Classification Criteria For Definite Antiphospholipid Syndrome Research Articles

Insight into antiphospholipid syndrome: the role and clinical utility of neutrophils extracellular traps formation

Antiphospholipid syndrome (APLS) is a systemic immune dysregulation distinguished by repetitive complications and pregnancy loss in the absence of definite etiology. Most research focuses on the laboratory detection and clinical features of APLS, but its precise etiology remains to be deeply explored. NETosis is a newly developed theory in the pathophysiology of APLS which may serve as the missing bridge between coagulation and inflammation reaching the disease progression and severity. We aimed in this study to navigate the prognostic role of NETosis in thrombotic APLS. Our study included 49 newly diagnosed APLS patients (both 1ry and 2ry) who met clinical and laboratory criteria as per the international consensus statement on the update of the classification criteria for definite APLS and were sub-classified according to the occurrence of thrombotic events in thrombotic and non-thrombotic types. In addition, 20 sex and age-matched reactive subjects and 20 sex and age-matched healthy volunteer controls were enrolled. NETosis formation was assessed by measuring serum Myeloperoxidase (MPO) and Histones level using the enzyme-linked immunosorbent assay (ELISA) technique. Both MPO and Histones levels were able to discriminate among APLS cases from normal controls, showing significant cutoffs of > 2.09 ng/ml for MPO and > 1.45 ng/ml for Histones (AUC values were 0.987and 1.000, respectively). These values can be used as predictors for NETosis pathophysiology in APLS patients. Additionally, these markers demonstrated a significant association with several prognostic indicators, including thrombosis, higher PT and INR, and lower hemoglobin (Hb) levels which are supposed to be ameliorated by using NETs inhibitors. In conclusion, we suggest that measuring NETosis markers, MPO, and Histones, in the early course of APLS using proposed cutoff values will facilitate the timely initiation of anti-NETosis therapy and improve the overall prognosis, particularly for patients with thrombotic APLS.

Antiphospholipid syndrome and direct oral anticoagulants: to the future and back again?

Antiphospholipid syndrome and direct oral anticoagulants: to the future and back again?

Current treatment of antiphospholipid syndrome: lights and shadows.

For patients with antiphospholipid syndrome (APS), the consensus is to treat those who develop thrombosis with long-term oral anticoagulation therapy and to prevent obstetric manifestations by use of aspirin and heparin. These recommendations are based on data from randomized controlled trials and observational studies. Despite this body of knowledge, areas of uncertainty regarding the management of APS exist where evidence is scarce or nonexistent. In other words, for a subset of patients the course of management is unclear. Some examples are patients with 'seronegative' APS, those who do not fulfil the formal (clinical or serological) classification criteria for definite APS, and those with recurrent thrombotic events despite optimal anticoagulation. Other challenges include the treatment of clinical manifestations not included in the classification criteria, such as haematologic manifestations (thrombocytopenia and haemolytic anaemia), neurologic manifestations (chorea, myelitis and multiple sclerosis-like lesions), and nephropathy and heart valve disease associated with antiphospholipid antibodies (aPL), as well as the possible withdrawal of anticoagulation treatment in selected cases of thrombotic APS in which assays for aPL become persistently negative. This Review focuses on the current recommendations for thrombotic and obstetric manifestations of APS, as well as the management of difficult cases. Some aspects of treatment, such as secondary prophylaxis of venous thrombosis, are based on strong evidence--the 'lights' of APS treatment. Conversely, other areas, such as the treatment of non-criteria manifestations of APS, are based only on expert consensus or common sense and remain the 'shadows' of APS therapy.

Standards and reference materials for the anticardiolipin and anti-β2glycoprotein I assays: A report of recommendations from the APL Task Force at the 13th International Congress on Antiphospholipid Antibodies

BackgroundThe confirmation of diagnosis of the Antiphospholipid Syndrome (APS) relies on laboratory tests. Current classification criteria for definite APS mandate the use of three “standardized” laboratory assays to detect antiphospholipid antibodies (aPL) [viz: anticardiolipin (aCL) IgG and IgM, anti-β2glycoprotein I (anti-β2GPI) antibodies IgG and IgM and/or a lupus anticoagulant (LAC)], when at least one of the two major clinical manifestations (thrombosis or pregnancy losses) are present. Several attempts have been made to standardize the aCL and anti-β2GPI tests, though, a considerable degree of inconsistencies still exist, limiting the clinical and diagnostic value of aPL tests. Among the areas of concern are the type and source of calibrant material, the lack of proper validated reference material and of universal units of measurement, particularly for anti-β2GPI antibodies. ContentA Task Force of scientists and leaders in the field from different countries — discussed and analyzed those critical questions in an evidence-based manner and further discussed and made recommendations at a workshop that was conducted during 13th International Congress on Antiphospholipid Antibodies (APLA 2010, April 13–16, 2010, Galveston, TX). SummaryThis concise report summarizes the findings, conclusions and recommendations of the task force and preconference workshop. The group recommended to ensure the availability of properly prepared and validated polyclonal and monoclonal antibody reference materials for both assays, to continue reporting the aCL assay in GPL/MPL units and to establish consensus international units of measurement for anti-β2GPI antibodies.

