Assessment and comparison of the 2023 ACR/EULAR APS criteria with the revised Sapporo criteria.

OBJECTIVE: To analyze antiphospholipid antibody (aPL)-positive patients using the 2023 American College of Rheumatology/The European Alliance of Associations for Rheumatology (ACR/EULAR) antiphospholipid syndrome (APS) classification criteria and compare the revised Sapporo criteria and the 2023 ACR/EULAR criteria and evaluate whether the 2023 ACR/EULAR criteria provide added value over the revised Sapporo criteria. METHODS: In this descriptive study, 94 aPL-positive patients (with or without APS diagnosis) were identified from two hospital-based registries (Gazi and Hacettepe University). Patients were classified into four groups to compare both criteria sets. These four groups are as follows: (1) patients classified with only the revised Sapporo criteria; (2) patients classified with only the 2023 ACR/EULAR APS criteria; (3) patients classified with both two criteria sets; and (4) patients classified with neither two criteria set. RESULTS: Of the 94 patients, 11 were classified with only the revised Sapporo criteria; one with only the 2023 ACR/EULAR APS criteria; 52 with both criteria sets; and 30 with neither set of criteria. For these 94 patients, the operating characteristics of the 2023 ACR/EULAR APS criteria, using the revised Sapporo criteria as the gold standard, the 2023 ACR/EULAR APS entry criteria demonstrated 100% sensitivity, and the 2023 ACR/EULAR APS classification criteria demonstrated 98% specificity and 82.5% sensitivity. CONCLUSION: The study emphasizes the importance of recognizing differences in clinical manifestations, such as early pregnancy loss without severe preeclampsia (PEC) and/or severe placental insufficiency (PI) and calls for a nuanced discussion on anticardiolipin (aCL) and anti-beta 2-glycoprotein-I (anti-ß2GPI) immunoglobulin G (IgG) cutoff values.

Thrombin Generation Assay in Antiphospholipid Antibodies Positive Subjects as a Personalized Thrombotic Risk Assessment: State of the Art and Perspectives.

PURPOSE OF THE REVIEW: Thrombotic risk assessment in antiphospholipid positive (aPL +) subjects is a major challenge, and the study of in vitro thrombin generation (thrombin generation assays (TGA)) could provide useful information. Activated protein C (APC) sensitivity is involved in thrombotic events in antiphospholipid syndrome patients. We summarized methods used to assess APC sensitivity with TGA and evaluated the prognostic role of APC resistance through literature search. RECENT FINDINGS: APC resistance induced by aPL is a complex pathway. Several cross-sectional studies assessed APC sensitivity to understand thrombotic event mechanisms in aPL + subjects. Only one prospective cohort had investigated the prognostic impact of APC resistance in aPL + subjects, with a positive and significant correlation between APC sensitivity and the risk of thrombosis during the follow up (hazard ratio, 6.07 [95% CI, 1.69-21.87]). APC resistance assessed with TGA could be associated with thrombotic events in aPL + subjects.

Pediatric antiphospholipid syndrome: clinical features and therapeutic interventions in a single center retrospective case series.

BACKGROUND/PURPOSE: Pediatric antiphospholipid syndrome (APS) is a thromboinflammatory disease characterized by the presence of circulating antiphospholipid antibodies and either thrombotic events or pregnancy morbidity. The objective of this study was to review a large institution's experience to better understand the characteristics of children with APS. METHODS: We conducted a retrospective review of pediatric APS at a tertiary referral center. The electronic medical record system was queried from 2000 through 2019, and 21 cases were included based on meeting the revised Sapporo Classification criteria by age 18 or younger. Comparisons between primary and secondary APS patients were made with two-tailed t-tests. RESULTS: Twenty-one patients were included with a median age at diagnosis of 16 years and median follow-up of 5.8 years. Secondary APS was slightly more common than primary APS (11 vs. 10 cases) and was primarily diagnosed in the context of systemic lupus erythematosus. Two thirds of patients (67%) also had "non-criteria" manifestations of APS including thrombocytopenia, autoimmune hemolytic anemia, and livedo reticularis/racemosa. Almost half of patients (43%) had recurrent thrombosis, typically when patients were subtherapeutic or non-adherent with anticoagulation. Damage Index in Patients with Thrombotic APS (DIAPS) scores indicated a chronic burden of disease in both primary and secondary APS patients. CONCLUSION: This case series of pediatric APS provides important context regarding disease phenotypes displayed by children with APS. High prevalence of non-criteria clinical manifestations highlights the need to consider these characteristics when developing pediatric-specific classification criteria and when considering this relatively rare diagnosis in pediatric practice.

