scholarly journals Anti-Phosphatidylserine/Prothrombin Antibodies at Two Points: Correlation With Lupus Anticoagulant and Thrombotic Risk

2021 ◽  
Vol 12 ◽  
Author(s):  
Natalia Egri ◽  
Chelsea Bentow ◽  
Laura Rubio ◽  
Gary L. Norman ◽  
Susana López-Sañudo ◽  
...  
Keyword(s):  
Lupus Anticoagulant ◽  
Clinical Manifestations ◽  
Classification Criteria ◽  
Risk Markers ◽  
Thrombotic Risk ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Pt Complex ◽  
Associated Proteins ◽  
Anti Phospholipid Syndrome

Antibodies to phospholipids (aPL) and associated proteins are a hallmark in the diagnosis of anti-phospholipid syndrome (APS). Those included in the classification criteria are the lupus anticoagulant (LA) and the IgG and IgM isotypes of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (β2GPI) antibodies. Non-classification criteria markers such as autoantibodies that recognize the phosphatidylserine/prothrombin (aPS/PT) complex have been proposed as biomarkers for APS. Studies of aPS/PT antibodies have shown a strong correlation to clinical manifestations and LA. We aimed to study the value and the persistence of aPS/PT IgG and IgM antibodies in a cohort of consecutive patients with clinical suspicion of APS and their utility as thrombotic risk markers. Our study, with 103 patients, demonstrates that persistently positive results for aPS/PT IgG antibodies were significantly associated with APS classification, thrombosis, triple aPL positivity, LA positive result, and the Global APS Score (GAPSS) > than 9 points (p < 0.01, for each condition). On the other hand, no association was seen with pregnancy morbidity (p = 0.56) and SLE (p = 0.07). Persistence of aPS/PT antibodies, defined according to the current laboratory classification criteria, likely improves the diagnosis and clinical assessment of patients with APS.

Anti-phospholipid antibody syndrome

2013 ◽  
pp. 957-968
Author(s):  
Munther A. Khamashta ◽  
Graham R. V. Hughes ◽  
Guillermo Ruiz-Irastorza
Keyword(s):  
Clinical Manifestations ◽  
Obstetric Care ◽  
Recurrent Miscarriages ◽  
Heart Attacks ◽  
Pregnancy Morbidity ◽  
Vein Thrombosis ◽  
Glycoprotein I ◽  
Deep Vein ◽  
Anti Phospholipid Syndrome

The anti-phospholipid syndrome (APS) described almost 30 years ago, is now recognized as a major cause of deep vein thrombosis, stroke, and heart attacks in young people (<45 years of age). It is also the commonest treatable cause of recurrent miscarriages and a major cause of late fetal death. Other clinical manifestations are cardiac valvular disease, livedo reticularis, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, epilepsy, and cognitive impairment. The presence of anti-phospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop the clinical features. Lupus anticoagulant is generally thought to be more strongly associated with the risk of clinical manifestations of APS than anticardiolipin and anti ?2-glycoprotein I antibodies. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Therapy of thrombosis is based on long-term oral anti-coagulation and patients with arterial events should be treated aggressively. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin.

Anti-phospholipid antibody syndrome

2015 ◽  
Author(s):  
Munther A. Khamashta ◽  
Graham R. V. Hughes ◽  
Guillermo Ruiz-Irastorza
Keyword(s):  
Fetal Death ◽  
Clinical Manifestations ◽  
Obstetric Care ◽  
Heart Attacks ◽  
Pregnancy Morbidity ◽  
Vein Thrombosis ◽  
Glycoprotein I ◽  
Deep Vein ◽  
Anti Phospholipid Syndrome

The anti-phospholipid syndrome (APS) described almost 30 years ago, is now recognized as a major cause of deep vein thrombosis, stroke, and heart attacks in young people (<45 years of age). It is also the commonest treatable cause of recurrent miscarriages and a major cause of late fetal death. Other clinical manifestations are cardiac valvular disease, livedo reticularis, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, epilepsy, and cognitive impairment. The presence of anti-phospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop the clinical features. Lupus anticoagulant is generally thought to be more strongly associated with the risk of clinical manifestations of APS than anticardiolipin and anti ?2-glycoprotein I antibodies. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Therapy of thrombosis is based on long-term oral anti-coagulation and patients with arterial events should be treated aggressively. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin.

