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.

scholarly journals Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gunay Uludag ◽  
Neil Onghanseng ◽  
Anh N. T. Tran ◽  
Muhammad Hassan ◽  
Muhammad Sohail Halim ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Clinical Manifestations ◽  
Autoimmune Disorder ◽  
Ocular Involvement ◽  
Ocular Manifestations ◽  
Different Types ◽  
Thrombotic Complications ◽  
Specific Factors ◽  
Arteries And Veins

AbstractAntiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

Antiphospholipid Syndrome: A Review

2018 ◽  
Vol 2 (02) ◽  
pp. 51-58
Author(s):  
Md. Motahar Hossain ◽  
Md. Akhter Hossain ◽  
Yasmin Rahman ◽  
Md. Kamrul Hasan
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Anticardiolipin Antibodies ◽  
Vitamin K Antagonist ◽  
Classification Criteria ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Pregnancy Morbidity ◽  
Pregnancy And Postpartum

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by venous thromboembolism, arterial thrombosis, and obstetric morbidities in the setting of persistently positive levels of antiphospholipid antibodies. It may be primary or secondary. The latest classification criteria (Sydney 2006) recognize just three tests to define this syndrome- lupus anticoagulant, anticardiolipin antibodies and anti-?2-glycoprotein-1 antibodies. Treatment of thrombotic events involves lifelong anticoagulation with vitamin K antagonist warfarin. Antiphospholipid antibody syndrome (APS) with only pregnancy morbidity is treated with thromboprophylaxis with heparin during pregnancy and postpartum for 6 weeks. In this review we discuss the pathogenesis, diagnosis, treatment and prognosis of the APS.

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.

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.

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.

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 Antiphospholipid syndrome: a case report with an unusual wide spectrum of clinical manifestations

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Carmela Mazzoccoli ◽  
Domenico Comitangelo ◽  
Alessia D’Introno ◽  
Valeria Mastropierro ◽  
Carlo Sabbà ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Symptoms ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Classification Criteria ◽  
Inflammation Markers ◽  
Case Presentation ◽  
Pregnancy Morbidity ◽  
Generalized Seizures ◽  
Laboratory Examinations

Abstract Background Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis, and the detection of circulating antiphospholipid antibodies. The classification criteria for definite APS are actually met when at least one clinical criterion (thrombosis or pregnancy morbidity) is present in association of one laboratory criterion (LAC, aCL antibody or aβ2GPI antibody present on two or more occasions, at least 12 weeks a part), and thrombosis should be confirmed by objective validated criteria. The average age of primary APS patients has been reported to be about 35–40 years and the disease is more common in women than in men. Case presentation In this report, we described a rare case of an adult male who presented over a period of 9 years with a wide spectrum of clinical manifestations involving different organs that were not initially diagnosed as APS. Dizziness and syncope were his first clinical symptoms, and a non-bacterial thrombotic endocarditis (NBTE) involving the mitral valve was at first diagnosed. Subsequently, the patient also presented with generalized seizures and subsequent head injury. When the patient was admitted to our clinic with bilateral epistaxis and fever, thrombocytopenia was revealed. Moreover, laboratory examinations showed acute pancreatitis with an increase of levels of inflammation markers. Conclusion Based on the patient’s medical history and all the examination results, it was possible to make a diagnosis of primary APS and, starting from diagnosis of thrombocytopenia, we were allowed to conclude that all of manifestation were epi-phenomena of a unique clinical entity, rather than unrelated diseases. Though APS is one of the most common thrombocytophilias, unfortunately, it is not recognized often enough. The lack of prevention in undiagnosed patients may cause severe complications which can in turn result in the death of those patients.

Antiphospholipid syndrome

2010 ◽  
Vol 30 (03) ◽  
pp. 139-143 ◽  
Author(s):  
G. M. A. van Os ◽  
R. T. Urbanus ◽  
C. Agar ◽  
J. C. M. Meijers ◽  
P. G. de Groot
Keyword(s):  
Antiphospholipid Syndrome ◽  
Solid Phase ◽  
Clinical Manifestations ◽  
Consensus Meeting ◽  
Classification Criteria ◽  
International Consensus ◽  
Pregnancy Morbidity ◽  
Antibody Assays ◽  
Long Time ◽  
Antibody Elisa

SummaryThe antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL) in the plasma of patients with vascular thrombosis, recurrent complications of pregnancy, or both (1, 2). The presence of aPL in plasma of patients can be detected with either a prolongation of phospholipid dependent coagulation tests (lupus anticoagulant, LAC), or with solid phase immune assays against the protein β2-glycoprotein I (β2-GPI) or the phospholipid cardiolipin (anti-β2-GPI antibody ELISA and anti-cardiolipin antibody ELISA, respectively) (3). For a long time there was a lot of confusion on who had the syndrome and who not. To solve this dispute, an international consensus meeting was organized in Sapporo in 1999 to formulate classification criteria for patients with the antiphospholipid syndrome (4). These criteria have been updated in 2004 at another international consensus meeting in Sydney (5). The classification criteria were defined for scientific purposes and were aimed to be used as inclusion criteria in patient related studies. They were specifically not defined for diagnostic purposes. However, current practice is that these criteria are used as a diagnostic tool. This is very unfortunate because the specificity of the different aPL assays to detect the clinical manifestations that characterize APS are disputable. One of the aims of defining the criteria was to initiate studies to determine the value of the different anti-phospholipid antibody assays to serve as biomarker for the risk of thrombosis and pregnancy morbidity. The recent progress made on this important topic will be discussed.