New insights into antiphospholipid-related endothelial dysfunction by assessment of vascular glycocalyx layer: results from a preliminary cross-sectional study.

INTRODUCTION: Antiphospholipid syndrome (APS) is associated with greater atherothrombotic risk and endothelial dysfunction, suggesting that endothelial glycocalyx is impaired in this disease. OBJECTIVES: The aim was to investigate the endothelial glycocalyx and the relationship between glycocalyx markers, endothelial dysfunction parameters and atherosclerotic markers in APS. METHODS: A total of 15 primary arterial APS patients and healthy controls were included in the study. Glycocalyx was assessed in both groups by sublingual sidestream dark field imaging and syndecan-1 plasma level. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD) and early atherosclerosis by carotid intima media thickness (IMT). Thrombotic profile was also performed by measuring the plasma level of the tissue factor (TF). RESULTS: APS patients had significantly increased syndecan-1 plasma level 38.6 ± 5.0 pg/ml vs. 19.1 ± 3.5 pg/ml; p < 0.01 and a reduced glycocalyx thickness 0.26 ± 0.03 µm vs. 0.75 ± 0.07 µm; p < 0.01 compared with control. FMD was impaired in APS patients compared with control, 5.68% ± 0.42 vs. 8.29 ± 0.30, p < 0.01, respectively. IMT was significantly increased in APS patients compared with control, 0.52 ± 0.13 mm vs. 0.40 ± 0.06 mm, p < 0.01, respectively. Soluble TF, thiobarbituric acid-reactive substances levels were increased in the sera from APS patients compared with control. CONCLUSIONS: This preliminary study supports, for the first time, that in APS patients endothelial glycocalyx is impaired, which could lead to thrombosis, endothelial dysfunction and early atherosclerosis.

Thrombotic risk assessment and analytical performance of the chemiluminescent analyzer IDS-iSYS for the detection of anti-cardiolipin and anti-beta 2 glycoprotein I autoantibodies.

Patients with antiphospholipid antibodies (APLA) are predisposed to develop thrombosis, however the standardization of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein I (ß2-GPI) Ab assays are challenging. Therefore we decided to test the performance of a new chemiluminescent assay (CLIA), and assayed aCL and aß2-GPI IgG/M in serum from 120 healthy individuals, 108 patients with idiopathic venous thrombosis, 78 patients with antiphospholipid syndrome (APS), and 64 non-thrombotic APLA-carriers using CLIA IDS-iSYS. Very good (aCL/aß2-GPI IgG) to moderate (aCL/aß2-GPI IgM) agreement with a commercial and an in house ELISA assay were observed and, in particular, CLIA demonstrated the highest sensitivity in aß2-GPI IgG detection. Finally, aCL/aß2-GPI Ab capacity to predict the thrombotic risk was tested showing for CLIA a significant odds ratio (OR) when considering double positivity for aCL/aß2-GPI IgG, aCL IgG at high levels, and aß2-GPI IgG at high levels. In conclusion, CLIA improves aß2-GPI IgG detection and thrombotic risk assessment.

Assessment of diagnostic methods for the detection of anticardiolipin and anti-ßeta2 glycoprotein I antibodies in patients under routine evaluation for antiphospholipid syndrome.

BACKGROUND: We assessed the performance characteristics and correlations of the traditional enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CIA) for detecting IgG and IgM antibodies to cardiolipin (aCL) and beta2 glycoprotein (anti-ß2GPI) antibodies in patients under routine evaluation for APS. METHODS: Patients (n = 216) referred to ARUP Laboratories for lupus anticoagulant (LAC) and/or aCL or anti-ß2GPI IgG/IgM antibodies evaluation were assessed by ELISA and CIA methods. Diagnostic accuracies, correlations between methods and specific clinical manifestations in APS were investigated. RESULTS: The areas under the curve (%) for APS using LAC with CIA (74, 95% CI: 65-82) or ELISA (70, 95% CI: 61-79) aPLs were comparable. The overall agreements and linear regression correlations between methods for aPL antibody of the same specificity were variable: aCL IgG 87.3%; R2 = 0.7491, aCL IgM 71.6%; R2 = 0.2656, anti-ß2GPI IgG 77.2%; R2 = 0.7688 and anti-ß2GPI IgM 81.7%; R2 = 0.3305. CONCLUSIONS: With inclusion of LAC, the ELISA and CIA show comparable performance for the diagnosis of APS. However, correlations of APS-specific manifestations were dependent on method of detecting the aPL antibodies suggesting platforms may not be used interchangeable.

