scholarly journals The antiphospholipid syndrome: still an enigma

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Shruti Chaturvedi ◽  
Keith R. McCrae
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Basic Research ◽  
Laboratory Diagnosis ◽  
Pregnancy Morbidity ◽  
Common Causes

Abstract Antiphospholipid syndrome (APS) is defined by clinical manifestations that include thrombosis and/or fetal loss or pregnancy morbidity in patients with antiphospholipid antibodies (aPL). Antiphospholipid antibodies are among the most common causes of acquired thrombophilia, but unlike most of the genetic thrombophilias are associated with both venous and arterial thrombosis. Despite an abundance of clinical and basic research on aPL, a unified mechanism that explains their prothrombotic activity has not been defined; this may reflect the heterogeneity of aPL and/or the fact that they may influence multiple pro- and/or antithrombotic pathways. Antiphospholipid antibodies are directed primarily toward phospholipid binding proteins rather than phospholipid per se, with the most common antigenic target being β2-glycoprotein 1 (β2GPI) although antibodies against other targets such as prothrombin are well described. Laboratory diagnosis of aPL depends upon the detection of a lupus anticoagulant (LA), which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin and anti-β2-glycoprotein 1 antibodies. Indefinite anticoagulation remains the mainstay of therapy for thrombotic APS, although new strategies that may improve outcomes are emerging. Preliminary reports suggest caution in the use of direct oral anticoagulants in patients with APS-associated thrombosis. Based on somewhat limited evidence, aspirin and low molecular weight heparin are recommended for obstetrical APS. There remains a pressing need for better understanding of the pathogenesis of APS in humans, for identification of clinical and laboratory parameters that define patients at greatest risk for APS-related events, and for targeted treatment of this common yet enigmatic disorder.

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.

Detection of Antiphospholipid Antibodies by Flow Cytometry: Rapid Detection of Antibody Isotype and Phospholipid Specificity

1993 ◽  
Vol 70 (04) ◽  
pp. 603-607 ◽  
Author(s):  
M W Stewart ◽  
W S Etches ◽  
A S Russell ◽  
J S Percy ◽  
C A Johnston ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Fetal Loss ◽  
Laboratory Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Isotype ◽  
Anionic Phospholipids ◽  
Flow Cytometric Method ◽  
Antibody Isotypes

SummaryLaboratory diagnosis of antiphospholipid antibodies is important in patients with clinical features of the antiphospholipid syndrome, such as thrombosis and fetal loss. We have developed a novel method for the detection of antiphospholipid antibodies using flow cytometry. Anionic phospholipids cardiolipin, phosphatidylserine and phosphatidylinositol are coated onto polystyrene beads of different sizes, allowing detection and semiquantitation of their respective phospholipid antibody isotypes. The results of the flow cytometric method closely correlate those of the standardised anticardiolipin enzyme-linked immunosorbent assay (ELISA), but the method is quicker and is versatile in its ability to detect IgG, IgM and IgA antibody isotypes at the same time. The method promises to be useful in evaluating the significance of phospholipid specificity and antibody isotypes in patients with the antiphospholipid syndrome.

Clinical manifestations in patients with antiphospholipid antibodies: Beyond thrombosis and pregnancy loss

Lupus ◽  
2021 ◽  
pp. 096120332199524
Author(s):  
Irene Cecchi ◽  
Massimo Radin ◽  
Elena Rubini ◽  
Silvia G Foddai ◽  
Alice Barinotti ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Clinical Manifestations ◽  
Case Series ◽  
Clinical Spectrum ◽  
Prothrombotic State ◽  
Pregnancy Morbidity ◽  
Immunological Condition

The clinical spectrum of the antiphospholipid syndrome (APS) encompasses additional manifestations other than thrombosis and pregnancy morbidity, which may potentially affect every organ and system. The pathophysiology of APS indeed cannot be explained exclusively by a prothrombotic state and the “extra-criteria” manifestations of the syndrome should be attributed to other mechanisms, such as inflammation, complement and platelet activation. In this case-series, we report patients with uncommon clinical APS presentations, to highlight relevant peculiarities of the syndrome, potentially paving the way for a further update of clinical as well as laboratory manifestations of this complex immunological condition.

scholarly journals The Role of Direct Oral Anticoagulants in Antiphospholipid Syndrome

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3680-3680
Author(s):  
Mohammed Abdullah Alsheef ◽  
Mukhtar Alomar ◽  
Ohoud Alarfaj ◽  
Hussam A AlHamidi ◽  
Abdul Rehman Z. Zaidi
Keyword(s):  
Antiphospholipid Syndrome ◽  
Major Bleeding ◽  
Conflicts Of Interest ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Double Positive ◽  
Unusual Site ◽  
Pregnancy Morbidity ◽  
Single Positive ◽  
Age Range

