Relationship between antiphosphatidylserine/prothrombin and conventional antiphospholipid antibodies in primary antiphospholipid syndrome

2015 ◽  
Vol 53 (8) ◽  
Author(s):  
Ariela Hoxha ◽  
Amelia Ruffatti ◽  
Elena Mattia ◽  
Lauro Meneghel ◽  
Marta Tonello ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Primary Antiphospholipid Syndrome ◽  
Clinical Criteria ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Coagulation Tests ◽  
Healthy Control ◽  
Independent Risk Factors ◽  
Ig G

AbstractAntiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are emerging as an important marker for antiphospholipid syndrome (APS). We aimed to compare their performance with that of conventional antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2-glycoprotein I (anti-β2GPI) in APS and to assess their frequency in APS-negative (APS-ne) patients.We considered 160 APS patients and 128 APS-ne patients with clinical criteria for APS but tested negative for conventional aPL. Immunoglobulin (Ig)G/IgM aPS/PT, IgG/IgM aCL, and IgG/IgM anti-β2GPI were detected using ELISA assay and LA with a series of coagulation tests.IgG aPS/PT were significantly associated with IgG aCL, IgG anti-β2GPI, and LA (p<0.0001 for all). IgM aPS/PT were significantly associated only with LA (p<0.0001) instead. There was a significant correlation between IgG aPS/PT and both IgG aCL and IgG anti-β2GPI levels (ρ=0.42 and ρ=0.40, respectively). Both IgG aPS/PT and IgM aPS/PT positivity significantly correlated with LA (ρ=0.44 and ρ=0.5, respectively). IgG and IgM aPS/PT were significantly more frequent in triple than in double and in single positivity (p<0.0001). According to multivariate analysis, IgG and/or IgM aPS/PT were independent risk factors for LA. APS/PT antibodies were found in 9.4% of the APS-ne patients vs. 2% of healthy control (p=0.043); those antibodies were significantly more frequent in the thrombosis with respect to the pregnancy morbidity subset (p=0.01).Our data attribute a clinical relevance to both IgG and IgM aPS/PT antibodies. In particular, the significant prevalence of aPS/PT in APS-ne patients suggests including them as additional laboratory criterion for APS.

scholarly journals Challenges in the Diagnosis of the Antiphospholipid Syndrome

2010 ◽  
Vol 56 (6) ◽  
pp. 930-940 ◽  
Author(s):  
Katrien Devreese ◽  
Marc F Hoylaerts
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Complex Disease ◽  
Clinical Manifestations ◽  
Clinical Role ◽  
Clinical Criteria ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Coagulation Tests

Abstract Background: The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. Its diagnosis is based on clinical and laboratory criteria, defined by strict guidelines. The original clinical and laboratory criteria for the identification of APS patients were published in 1999, in the so-called Sapporo criteria. In 2006 these criteria were revised, and recently more precise guidelines for analysis of the lupus anticoagulant have been provided. However, several questions related to the diagnosis of APS remain unanswered. Content: In addition to providing a historical perspective, this review covers several challenges in the diagnosis of APS with respect to clinical and laboratory features, while highlighting pathogenic pathways of the syndrome. We discuss ongoing dilemmas in the diagnosis of this complex disease. Although antiphospholipid antibodies are found in association with various clinical manifestations, the older established clinical criteria were not substantively altered in the 2006 update. Several laboratory tests recommended in the latest criteria, including phospholipid-dependent coagulation tests for the detection of the lupus anticoagulant and ELISAs for measuring anticardiolipin and β2-glycoprotein I antibodies, still show methodological and diagnostic shortcomings. In addition, antiphospholipid antibodies have been described against other antigens, but their clinical role remains uncertain. Conclusions: Despite updated APS criteria, diagnosis of this syndrome remains challenging. Further research on clinically relevant antibodies and standardization of their detection are needed to improve clinical risk assessment in APS.

scholarly journals Recent advances in understanding antiphospholipid syndrome

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2908 ◽  
Author(s):  
Maria Laura Bertolaccini ◽  
Giovanni Sanna
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Anticardiolipin Antibodies ◽  
Coagulation Cascade ◽  
Systemic Autoimmune Disease ◽  
Vascular Thrombosis ◽  
Clinical Criteria ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Hughes Syndrome