Extra-criteria manifestations of antiphospholipid syndrome: Risk assessment and management.

OBJECTIVES: Extra-criteria manifestations of antiphospholipid syndrome (APS) might impact on prognosis and morbidity of the disease. In this study, we aimed to evaluate a population of patients with primary APS (PAPS) whether the extra-criteria manifestations were more frequently found in subjects with higher adjusted Global APS Score (aGAPSS) values when compared to patients with thrombotic and/or obstetric APS ("criteria" manifestations) only. METHODS: Clinical records were analyzed to retrieve extra-criteria manifestation of APS, cardiovascular risk factors and antiphospholipid antibodies profile. The aGAPSS was calculated by adding the points, as follows: 3 for hyperlipidaemia, 1 for arterial hypertension, 5 for anticardiolipin antibodies IgG/IgM, 4 for anti-ß2 glycoprotein I IgG/IgM, and 4 for lupus anticoagulant. RESULTS: This retrospective multicenter study included 89 consecutive PAPS [mean age 43.1 (S.D. ± 12.9), female 67%, 52% arterial and 65% venous]. Twenty-seven patients (30.3%) had a history of livedo, 19 (21.3%) had a history of confirmed thrombocytopenia, 3 (3.4%) had biopsy-proven antiphospholipid antibodies (aPL)-related nephropathy and 3 (3.4%) had a history of valvulopathy. Patients with extra-criteria manifestations presented a mean aGAPSS significantly higher [mean 10.30 (S.D. ± 3.57, range: 4-17) vs mean 8.16 (S.D. ± 3.52;range: 4-16, p = 0.005). When comparing patients with and without extra-criteria manifestations, the first group had significantly higher incidence of anti-ß2GPI antibodies positivity (59% and 33%, respectively, p = 0.015), double aPL positivities (53% and 31%, respectively, p = 0.034), cerebrovascular events history (52% and 24%, respectively, p = 0.007) and arterial hypertension (52% and 24%, respectively, p = 0.007). CONCLUSIONS: Our results suggest that patients with higher aGAPSS, might be at higher risk for developing extra-criteria manifestations of APS and should therefore undergo a thorough laboratory and instrumental evaluation.

Clinical Risk Assessment in the Antiphospholipid Syndrome: Current Landscape and Emerging Biomarkers.

PURPOSE OF REVIEW: Laboratory criteria for the classification of antiphospholipid syndrome include the detection of a lupus anticoagulant and/or anticardiolipin and anti-ß2-glycoprotein I antibodies. However, the majority of patients who test positive in these assays do not have thrombosis. Current risk-stratification tools are largely limited to the antiphospholipid antibody profile and traditional thrombotic risk factors. RECENT FINDINGS: Novel biomarkers that correlate with disease activity and potentially provide insight into future clinical events include domain 1 specific anti-ß2GPI antibodies, antibodies to other phospholipids or phospholipid/protein antigens (such as anti-PS/PT), and functional/biological assays such as thrombin generation, complement activation, levels of circulating microparticles, and annexin A5 resistance. Clinical risk scores may also have value in predicting clinical events. Biomarkers that predict thrombosis risk in patients with antiphospholipid antibodies have been long sought, and several biomarkers have been proposed. Ultimately, integration of biomarkers with established assays and clinical characteristics may offer the best chance of identifying patients at highest risk of APS-related complications.

Independent validation of the adjusted GAPSS: Role of thrombotic risk assessment in the real-life setting.