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 POS0712 “EXTRA”- CRITERIA ANTIPHOSPHOLIPID ANTIBODIES IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOSUS (PRELIMINARY DATA)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 605.2-606
Author(s):  
F. Cheldieva ◽  
T. Reshetnyak ◽  
M. Cherkasova ◽  
N. Seredavkina ◽  
A. Lila
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Preliminary Data ◽  
Antiphospholipid Antibodies ◽  
Disease Duration ◽  
Past History ◽  
Igg Antibodies ◽  
Systemic Lupus ◽  
Pregnancy Morbidity

Background:The study of antiphospholipid antibodies (aPL), not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood.Objectives:To determine the frequency of detection of IgA-aCL and IgA-aβ2GP1 and IgG antibodies to β2GP1 domain 1 (IgG-aβ2GP1-D1) in patients with APS with and without SLE.Methods:ELISA and chemiluminescence assays (CMA) were used to test 63 sera of patients: 22 (35%) with primary APS (pAPS) and 41 (65%) patients with APS and with SLE (secondary APS (sAPS)), with mean age 38,0 [33,0 – 43,0] years and disease duration 4,0 [0,1 – 9,9]. Both methods were used to test of IgG/IgM-aCL and IgG/IgM-aβ2GP1. CMA was used for research IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GPI and IgG-aβ2GP1-D1. Of them 49 (78%) (18 – with pAPS; 31 – with sAPS) displayed major thrombotic events and 18 of 22 pregnant women had pregnancy morbidity in past history. Lupus anticoagulant (LA) positivity was in 9 out of 12 patients who had it determined. LA was not investigated due to anticoagulant therapy in the remaining 52 patients.Results:IgG/IgM-aCL and IgG/IgM-aß2GP1 were recorded in 44/18 and 50/17 patients by ELISA and in 55/19 and 59/16 by CMA, respectively.IgA-aCL positivity was found in 35 (56%) of 63 patients. Thirty IgA-positive patients were positive for IgG-aCL by ELISA: 22 – IgG-aCL – highly positive, 6 – medium positive and 2 – low positive patients. IgM-aCL by ELISA was detected in 13 (37%) of 35 IgA-aCL positive patients: 11 – highly positive, 1 – medium positive and 1 – low positive. IgA-aCL was combined with IgG-aCL in 34 patients and with IgM-aCL in 16 patients in the CMA. IgG-aß2GP1 in ELISA was detected in 32 patients with IgA-aCL (24 –highly positive, 5 – medium positive and 3 – low positive) and in 34 – in CMA. IgM-aß2GP1 was combined with IgA-aß2GP1 with the same frequency in both methods (in 13 patients).IgA-aß2GP1 was detected in 30 (48%) of 63 patients. They were combined with both IgG-aCL and IgG-aß2GP1 in all cases in both methods. IgM-aCL and IgM-aß2GP1 were detected in 14 and 11 of 30 patients with IgA-aß2GP1, respectively. The combination of IgA-aß2GP1 with IgG-aCL by ELISA was in 27 (in most cases highly positive – 20) and with IgM-aCL – in 10 (highly positive - 8). IgG-aß2GP1 was detected in 28 patients with IgA-aß2GP1 (high positive – 21) and in 11 patients with IgM-aß2GP1 (high positive –7).IgG-aß2GP1-D1 was revealed in 48 (76%) patients. It was combined with IgG-aCL – in 38, with IgM-aCL – in 15 patients by the ELISA. The combination of IgG-aß2GP1-D1 by CMA was as follows: with IgG-aCL – in 46, with IgM-aCL – in 17, and with IgA-aCL – in 33 patients. In most cases, IgG-aß2gp1-D1 was combined with highly positive aCL levels. IgG-aß2GP1-D1 positivity was associated with IgG-aß2GP1 positivity in 42 – by ELISA and 47 – by CMA, IgМ-aβ2GP1 – in 13 and 14 patients by ELISA and CMA, respectively, and IgA-aß2GP1 – in 29. Isolated IgG-aß2GP1-D1 positivity was not observed.Conclusion:The frequency of IgA-aCL detection was 56% (35 patients out of 63), IgA-aβ2GP1 – 48% (30 patients out of 63), IgG-aβ2GP1-D1 – 76% (48 patients out of 63). There was not isolated positivity of this “extra” criterial antibodies. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with highly positivity of IgG/IgM-aCL and IgG/IgM- aβ2GP1.Disclosure of Interests:None declared

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