Antiphospholipid syndrome (APS), also known as Hughes Syndrome, is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. A patient with APS must meet at least one of two clinical criteria (vascular thrombosis or complications of pregnancy) and at least one of two laboratory criteria including the persistent presence of lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and/or anti-b2 glycoprotein I (anti-b2GPI) antibodies of IgG or IgM isotype at medium to high titres in patient’s plasma. However, several other autoantibodies targeting other coagulation cascade proteins (i.e. prothrombin) or their complex with phospholipids (i.e. phosphatidylserine/prothrombin complex), or to some domains of β2GPI, have been proposed to be also relevant to APS. In fact, the value of testing for new aPL specificities in the identification of APS in thrombosis and/or pregnancy morbidity patients is currently being investigated.

scholarly journals Isolated IgA Anti-β2 Glycoprotein I Antibodies in Patients with Clinical Criteria for Antiphospholipid Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Raquel Ruiz-García ◽  
Manuel Serrano ◽  
José Ángel Martínez-Flores ◽  
Sergio Mora ◽  
Luis Morillas ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Clinical Manifestations ◽  
Diagnostic Systems ◽  
Clinical Criteria ◽  
Glycoprotein I ◽  
Standardized Diagnostic ◽  
Disease Present

Seronegative antiphospholipid syndrome (SNAPS) is an autoimmune disease present in patients with clinical manifestations highly suggestive of Antiphospholipid Syndrome (APS) but with persistently negative consensus antiphospholipid antibodies (a-PL). IgA anti-β2 Glycoprotein I (aB2-GPI) antibodies are associated with APS. However, they are not currently considered to be laboratory criteria due to the heterogeneity of published works and the use of poor standardized diagnostic systems. We have aimed to assess aPL antibodies in a group of patients with clinical manifestations of APS (C-APS) to evaluate the importance of the presence of IgA aB2GPI antibodies in APS and its relation with other aPL antibodies. Only 14% of patients with C-APS were positive for any consensus antibody, whereas the presence of isolated IgA aB2GPI antibodies was found in 22% of C-APS patients. In patients with arterial thrombosis IgA aB2GPI, antibodies were the only aPL antibodies present. Serologic profile in primary APS (PAPS) is different from systemic autoimmune disorders associated APS (SAD-APS). IgA aB2GPI antibodies are more prevalent in PAPS and IgG aB2GPI antibodies are predominant in SAD-APS. The analysis of IgA aB2GPI antibodies in patients with clinical manifestations of PAPS might avoid underdiagnosed patients and provide a better diagnosis in patients with SAD-APS. Laboratory consensus criteria might consider including analysis of IgA aB2GPI for APS diagnosis.

Complement activation in patients with isolated antiphospholipid antibodies or primary antiphospholipid syndrome

2012 ◽  
Vol 107 (03) ◽  
pp. 423-429 ◽  
Author(s):  
Paul Seed ◽  
Kiran Parmar ◽  
Gary W. Moore ◽  
Sara E. Stuart-Smith ◽  
Beverley J. Hunt ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Complement Activation ◽  
Antiphospholipid Antibodies ◽  
High Titre ◽  
Primary Antiphospholipid Syndrome ◽  
Pregnancy Morbidity ◽  
Activation Products ◽  
Cardiolipin Antibodies ◽  
Patient Groups ◽  
Obstetric Aps