Objective The objective of this report is to independently validate the adjusted Global Antiphospholipid Syndrome Score (aGAPSS) to predict thrombosis in a cohort of patients with APS and/or autoimmune disease. Methods This retrospective cohort study included 319 consecutive patients with APS and/or autoimmune disease. Data on clinical manifestations, conventional cardiovascular risk factors and aPL profile were collected. The aGAPSS was calculated for each patient by adding together the points corresponding to the risk factors. Results Among the 319 patients included (mean age: 48.0; SD 15.47), conducted over a mean period of 52 months (range: 19-394), 219 fulfilled the current APS classification criteria (PAPS diagnosed in 130 patients and APS associated autoimmune disease (aAPS) in 89 patients), and 100 patients with autoimmune disease without APS (AD). A total of 201 patients (63.0%) had a history of one or several thrombotic manifestations, 189 (86.3%) of them APS patients: 118 PAPS (mean age: 50.14; SD 15.47) and 71 aAPS (mean age: 48.13; SD 15.81). Higher aGAPSS baseline values were seen in patients with thrombosis 6.58 (SD 3.36) when compared with those without 4.90 (SD 4.33) ( p = 0.001). Conclusions This study has shown that even when anti-phosphatidylserine/prothrombin antibodies (aPS/PT) are not computed in an adjusted model of GAPSS (aGAPSS), this score represents an improvement in assessment of the risk prediction of thrombosis in APS patients and/or autoimmune disease. However, cut-off values may differ from other kinds of cohorts, which suggests that baseline characteristics in divergent groups of patients can account for differences in cut-off values of GAPSS.

Performance Characteristics of Commercial Immunoassays for the Detection of IgG and IgM Antibodies to ß2 Glycoprotein I and an Initial Assessment of Newly Developed Reference Materials for Assay Calibration.

OBJECTIVES: To investigate the performance characteristics and impact of newly developed reference calibrators on the commutability between anti-ß2 glycoprotein I (anti-ß2 GPI) immunoassays in antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). METHODS: Immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-ß2 GPI immunoassays from four manufacturers were evaluated. Serum samples from 269 patients (APS only, n = 31; SLE and APS, n = 83; SLE only, n = 129; pregnancy-related clinical manifestations without APS, n = 26) and 162 women with histories of successful pregnancies were tested. Results were expressed in kit-specific arbitrary units and in the calibrator reference units (RUs) based on 99th percentile cutoff values. Diagnostic accuracies, correlation between kits, and specific clinical manifestations in APS were investigated. RESULTS: The sensitivities of the assays ranged from 15.8% to 27.2% (IgG) and 12.3% to 15.8% (IgM) while specificities ranged from 79.4% to 86.5% (IgG) and 80.6% to 84.5% (IgM). There was moderate to almost perfect interassay reliability (Cohen κ, 0.69-0.98), and Spearman correlation coefficients were generally improved when results of the IgG determinations were expressed in RUs. CONCLUSIONS: Although qualitative agreements between immunoassays for both antibody isotypes are acceptable, correlations with APS clinical manifestations were kit dependent. Only the use of IgG reference material improved quantitative correlations between assays.

Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies.

Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) were strongly correlated with the presence of lupus anticoagulant showing a high specificity for the diagnosis of antiphospholipid syndrome. However, the main criticism for the clinical applicability of aPS/PT testing is the lack of reproducibility of the results among laboratories. In this study, we measured IgG and IgM aPS/PT using our original in-house enzyme-linked immunosorbent assays (ELISA) and commercial ELISA kits to assess the assay performance and to evaluate the accuracy of aPS/PT results. The study included 111 plasma samples collected from patients and stored at our laboratory for aPS/PT assessment. Sixty-one samples were tested for IgG aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite™ aPS/PT IgG ELISA kit (INOVA Diagnostics, Inc., USA). Fifty samples were evaluated for IgM aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite™ aPS/PT IgM ELISA kit (INOVA Diagnostics). Ninety-eight percent of samples yielded concordant results for IgG aPS/PT and 82 % for IgM aPS/PT. There was an excellent agreement between the IgG aPS/PT assays (Cohen κ = 0.962) and moderate agreement between the IgM aPS/PT assays (κ = 0.597). Statistically significant correlations in the aPS/PT results were obtained from both IgG and IgM aPS/PT assays (r = 0.749, r = 0.622, p < 0.001, respectively). In conclusion, IgG and IgM detection by ELISA is accurate. The performance of aPS/PT is reliable, and concordant results can be obtained using different ELISA methods.