Anti-phospholipid antibody syndrome

2013 ◽  
Author(s):  
Munther A. Khamashta ◽  
Graham R. V. Hughes ◽  
Guillermo Ruiz-Irastorza
Keyword(s):  
Fetal Death ◽  
Clinical Manifestations ◽  
Obstetric Care ◽  
Heart Attacks ◽  
Pregnancy Morbidity ◽  
Vein Thrombosis ◽  
Glycoprotein I ◽  
Deep Vein ◽  
Anti Phospholipid Syndrome

The anti-phospholipid syndrome (APS) described almost 30 years ago, is now recognized as a major cause of deep vein thrombosis, stroke, and heart attacks in young people (<45 years of age). It is also the commonest treatable cause of recurrent miscarriages and a major cause of late fetal death. Other clinical manifestations are cardiac valvular disease, livedo reticularis, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, epilepsy, and cognitive impairment. The presence of anti-phospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop the clinical features. Lupus anticoagulant is generally thought to be more strongly associated with the risk of clinical manifestations of APS than anticardiolipin and anti ?2-glycoprotein I antibodies. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Therapy of thrombosis is based on long-term oral anti-coagulation and patients with arterial events should be treated aggressively. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin.

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.

Is There an Additional Value in Detecting Anticardiolipin and Anti-β2 glycoprotein I IgA Antibodies in the Antiphospholipid Syndrome?

2020 ◽  
Vol 120 (11) ◽  
pp. 1557-1568
Author(s):  
Walid Chayoua ◽  
Dong-mei Yin ◽  
Hilde Kelchtermans ◽  
Gary W. Moore ◽  
Jean-Christophe Gris ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Immunoglobulin A ◽  
Clinical Manifestations ◽  
Pregnancy Morbidity ◽  
Medical Centers ◽  
Glycoprotein I ◽  
Iga Antibodies ◽  
Obstetric Aps ◽  
Current Criterion ◽  
Additional Value

Abstract Background Anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) immunoglobulin A (IgA) antiphospholipid antibodies (aPL) have shown to associate with thrombosis and pregnancy morbidity. However, inclusion of IgA aPL in the classification criteria of the antiphospholipid syndrome (APS) has been debated. We investigated the value of aCL and aβ2GPI IgA aPL in the detection of thrombosis and pregnancy morbidity in addition to the current aPL panel for APS. Methods We included 1,068 patients from eight European medical centers: 259 thrombotic APS patients, 122 obstetric APS patients, 204 non-APS thrombosis patients, 33 non-APS obstetric patients, 60 APS patients with unspecified clinical manifestations, 196 patients with autoimmune diseases, and 194 controls. aCL and aβ2GPI IgG/M/A were detected with four commercial assays and lupus anticoagulant was determined by the local center. Results Positivity for IgA aPL was found in 17 to 26% of the patients with clinical manifestations of APS and in 6 to 13% of the control population. Both aCL and aβ2GPI IgA were significantly associated with thrombosis and pregnancy morbidity. Isolated IgA positivity was rare in patients with clinical manifestations of APS (0.3–5%) and not associated with thrombosis and/or pregnancy morbidity. Addition of IgA to the current criterion panel did not increase odds ratios for thrombosis nor pregnancy morbidity. Conclusion aCL and aβ2GPI IgA are associated with clinical manifestations of APS. However, isolated IgA positivity was rare and not associated with thrombosis or pregnancy morbidity. These data do not support testing for aCL and aβ2GPI IgA subsequent to conventional aPL assays in identifying patients with thrombosis or pregnancy morbidity.

Pathophysiological insights into the antiphospholipid syndrome

2017 ◽  
Vol 37 (03) ◽  
pp. 202-207 ◽  
Author(s):  
Davit Manukyan ◽  
Nadine Müller-Calleja ◽  
Karl Lackner
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Manifestations ◽  
Future Research ◽  
Scientific Debate ◽  
Pregnancy Morbidity ◽  
Anionic Phospholipids ◽  
The Third ◽  
Glycoprotein I ◽  
Underlying Mechanisms