SummaryThe antiphospholipid syndrome (APS) is the association of thrombosis and recurrent pregnancy loss and/or pregnancy morbidity with persistent antiphospholipid antibodies (aPL). Increased complement activation has been implicated in the pathogenesis of APS in animal models. It was our objective to evaluate complement activation in patients with aPL or primary antiphospholipid syndrome (PAPS). We measured complement activation products, fragments Bb and C3a–desArg by ELISA in 186 aPL/PAPS patients and 30 healthy controls. All patients with aPL had significantly increased levels of complement activation products. Fragment Bb levels (mean, 95% CI); (thrombotic APS 0.54 units/ml, 0.31–0.83, obstetric APS 0.60 units/ml,0.39–1.02, isolated aPL 0.48 units/ml, 0.29–0.85, overall 0.39 units/ml, 0.33–0.47) and C3a–desArg levels (mean, 95% CI): (thrombotic APS 261 ng/ml, 219–311, obstetric APS 308 ng/ml, 243–391, isolated aPL 258 ng/ml, 193–337, overall 225 ng/ml, 202–251) were significantly higher compared to controls (fragment Bb 0.06 units/ml, 0.03–0.11, C3a–desArg 69 ng/ml, 50–92). There were correlations between Fragment Bb and C3a–desArg levels in all patients with aPL. Receiver operator characteristic (ROC) analysis showed increased fragment Bb and C3a–desArg levels had strong associations with the presence of persistent lupus anticoagulant (area under ROC: Bb 0.89, and C3a–desArg 0.90), dual and triple aPL positivity (Bb 0.71–0.82, C3a–desArg 0.71–0.80) but not with high titre anti-cardiolipin antibodies (Bb 0.62, C3a–desArg 0.65), or anti β2-glycoprotein 1 antibodies (Bb 0.66, C3a–desArg 0.67). Complement activation is present in all patient groups within this large cohort of patients aPL. This suggests it may have a major role in the pathogenesis of APS and merits further study.

Diagnosis and management of non-criteria obstetric antiphospholipid syndrome

2015 ◽  
Vol 113 (01) ◽  
pp. 13-19 ◽  
Author(s):  
Samuel J. Machin ◽  
Ian J. Mackie ◽  
Hannah Cohen ◽  
Deepa R. Jayakody Arachchillage
Keyword(s):  
Antiphospholipid Syndrome ◽  
In Vitro Fertilisation ◽  
International Consensus ◽  
Clinical Criteria ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Retrospective Cohort Studies ◽  
Obstetric Antiphospholipid Syndrome ◽  
Obstetric Aps

SummaryAccurate diagnosis of obstetric antiphospholipid syndrome (APS) is a prerequisite for optimal clinical management. The international consensus (revised Sapporo) criteria for obstetric APS do not include low positive anticardiolipin (aCL) and anti β2 glycoprotein I (aβ2GPI) antibodies (> 99th centile) and/or certain clinical criteria such as two unexplained miscarriages, three non-consecutive miscarriages, late preeclampsia, placental abruption, late premature birth, or two or more unexplained in vitro fertilisation failures. In this review we examine the available evidence to address the question of whether patients who exhibit non-criteria clinical and/or laboratory manifestations should be included within the spectrum of obstetric APS. Prospective and retrospective cohort studies of women with pregnancy morbidity, particularly recurrent pregnancy loss, suggest that elimination of aCL and/or IgM aβ2GPI, or low positive positive aCL or aβ2GPI from APS laboratory diagnostic criteria may result in missing the diagnosis in a sizeable number of women who could be regarded to have obstetric APS. Such prospective and retrospective studies also suggest that women with non-criteria obstetric APS may benefit from standard treatment for obstetric APS with low-molecular-weight heparin plus low-dose aspirin, with good pregnancy outcomes. Thus, non-criteria manifestations of obstetric APS may be clinically relevant, and merit investigation of therapeutic approaches. Women with obstetric APS appear to be at a higher risk than other women of pre-eclampsia, placenta- mediated complications and neonatal mortality, and also at increased long-term risk of thrombotic events. The applicability of these observations to outcomes in women with non-criteria obstetric APS remains to be determined.

The significance of autoantibodies against β2-glycoprotein I

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 266-274 ◽  
Author(s):  
Philip G. de Groot ◽  
Rolf T. Urbanus
Keyword(s):  
Autoimmune Disease ◽  
Infectious Diseases ◽  
Antiphospholipid Syndrome ◽  
Plasma Protein ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Thrombotic Risk ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
History Of

AbstractThe antiphospholipid syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with a history of thrombosis and/or pregnancy morbidity, including fetal loss. APS is an autoimmune disease with a confusing name because the pathologic auto-antibodies are shown to be directed against the plasma protein β2-glycoprotein I and not against phospholipids. In fact, auto-antibodies that recognize phospholipids themselves are not associated with thrombosis but with infectious diseases. One of the intriguing questions is why autoantibodies against β2-glycoprotein I are so commonly found in both patients and the healthy. Several potential mechanisms have been suggested to explain the increased thrombotic risk in patients with these autoantibodies. In this overview, we will summarize our knowledge on the etiology of the autoantibodies, and we will discuss the evidence that identify autoantibodies against β2-glycoprotein I as the culprit of APS.

Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity

2006 ◽  
Vol 96 (09) ◽  
pp. 337-341 ◽  
Author(s):  
Amelia Ruffatti ◽  
Marta Tonello ◽  
Teresa Del Ross ◽  
Anna Cavazzana ◽  
Chiara Grava ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Pregnancy Loss ◽  
Late Pregnancy ◽  
Primary Antiphospholipid Syndrome ◽  
Thromboembolic Events ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
History Of ◽  
Classification Category

SummaryIn women diagnosed as having category I primary obstetric antiphospholipid syndrome, clinical characteristics and the risk of subsequent thromboembolic events and further unsuccessful pregnancy has not been clearly documented. Women with unexplained obstetric complications and no definite autoimmune systemic diseases were tested for lupus anticoagulant (LA), IgG/ IgM anticardiolipin (aCL) and IgG/IgM anti-human β2-Glycoprotein I (aβ2GPI) antibodies and diagnosed as having primary antiphospholipid syndrome (APS) in classification category I on the basis of more than one laboratory criteria present in any combination. Characteristics at the time of diagnosis and risk factors for subsequent clinical events during a mean follow-up of 6.3 years were evaluated. Fifty-three of 600 women studied were found to fulfil obstetric criteria and had more than one positive laboratory test at the time of diagnosis. All the women were a CL and aβ2GPI positive, and 16 were also LA positive. This latter group (triple positivity) had distinct features and had more frequently experienced previous thromboembolism (OR= 122.5, 95% CI 16–957, p<0.001).They also had an increased rate of late pregnancy loss (OR=16.2, 95%CI 0.9–292, p=0.01), and a higher IgG aβ2GPI titer at diagnosis (median, 25th and 75th percentile were 118, 37–962, vs. 23, 18–32, respectively, p<0.0001). During follow-up, the rate of thromboembolic events was significantly higher in the group of women with triple positivity and/ or previous thromboembolism (OR=57.5, 95% CI 2.7–1160, p=0.0004) which were the only independent predictors of TE in the multivariate model. Recurrent pregnancy loss took place in seven out of 47 women who had a new pregnancy. Triple positivity and/or previous thromboembolism were again the only independent markers (OR=34.4, 95% CI 3.5–335.1, p=0.003) of an unsuccessful new pregnancy. In conclusion, in primary APS with pregnancy morbidity in classification category I, quite different groups of patients may be identified on the basis of laboratory tests. Triple positivity and/or a history of thromboembolism predict new TE events and new unsuccessful pregnancies.

scholarly journals ANTIPHOSPHOLIPID SYNDROME

2017 ◽  
pp. 4-11
Author(s):  
E. V. Makarenko
Keyword(s):  
Blood Plasma ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Lupus Anticoagulant ◽  
Pregnancy Complication ◽  
Classification Criteria ◽  
Clinical Criteria ◽  
Glycoprotein I ◽  
Acquired Thrombophilia

Antiphospholipid syndrome is autoimmune acquired thrombophilia associated with the formation of antibodies to phospholipids, which is manifested by recurrent venous or arterial thrombosis and/or pathology of pregnancy. Antiphospholipid antibodies are a heterogeneous group of autoantibodies interacting with phospholipids, which are components of cell membranes and phospholipid-binding proteins of blood plasma. Antiphospholipid syndrome can affect vessels of any caliber and localization, with thrombosis accompanied by no morphological signs of inflammation in the wall of the vessel. Obstetrical pathology is manifested by loss of the fetus, which can occur at any time of pregnancy, as well as other complications of pregnancy, such as preeclampsia and placental insufficiency. Based on the classification criteria, antiphospholipid syndrome is diagnosed if one of the clinical criteria (thrombosis or pregnancy complication) and one of the laboratory criteria including the lupus anticoagulant, antibodies to cardiolipin or β2-glycoprotein I, are revealed. The main tactic of the treatment of patients with antiphospholipid syndrome is to prevent thrombosis. For this purpose, the traditional therapy with anticoagulants and antiaggregants is applied. In addition, new medicines are being developed and evaluated

scholarly journals Clinical diagnosis in patients with positive antiphospholipid antibodies