Risk assessment in patients with antiphospholipid antibodies.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the association of antiphospholipid antibodies (aPL) with thrombosis and/or pregnancy loss: classification criteria were defined in the updated international consensus held in Sidney in 2005. Vascular and obstetric manifestations display partially different pathogenetic mechanisms. Thrombosis develop as a result of local procoagulative changes upon triggers influence (second-hit theory). Pregnancy morbidity is thought to be dependent on placental thrombosis and complement activation. The laboratory tests include Lupus Anticoagulant (LA), a functional assay, and anticardiolipin (aCL) and anti-ß2-glycoprotein I antibodies detected by solid phase enzyme-linked immunosorbent assay (ELISA). The LA testing is relatively standardized while there's still significant interlaboratory discrepancy in ELISA tests. Current APS criteria are under discussion: since for vascular and obstetric APS, different pathogenetic mechanisms have been shown, some criteria variation could also be contemplated. What is the weight of aPL antibodies in provoking thrombosis and which contribution could be expected from aPL per se is debated. As thrombosis is generally considered to be multi-factorial, each case needs a risk-stratified approach. Any primary prophylaxis, intensity and duration of secondary prophylaxis should take into account aPL profile, other cardiovascular risk factors and systemic autoimmune diseases associated. We look forward to the publication of recommendations of the leading experts in the field, developed during the recent 14th International Congress in Rio de Janeiro, Brazil.

Cooperation experience in a multicentre study to define the upper limits in a normal population for the diagnostic assessment of the functional lupus anticoagulant assays.

BACKGROUND: Phospholipid-dependent coagulation tests for lupus anticoagulant (LA) are considered an important step for the diagnosis of anti-phospholipid syndrome; however, LA laboratory detection is difficult because of many variables. Five hospital laboratories, located in a North-Italy area and using the same method for LA testing, cooperated to standardise sample treatment and analytical procedure in order to define the upper values for LA negativity. METHODS: In total, 200 normal subjects (40 for each centre) were studied for six LA functional assays, using the same procedure, reagent lot and analyser type. The first tests done were LA screen and LA confirm assays, based on diluted Russell's Viper Venom Time, with low and high phospholipid content, respectively. The second tests performed were silica clotting time screen and confirm assays, based on activated partial thromboplastin time, with low and high phospholipid content, respectively. Finally, two mixing assays were executed for both screening assays, diluting patient sample with a pool prepared with plasma collected from the study population. RESULTS: Data analysis demonstrated a difference between centres for all assays when results were expressed in seconds; the difference disappeared when results are normalised with the local mean normal value of each centre and are expressed as a normalised ratio. The study population was normally distributed; so the value corresponding to 99th percentile was used as limit value for LA negativity. Values expressed as normalised ratio, for LA and silica clotting time screenings were 1.22 and 1.23, respectively. CONCLUSIONS: The study allowed us to define a uniform approach to LA testing and evaluation for laboratories employing the same methods.

Obstetric antiphospholipid syndrome.

Antiphospholipid syndrome (APS) in pregnancy has a serious impact on maternal and fetal morbidity. It causes recurrent pregnancy miscarriage and it is associated with other adverse obstetric findings like preterm delivery, intrauterine growth restriction, preeclampsia, HELLP syndrome and others. The 2006 revised criteria, which is still valid, is used for APS classification. Epidemiology of obstetric APS varies from one population group to another largely due to different inclusion criteria and lack of standardization of antibody detection methods. Treatment is still controversial. This topic should include a multidisciplinary team and should be individualized. Success here is based on strict control and monitoring throughout pregnancy and even in the preconception and postpartum periods. Further research in this field and unification of criteria are required to yield better therapeutic strategies in the future.

Risky business: the interpretation, use, and abuse of antiphospholipid antibody tests in clinical practice.