Background Antiphospholipid Syndrome (APS) is defined by thrombosis and/or pregnancy morbidity in patients with antiphospholipid antibodies (aPL). There remains a pressing need for identification of clinical and laboratory parameters that define patients at most considerable risk for APS-related events on Direct oral anticoagulants (DOACs). Aims To demonstrate the efficacy and safety of DOAC (Rivaroxaban) compared with Warfarin (Vitamin K Antagonist) in patients with thrombotic APS. Methods A retrospective cohort study of thrombotic APS patients who were started on anticoagulant therapy, either VKA or DOAC, from 2010 -2016. Results We investigated 73 patients diagnosed with APS. 83.5% of the patients were female. The age range at diagnosis was between 26-40 (52%). 67% of the cases were diagnosed in the form of DVT while the rest had arterial or unusual site venous thrombosis. 43% of the patients had systemic lupus disease. 28% of the cases had a single-positive aPL profile, 23% had double-positive, and 49% had triple-positive aPL. 68.5% of the cases were treated with warfarin, while 31.5% of the cases were switched from warfarin to Rivaroxaban. 15% of patients had major and clinically relevant non-major bleeding (2 patients had major bleeding in the warfarin group, and four patients in the rivaroxaban group). Recurrence of thrombosis (arterial and venous) was 43% with Rivaroxaban and 30% with warfarin. The average duration from starting Rivaroxaban to development of complications such as bleeding and thromboembolic events was mostly after 1-2 years (70%). Conclusions Rivaroxaban should be used with extreme caution in APS patients, especially patients with a full positive aPL profile and arterial thrombosis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Non-Criteria Manifestations of Juvenile Antiphospholipid Syndrome

2021 ◽  
Vol 10 (6) ◽  
pp. 1240
Author(s):  
Takako Miyamae ◽  
Tomohiro Kawabe
Keyword(s):  
Heart Disease ◽  
Antiphospholipid Syndrome ◽  
Valvular Heart Disease ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Autoimmune Disorder ◽  
Classification Criteria ◽  
Neurologic Manifestations ◽  
Test Results ◽  
Pregnancy Morbidity

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder mainly characterised by increased risks of thrombosis and pregnancy morbidity and persistent positive test results for antiphospholipid antibodies (aPLs). The criteria for diagnosing juvenile APS have yet to be validated, while the Sydney classification criteria do not contain several non-thrombotic clinical manifestations associated with the presence of aPLs. As such, difficulties have been encountered in the diagnosis of patients who have no certain thrombotic occlusions. Moreover, extra-criteria manifestations (i.e., clinical manifestations not listed in the classification criteria), including neurologic manifestations (chorea, myelitis and migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia), livedo reticularis, nephropathy and valvular heart disease have been reported, which suggests that the clinical spectrum of aPL-related manifestations extends beyond that indicated in the classification criteria. Studies have demonstrated that more than 40% of children with aPLs demonstrated non-thrombotic aPL-related clinical manifestations alone. Moreover, our results showed that the pathogenesis of non-criteria manifestations is characterised by “APS vasculopathy”. The present review introduces the characteristics and findings of non-criteria manifestations observed in juvenile APS.

Prevalence of Antiphospholipid Antibodies Negativisation in Patients with Antiphospholipid Syndrome: A Long-Term Follow-Up Multicentre Study

2019 ◽  
Vol 119 (12) ◽  
pp. 1920-1926 ◽  
Author(s):  
Massimo Radin ◽  
Karen Schreiber ◽  
Savino Sciascia ◽  
Dario Roccatello ◽  
Irene Cecchi ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Thrombotic Event ◽  
Clinical Manifestations ◽  
Inclusion Criteria ◽  
Pregnancy Morbidity ◽  
Long Term Follow Up ◽  
Observation Period

Abstract Objective This article aims to analyse the rate of antiphospholipid antibodies (aPL) negativisation in patients with antiphospholipid syndrome (APS), and to evaluate potential new clinical manifestations after negativisation and/or aPL fluctuations in a long-term follow-up. Methods Inclusion criteria are (1) any patients with an APS diagnosis according to the current Sydney criteria and (2) patients in whom aPL negativisation occurred. aPL negativisation was defined as repeated aPL measurements on at least two consecutive occasions at least 12 weeks apart, with a follow-up of at least 1 year since aPL first turned negative. Results Out of 259 APS patients, a total of 23 patients (8.9%) met the inclusion criteria for persistent aPL negativisation. Patients were followed-up for 14.4 ± 8.1 years, experienced aPL negativisation after a mean of 5.3 ± 3.5 years and were followed-up after experiencing the aPL negativisation for a mean of 7.6 ± 5.8 years. Seventeen patients (73.9%) presented with thrombotic APS, 2 with pregnancy morbidity (8.7%) and 4 (17.4%) with both. Most of the patients (18; 78.3%) had a single aPL positivity, 5 (21.7%) double, while no triple aPL positivity was observed. At the time of data collection, after aPL negativisation, anticoagulation was stopped in 8 patients with previous thrombotic venous event (8/21, 38%) according to the treating physicians' judgements. None of the patients experienced any recurrent thrombotic event during the follow-up period after their aPL negativisation. Conclusion In our patient cohort consisting of 259 patients with definitive APS, we observed over a mean observation period of > 5 years, that aPL negativisation occurred in approximately 9% of patients. Negativisation occurred most often in patients who were previously found to be positive for only one aPL.