2020 ◽  
Vol 105 (105(810)) ◽  
pp. 90-95
Author(s):  
P. Herreros Fernández-Arroyo ◽  
J. M. Urra-Ardanaz
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Thrombotic Event ◽  
Primary Antiphospholipid Syndrome ◽  
Clinical Environment ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Igm Antibodies ◽  
Coagulation Tests

Objective: To know the relationship between the presence of three antiphospholipid antibodies: lupus anticoagulant and the anticardiolipin of isotypes IgM and IgG with the development of thrombotic events and alterations in coagulation and also, study the clinical environment in which those antibodies appear. Material and methods: Cross-sectional descriptive study in which we have analyzed retrospectively, in 123 patients with positive results for at least one of the antiphospholipid antibodies under study, their alterations in coagulation, if they suffer or have suffered any thrombotic event and the clinical environment in which these antibodies appear and. Results: 52,1% of patients with positive lupus anticoagulant have some type of abnormality in coagulation tests, compared with 43,75% of patients with anticardiolipin of isotype IgG and 24,64% of patients with anticardiolipin of isotypes IgM. The most frequent antibody in patients with primary antiphospholipid syndrome is anticardiolipin of isotypes IgM, which appears in 75%, while in the case of patients with secondary antiphospholipid syndrome due to erythematosus systemic lupus, the most frequent antibody is anticardiolipin of isotypes IgG, which is detected in 46,7%. Among the patients who suffered thrombotic event, in 45,94% anticardiolipin of isotypes IgM was detected, compared with 43,24% with lupus anticoagulant, and only 16,22% with anticardiolipin of isotype IgG. Conclusions: The antiphospholipid antibodies that alters coagulation tests to a greater extent is the lupus anticoagulant. Anticardiolipin of isotype IgM antibodies are the most frequent in primary antiphospholipid syndrome while anticardiolipin of isotype IgG are associated in a greater degree with secondary antiphospholipid syndrome, especially in patients with erythematosus systemic lupus. Anticardiolipin of isotype IgM antibodies represent a higher risk of thrombotic events in patients with positive antiphospholipid antibodies.

scholarly journals A brief history of antiphospholipid antibodies and antiphospholipid syndrome

2018 ◽  
Vol 28 (3) ◽  
pp. 31097
Author(s):  
Henrique Luiz Staub ◽  
Lia Portella Staub
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Anticardiolipin Antibody ◽  
Early Years ◽  
Clinical Criteria ◽  
Pregnancy Morbidity ◽  
History Of ◽  
Obstetric Aps ◽  
Definition Of

AIMS: To review the historical reports on antiphospholipid antibodies (aPL) from the early years of the 20th century; to outline the cardinal features of the antiphospholipid syndrome (APS) from 1983 on, including clinical criteria, etiopathogenesis and current therapy.METHODS: Literature review using PubMed. Articles on the history of aPL and APS were selected.RESULTS: The original aPL were described in patients with syphilis yet in 1906 by Wassermann. A first definition of lupus anticoagulant was proposed in 1963,while the anticardiolipin antibody (aCL) test was depicted twenty years later. The APS, initially reported by Hughes in 1985as the “aCL syndrome”, is one of the most prevalent acquired thrombophilia. Venous and arterial thrombosis, associated or not to pregnancy morbidity, comprise the main features. It is a novel disorder firstly associated to systemic lupus erythematosus. A primary form of APS was put forward in 1989, and many APS variants are currently known. Lifelong, full-dose anticoagulation is the mainstream for treatment of thrombotic APS. In obstetric APS, the combination of acetil-salicilic acid and enoxoparin has been a mostly effective therapy.CONCLUSIONS: The sequential characterization of aPL since Wassermann in 1906, and later of the APS in the 1980-thies, is a rather interesting example of how a new entity is sketched step by step. APS is an intriguing novel cause of autoimmune thrombophilia, with a complex pathogenesis and a plethora of clinical and laboratory abnormalities. Treatment is based on life-long anticoagulation. 

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