Antiphospholipid antibodies (aPL) are best considered as risk factors. aPL are not diagnostic tests and considering them as such can be misleading and may direct attention away from the more important clinical issue of risk modification and management. When considering aPL as risk factors, quantitative aPL tests such enzyme-linked immunosorbent assay (ELISA) for anticardiolipin (aCL) and anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies, should be interpreted carefully. Risk for clinical manifestations appears to be associated with moderate to high levels of these autoantibodies. Lower levels may be statistically abnormal compared with a control population, but may not be associated with the risk of thrombosis or pregnancy loss. Lupus anticoagulants (LA) are generally thought to be more strongly associated with the risk of clinical manifestation of antiphospholipid syndrome (APS) than aCL and anti-beta(2)GPI antibodies. One reason for the stronger association may be related to patients' antibody titers. LA assays are not very analytically sensitive, i.e. a relatively high concentration of antibodies is required to prolong the clotting time in these tests. Thus, the presence of LA indicates a high titer of aPL and this, rather than the intrinsic functional characteristics of LA antibodies, may explain the high risk of clinical manifestations associated with LA.

Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants.

Lupus anticoagulants (LACs) are associated with thromboembolic complications (TECs). LACs can be detected by their anticoagulant properties in thrombin generation assays, by the peak height (PH) and lag time (LT). To assess the thrombotic risk in LAC-positive patients, we have expressed the LAC activity quantitatively by PH/LT calibration curves, constructed for mixtures of monoclonal antibodies against beta2-glycoprotein I (beta2GPI) and prothrombin, spiked in normal plasma. PH/LT was determined in LAC patients, with (n = 38) and without (n = 21) TECs and converted into arbitrary LAC units. LAC titers ranged from 0 to 200 AU/mL, with 5 of 59 patients being negative. In the positive LAC titer population (54 of 59), LAC and anti-beta2GPI immunoglobulin G (IgG) titers correlated with TECs, with odds ratios of 3.54 (95% CI, 1.0-1.7) and 10.0 (95% CI, 1.98-50.6), respectively. In patients with single or combined low titers, useful predictions on thrombosis could be made only after additional measurements of soluble P-selectin and factor VII. This layered strategy yielded positive and negative predictive values, sensitivity, and specificity values approximately 90% in this subgroup. Hence, LAC and anti-beta2GPI IgG titers, when combined with selected markers of the hypercoagulable state, allow a relevant thrombotic risk assessment in nearly all patients with LACs.

Anticuerpos antifosfolípidos. Valoración clínica actual / Antiphospholipid antibodies. Current clinical assessment

El síndrome anticuerpo antifosfolipido (SAF) constituye una enfermedad autoinmune que se caracteriza por presentar trombosis vascular y abortos recurrentes, asociada a la elevación persistente de anticuerpos antifosfolípidos séricos. Los eventos trombóticos pueden ocurrir tanto en las arterias y venas como en la microcirculación. Las manifestaciones clínicas dermatológicas más frecuentes son livedo reticularis, vasculitis livedoide y úlceras, entre otras. En este trabajo se actualizan los conceptos de su etiología y los criterios diagnósticos corregidos desde el año 2004. Además se plantea un algoritmo diagnóstico y las pautas de tratamiento actuales.

Assessment of the 2006 revised antiphospholipid syndrome classification criteria.

OBJECTIVE: To analyse antiphospholipid (aPL) antibody-positive patients using the 2006 revised antiphospholipid syndrome (APS) classification criteria. METHODS: A descriptive study of 200 aPL-positive patients identified in a local, hospital-based registry, analysing demographic, clinical and aPL characteristics. Patients were analysed for (1) fulfillment of the 1999 original (Sapporo) and 2006 revised APS classification criteria; (2) non-criteria aPL features (for all aPL-positive patients, based on the 2006 revised criteria definitions); and (3) non-aPL thrombosis risk factors at the time of the clinical events (for patients with APS, based on the 2006 revised criteria stratifications). RESULTS: Of the 200 patients, 183 patients had sufficient data for analysis. Of these, 39 (21%) patients did not meet the laboratory requirement of the original 1999 criteria. Of 81 patients with APS who met the 1999 classification criteria, 47 (58%) also met the 2006 revised criteria. Of 63 asymptomatic (no vascular or pregnancy events) aPL-positive patients who met the laboratory requirement of the 1999 classification criteria, 38 (60%) also met the laboratory requirement of the 2006 revised criteria. More than 50% of the patients with APS with vascular events had identifiable non-aPL thrombosis risk factors at the time of clinical events. CONCLUSIONS: Only 59% of the patients meeting the 1999 APS Sapporo classification criteria met the 2006 APS classification criteria. The revised criteria will have positive implications in APS research by way of limiting the inclusion of a heterogeneous group of patients and also by way of providing a risk-stratified approach.