001, YI = 0.32 and AUC 0.709, OR 3.75 [95% CI 2.13-6.62], P = 0.0001, YI = 0.37 and AUC 0.677, OR 4.82 [95% CI 2.17-10.72], P = 0.0007, YI = 0.38, respectively) and the best specificity when compared with all the other obtainable combination of tests. Triple positivity for LA + anti-β2GPI + aPS/PT was more strongly associated with clinical events (thrombosis and/or PL) when compared with double or single positivity (OR 23.2 [95% CI 2.57-46.2] vs. OR 7.3 [95% CI 2.21-25.97], OR 5.7 [95% CI 2.12-17.01] or OR 3.11 [95% CI 1.56-7.8] for single positivity for LA, aPS/PT and anti-β2GPI, respectively). Conclusions:Combining LA, anti-β 2GPI and aPS/PT improves the diagnostic power and helps in stratifying the risk for each patient, according to their aPL profile.
Antiphospholipid Antibody Syndrome-Diagnostic Issues of Lupus Anticoagulants
Journal of Hematology & Thromboembolic Diseases
Antiphospholipid antibody syndrome is a serious autoimmune disorder which can lead to multisystem manifestations from recurrent thrombosis to pregnancy loss to intrauterine death and other obstetric morbidities. In few cases it may lead to catastrophic syndrome. Antiphospholipid antibodies are circulating antibodies which bind with the plasma proteins which in turn bind to phospholipids and thus lead to pathogenesis. Despite of so many researches done in the field of APLA, the mechanisms leading to obstetric complications are still debatable. Antiphospholipid antibodies are detected on the basis of solid phase assays which comprised of anticardiolipin (acl) antibody and Anti β2 glycoprotein (aB2GP) and the other one is liquid phase assays which identifies lupus anticoagulants (LAC). While aB2GP and acl are being detected most commonly by ELISA, LAC is being detected by clot based test. Lupus anticoagulant is a double misnomer as most patients don't have systemic lupus erythematous and in vivo reacts as procoagulants.
How we diagnose the antiphospholipid syndrome
Blood, 2008
The antiphospholipid syndrome (APS) is an acquired thrombophilia, characterized by the occurrence of venous and arterial events. This article examines the laboratory and key clinical aspects of APS. Particular focus is given to anti–beta 2-glycoprotein I (β2GPI) antibodies in view of their recent inclusion in the APS classification criteria. The clinical utility of using the β2GPI enzyme-linked immunosorbent assay, in conjunction with the established lupus anticoagulant assays and cardiolipin enzyme-linked immunosorbent assay, for diagnosing and risk stratifying patients suspected of having APS is discussed. The relative importance of the various assays in diagnosing obstetric APS (early and late gestation miscarriages) is explored. The implications of recent epidemiologic findings for possibly understanding the underlying pathophysiologic mechanisms of obstetric APS are highlighted. Insights into which patients with obstetric APS may be at most risk of thrombotic complications are ...
Diagnosis and classification of the antiphospholipid syndrome
The antiphospholipid syndrome (APS) is defined by the occurrence of venous and arterial thromboses, often multiple, and recurrent fetal losses, frequently accompanied by a moderate thrombocytopenia, in the presence of antiphospholipid antibodies (aPL). Some estimates indicate that the incidence of the APS is around 5 new cases per 100,000 persons per year and the prevalence around 40e50 cases per 100,000 persons. The aPL are positive in approximately 13% of patients with stroke, 11% with myocardial infarction, 9.5% of patients with deep vein thrombosis and 6% of patients with pregnancy morbidity. The original classification criteria for the APS were formulated at a workshop in Sapporo, Japan, in 1998, during the 8th International Congress on aPL. The Sapporo criteria, as they are often called, were revised at another workshop in Sydney, Australia, in 2004, during the 11th International Congress on aPL. At least one clinical (vascular thrombosis or pregnancy morbidity) and one laboratory (anticardiolipin antibodies, lupus anticoagulant or anti-b 2 -glycoprotein I antibodies) criterion had to be met for the classification of APS.
Journal of Immunology Research, 2015
Antiphospholipid syndrome (APS) is characterized by development of venous and/or arterial thrombosis and pregnancy morbidity. Biological criteria are the persistent presence of lupus anticoagulant (LA) and/or anti-cardiolipin (aCL) and/or anti-B2GP1 autoantibodies’ positivity. The assays’ performances are of crucial importance. We evaluated a multiplex assay allowing simultaneous detection of IgG anti-cardiolipin, anti-B2GP1, and anti-factor II. 300 samples were tested. Patients were categorized according to clinical scores of APS from 0 to 3 based on presence or not of arterial or venous thrombosis, fetal loss, and autoimmunity. We used a multiplex assay for APS for simultaneous detection of aCL, anti-B2GP1, and factor II and compared its performances to ELISA assays. Presence of LA was also assessed. We performed a correlation study of the tested assays and compared their clinical efficacy by ROC curve analysis. We obtained significantly higher performances with the multiplex assa...