SummaryThe antiphospholipid syndrome (APS) is characterized by venous and/or arterial thrombosis and severe pregnancy morbidity in presence of antiphospholipid antibodies (aPL). While there is compelling evidence that aPL cause the clinical manifestations of APS, the underlying mechanisms are still a matter of scientific debate. This is mainly related to the broad heterogeneity of aPL. There are three major types of aPL: The first one binds to (anionic) phospholipids, e.g. cardiolipin, in absence of other factors (cofactor independent aPL). The second type binds to phospholipids only in presence of protein cofactors, e.g. ß2-glycoprotein I (ß2GPI) (cofactor dependent aPL). The third type binds to cofactor proteins directly without need for phospholipids. It is widely believed that cofactor independent aPL (type 1) are associated with infections and, more importantly, non-pathogenic, while pathogenic aPL belong to the second and in particular to the third type. This view, in particular with regard to type 1 aPL, has not been undisputed and novel research data have shown that it is in fact untenable. We summarize the available data on the pathogenetic role of aPL and the implications for diagnosis of APS and future research.

Antiphospholipid-associated thrombocytopenia or autoimmune hemolytic anemia in patients with or without definite primary antiphospholipid syndrome according to the Sapporo revised classification criteria: a 6-year follow-up study

Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 3058-3063 ◽  
Author(s):  
Lucía Comellas-Kirkerup ◽  
Gabriela Hernández-Molina ◽  
Antonio R. Cabral
Keyword(s):  
Hemolytic Anemia ◽  
Antiphospholipid Syndrome ◽  
Autoimmune Hemolytic Anemia ◽  
Lupus Anticoagulant ◽  
Thrombotic Event ◽  
Classification Criteria ◽  
Response To Treatment ◽  
Primary Antiphospholipid Syndrome ◽  
Pregnancy Morbidity

Abstract The updated Sapporo classification criteria for antiphospholipid syndrome (APS) only include thrombosis or pregnancy morbidity as clinical criteria. To test this notion, we studied 55 patients (80% women) with hematologic manifestations. All fulfilled the laboratory criteria for primary APS. Thirty-five patients (64%) had thrombocytopenia, 14 (25%) had autoimmune hemolytic anemia, and 6 (11%) had both. Twenty-five patients (22 women, 88%) also fulfilled one clinical criterion for APS after a median follow-up of 13.2 years (range, 1.45-37 years), whereas the remaining 30 patients (22 women, 73%) have not had any thrombotic event nor pregnancy morbidity after a median follow-up of 5.4 years (range, 0.12-24 years). No patient developed systemic lupus erythematosus during follow-up. The hematologic manifestation was asynchronous with the APS onset in 84% of patients. The response to treatment was similar regardless of the APS status. Patients with definite APS were more frequently positive for the lupus anticoagulant (63%) than lupus anticoagulant-positive patients without APS (30%; odds ratio, 3.5; 95% confidence interval, 1.07-11.4; P < .02). Anticardiolipin or anti–β2-glycoprotein-I antibodies were highly prevalent among the study groups. Our study suggests that, depending upon their antiphospholipid profile, patients with hemocytopenias appear to comprise a peculiar subset of patients with APS; some develop thrombotic and/or obstetric APS whereas others continue with hematologic APS.

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.

Antigenic Specificities of Antiphospholipid Autoantibodies: Implications for Clinical Laboratory Testing and Diagnosis of the Antiphospholipid Syndrome

Lupus ◽  
1996 ◽  
Vol 5 (5) ◽  
pp. 425-430 ◽  
Author(s):  
RAS Roubey
Keyword(s):  
Clinical Studies ◽  
Lupus Anticoagulant ◽  
Laboratory Testing ◽  
Clinical Laboratory ◽  
Clinical Manifestations ◽  
Anticardiolipin Antibodies ◽  
Protein Antigens ◽  
Advantages And Disadvantages ◽  
Glycoprotein I ◽  
Clinical Laboratory Testing

Most autoantibodies associated with the antiphospholipid (aPL) syndrome and detected in standard anticardiolipin and/or lupus anticoagulant assays are directed against β2-glycoprotein I (β2-GPI) or prothrombin. Recent data indicate that these antibodies can also be detected in immunoassays utilizing purified protein antigens, in the absence of phospholipids. Initial clinical studies suggest that positivity in anti-β2-GPI immunoassays is more closely associated with the clinical manifestations of the aPL syndrome than is positivity in conventional anticardiolipin ELISAs. Anti-β2-GPI immunoassays may detect certain anti-β2-GPI antibodies that are not detectable in conventional anticardiolipin assays, but do not detect authentic (β2-GPI-independent) anticardiolipin antibodies. It appears that the former, but not the latter, antibodies are associated with the clinical manifestations of the aPL syndrome. The potential advantages and disadvantages of these new immunoassays in the clinical evaluation of the aPL syndrome are discussed.