Current concepts on the pathogenesis of the antiphospholipid syndrome

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 422-430 ◽  
Author(s):  
Bill Giannakopoulos ◽  
Freda Passam ◽  
Soheila Rahgozar ◽  
Steven A. Krilis
Keyword(s):  
Experimental Evidence ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Peripheral Tolerance ◽  
The Core ◽  
Glycoprotein I ◽  
Antigenic Targets ◽  
Acquired Thrombophilia

Abstract The antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia. It is characterized by the core clinical manifestations of thrombosis, either venous or arterial, and in women it can also be associated with recurrent fetal loss. The detection of persistently elevated levels of antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the diagnosis to be made. The dominant antigenic targets in APS are beta 2-glycoprotein I (β2-GPI) and prothrombin. There is an accumulating body of experimental evidence that suggests that specific subgroups of aPL Abs may directly contribute to disease pathogenesis. This review critically examines the experimental evidence underlying the various propositions made to explain how these antibodies may predispose to disease in humans. Furthermore, it also examines the evidence relating to the immunologic mechanisms that may contribute to the breakage of peripheral tolerance in this disorder. Delineating the strengths and limitations of the experimental evidence accumulated thus far will hopefully stimulate further experimentation toward achieving the ultimate goal of precisely defining the dominant pathogenic mechanisms operational in APS. This may pave the way for the development of improved therapies.

scholarly journals Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuela Velásquez ◽  
Luisa F. Peláez ◽  
Mauricio Rojas ◽  
Raúl Narváez-Sánchez ◽  
Jesús A. Velásquez ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Endothelial Activation ◽  
No Production ◽  
Endothelin 1 ◽  
New Therapies ◽  
Pregnancy Morbidity ◽  
Obstetric Aps

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy morbidity or thrombosis and persistent antiphospholipid antibodies (aPL) that bind to the endothelium and induce endothelial activation, which is evidenced by the expression of adhesion molecules and the production of reactive oxygen species (ROS) and subsequent endothelial dysfunction marked by a decrease in the synthesis and release of nitric oxide (NO). These endothelial alterations are the key components for the development of severe pathological processes in APS. Patients with APS can be grouped according to the presence of other autoimmune diseases (secondary APS), thrombosis alone (thrombotic APS), pregnancy morbidity (obstetric APS), and refractoriness to conventional treatment regimens (refractory APS). Typically, patients with severe and refractory obstetric APS exhibit thrombosis and are classified as those having primary or secondary APS. The elucidation of the mechanisms underlying these alterations according to the different groups of patients with APS could help establish new therapies, particularly necessary for severe and refractory cases. Therefore, this study aimed to evaluate the differences in endothelial activation and dysfunction induced by aPL between patients with refractory obstetric APS and other APS clinical manifestations. Human umbilical vein endothelial cells (HUVECs) were stimulated with polyclonal immunoglobulin-G (IgG) from different groups of patients n = 21), including those with primary (VTI) and secondary thrombotic APS (VTII) and refractory primary (RI+), refractory secondary (RII+), and non-refractory primary (NR+) obstetric APS. All of them with thrombosis. The expression of adhesion molecules; the production of ROS, NO, vascular endothelial growth factor (VEGF), and endothelin-1; and the generation of microparticles were used to evaluate endothelial activation and dysfunction. VTI IgG induced the expression of adhesion molecules and the generation of microparticles and VEGF. RI+ IgG induced the expression of adhesion molecules and decreased NO production. RII+ IgG increased the production of microparticles, ROS, and endothelin-1 and reduced NO release. NR+ IgG increased the production of microparticles and endothelin-1 and decreased the production of VEGF and NO. These findings reveal differences in endothelial activation and dysfunction among groups of patients with APS, which should be considered in future studies to evaluate new therapies, especially in refractory cases.

scholarly journals Primary antiphospholipid syndrome in children: experience from two tertiary centres in South India

2019 ◽  
Vol 6 (2) ◽  
pp. 243
Author(s):  
Mahesh Janarthanan ◽  
Dhaarani Jayaraman ◽  
Julius Scott ◽  
M. S. Latha ◽  
Saravanan Margabandhu ◽  
...  
Keyword(s):  
Clinical Features ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Fetal Loss ◽  
Primary Antiphospholipid Syndrome ◽  
Retrospective Case ◽  
Case Record ◽  
Vascular Thrombosis ◽  
Immunologic Profile

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by the presence of episodes of vascular thrombosis, recurrent fetal loss and other clinical features in the presence of antiphospholipid antibodies. The aim of the study was to analyze the clinical manifestations and immunologic profile of children presenting with APS.Methods: Authors did a retrospective case record study of patients admitted with thrombotic events between September 2013 and August 2018 and identified patients with positive antiphospholipid antibodies. Children who had clinical features of active lupus were not included.Results: The clinical and immunologic profile of 7 pediatric patients presenting with APS over 5 years from 2013 to 2018 were analysed. Symptoms secondary to vascular thrombosis were limb swelling, stroke, gangrene of toes and Budd Chiari syndrome.Conclusions:APS though rare should be considered in the differential diagnosis of children presenting with thrombotic events. They need long term anticoagulants to prevent further episodes. 

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.

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