Microthrombotic/Microangiopathic Manifestations of the Antiphospholipid Syndrome

The paper presents an overview of clinical manifestations and histopathologic findings in different organs in microvascular thrombotic and microangiopathic antiphospholipid syndrome (MAPS). Subsets of antiphospholipid syndrome (APS) are presented and defined. Clinico-pathologic correlations seem insufficient so far, because of a lack of detailed systematic studies of the histopathology in different organs. Based on their own autopsy and biopsy studies, the authors propose a novel categorization of histopathologic lesions that occur in patients with classic and catastrophic APS. In addition to the already accepted category of a microvascular thrombotic type of lesions, microangiopathic lesions consistent with thrombotic microangiopathy are proposed to be included in new revised classification criteria for definite APS. Microvascular thrombotic and so far underestimated microangiopathic histopathologic lesions have been shown to appear in various combinations and of different ages in patients with both classic and catastrophic APS, which fits into the concept of MAPS. These preliminary findings of our studies are also in line with the most recent hypothesis of two main mechanisms in the pathogenesis of APS, emphasizing a key role of endothelial cell affection induced by aPL on the one hand and interference with coagulation cascade on the other side.

Specificity and sensitivity of anti-β2-glycoprotein I as compared with anticardiolipin antibody and lupus anticoagulant in Thai systemic lupus erythematosus patients with clinical features of antiphospholipid syndrome

Antibodies to beta(2)-glycoprotein I (anti-beta(2)-GPI) have been reported to have stronger association with clinical antiphospholipid syndrome (APS) than anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). We investigated the sensitivity and specificity of ELISA for anti-beta(2)-GPI in Thai systemic lupus erythematosus (SLE) patients with clinical features of APS and compared the results with IgG/IgM aCL and LAC to find the test with the best association. The hospital records of 151 Thai SLE patients whose sera had been sent for either IgG/IgM anticardiolipin antibodies or lupus anticoagulant testing were reviewed. Sera of patients either without complete clinical records or those with APS-related manifestations other than vascular thrombosis and pregnancy morbidity (according to the international consensus statement on preliminary classification criteria for definite APS) were excluded. For the remaining subjects (112 patients), their sera were tested for anti-beta(2)-GPI antibody, IgG and IgM anticardiolipin, and lupus anticoagulant. The sensitivity and specificity of each method were compared by using the chi-square test. Among the 112 (74.2%) SLE patients in the study, 35 (31.3%) presented with preliminary clinical criteria for APS (i.e., vascular thrombosis and pregnancy morbidity) whereas 77 (68.7%) did not. The sensitivity and specificity of anti-beta(2)-GPI determination were 57.1 and 79.2%, respectively, whereas those of IgG aCL were 25.7 and 94.8%, of IgM aCL were 5.7 and 98.7%, and of LAC were 44.8 and 77.3%, respectively. The accuracy of the four tests showed similar association with clinical APS (accuracy of test = 72.3, 73.2, 69.6, and 68.3%, respectively). Concerning the sensitivity, specificity, and difficulty of the methods, the combination of anti-beta(2)-GPI and IgG aCL tests was the best for the diagnosis of APS in Thai SLE patients.

Antibody specificity and related clinical features in antiphospholipid syndrome

The concept of antiphospholipid syndrome (APS) has been widely accepted. Antiphospholipid antibodies originally included anticardiolipin antibodies and lupus anticoagulants. However, recent advances have shown that most pathogenic antiphospholipid antibodies are directed to phospholipid binding proteins such as β2-glycoprotein I (β2-GPI) and prothrombin. Other candidates for antigens of so-called antiphospholipid antibodies are protein C, protein S, factor V, factor X, annexin V, high and low molecular weight kininogens, and complex with β2-GPI and oxidized low-density lipoprotein (LDL). These autoantibodies directed to different phospholipid binding proteins are present in the blood stream, and contribute to triggering procoagulant effects on endothelial cells and platelets, leading to thrombosis. The heterogeneity of these antiphospholipid antibodies appears to explain various clinical manifestations in patients with APS. The preliminary classification criteria for definite APS and a general management policy have been proposed, although successful treatment of patients with antiphospholipid antibodies have only been shown by retrospective studies. Further prospective investigations are required to confirm the diagnostic and therapeutic criteria for patients with APS.