Increased Prevalence of Anti-CD36 and Elevated Endothelial Microparticles in Patients with Recurrent Thrombosis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1632-1632
Author(s):  
Carlos J. Bidot ◽  
Wenche Jy ◽  
Camile Ortega ◽  
Larry L. Horstman ◽  
Carlos Bidot ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Activation ◽  
Lupus Anticoagulant ◽  
Clinical Laboratory ◽  
Test Methods ◽  
Recurrent Thrombosis ◽  
Antiplatelet Antibody ◽  
Transmembrane Glycoprotein ◽  
Glycoprotein I ◽  
Anti Phospholipid Syndrome

Abstract BACKGROUND: CD36 is a widely distributed transmembrane glycoprotein, called GpIV on platelets, involved in various physiologic processes. It has been implicated in thrombogenic pathologies such as diabetes, atherosclerosis and anti-phospholipid syndrome (APS). It is also an adhesion molecule capable of interacting with collagens and is considered a platelet collagen receptor. We investigated autoantibodies (Ab) against CD36 in TTP [Schultz et al, BrJH 103:849, 1998]. The present study was undertaken to explore relationships of anti-platelet Ab (aPlt-Ab), antiphospholipid Ab (APLA), and circulating cell-derived microparticles (MP) in patients with thrombosis. METHODS: Forty-five patients with documented thrombosis (TB) referred for hypercoagulable workups were recruited consecutively. Of them, 18 suffered from recurrent thrombosis (rTB) while 27 had a single event (sTB) within the past 5 years. We measured APLA, lupus anticoagulant (LA), antiplatelet antibody (aPlt-Ab) and MP. The APLA were IgG and IgM against cardiolipin (CL) and β2-glycoprotein-I (β2GP1) measured by ELISA. The aPlt-Abs were IgG and IgM reacting to GpIIb/IIIa (CD41b), GpIb/IX (CD42b), and GpIV (CD36), assayed by the PAICA method of Macchi et al [Thromb Haemost 76:1020, 1996]. The following types of MP were measured by flow cytometry: endothelial MP defined by CD31+/CD42− (EMP31) or by CD62E+ (EMP62); platelet MP defined by CD31+/CD42+ (PMP); leukocyte MP defined by CD45+ (LMP); and red blood cell MP by glycophorin+ (RMP). Lupus anticoagulant (LA) was measured in the hospital clinical laboratory and was considered positive if 2 of 3 different test methods were positive. Platelet activation was measured by CD62p expression in flow cytometry. RESULTS: Although both groups had increased prevalence of APLA and LA, there were no significant differences between the sTB and rTB groups. About 70% of patients in both groups were positive for at least one APLA. Of the aPlt-Ab, only aGpIV (aCD36) statistically discriminated between the groups, being more frequent in rTB for both IgG (p&lt;0.02) and IgM (p&lt;0.02). Among the MPs assayed, PMP were elevated in all patients in both groups. EMP62 discriminated best between rTB and sTB (p=0.003). LMP and RMP were also significantly higher in rTB than sTB, p&lt;0.025. When we compared patients CD36+ vs CD36− we found that EMP62 was more frequently elevated in CD36+ patients (7/12, 58%) than in CD36− patients (2/32, 6%), p=0.001. Platelet activation marker CD62p was more often increased in rTB than sTB, p=0.022. CONCLUSION: GpIV (CD36) antibodies are the most prominent risk factor for rTB to emerge from this study. This confirms a previous report [Pelegri et al, Clin Exp Rheum 21:221, 2003]. EMP, LMP, RMP and platelet activation (CD62p) are also increased in the recurrent TB group vs single TB. EMP62 were associated with aCD36. Since CD36 is found also on endothelial cells, this suggests that aCD36 could be responsible for the high EMP62 in the rTB group. The present study demonstrates an association between high EMP62 and aCD36. We suggest that persisting autoantibodies against GpIV activate EC to predispose to recurrent thrombosis.

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