scholarly journals Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management—An Insight into Future Approaches

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Cecilia Beatrice Chighizola ◽  
Tania Ubiali ◽  
Pier Luigi Meroni
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Manifestations ◽  
Controversial Issues ◽  
Current Management ◽  
Pharmacological Agents ◽  
Future Studies ◽  
Clinical Criteria ◽  
Pregnancy Morbidity ◽  
The Impact ◽  
Insight Into

Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS), which is serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control.

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.

Pregnancy Morbidity in Antiphospholipid Syndrome: What Is the Impact of Treatment?

2014 ◽  
Vol 16 (2) ◽  
Author(s):  
Guilherme R. de Jesús ◽  
Gustavo Rodrigues ◽  
Nilson R. de Jesús ◽  
Roger A. Levy
Keyword(s):  
Antiphospholipid Syndrome ◽  
Pregnancy Morbidity ◽  
The Impact

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.

Temporal complexity in clinical manifestations of lung disease

2011 ◽  
Vol 110 (6) ◽  
pp. 1723-1731 ◽  
Author(s):  
Urs Frey ◽  
Geoffrey Maksym ◽  
Béla Suki
Keyword(s):  
Lung Function ◽  
Statistical Physics ◽  
Clinical Manifestations ◽  
Individual Risk ◽  
Fluctuation Analysis ◽  
Temporal Complexity ◽  
History Of ◽  
The Individual ◽  
The Impact ◽  
Insight Into

In this review, we summarize results of recent research on the temporal variability of lung function, symptoms, and inflammatory biomarkers. Specifically, we demonstrate how fluctuation analysis borrowed from statistical physics can be used to gain insight into neurorespiratory control and complex chronic dynamic diseases such as asthma viewed as a system of interacting components (e.g., inflammatory, immunological, and mechanical). Fluctuation analysis tools are based on quantifying the distribution and the short- and long-term temporal history of tidal breathing and lung function parameters to assess neurorespiratory control and monitor chronic disease. The latter includes the assessment of severity and disease control, the impact of treatment and environmental triggers, the temporal characterization of disease phenotypes, and the individual risk of exacerbation. While in many cases specific mechanistic insight into the fluctuations still awaits further research, appropriate analyses of the fluctuations already impact on clinical science and practice.

Morbidity, Mortality, and Organ Damage in Patients with Antiphospholipid Syndrome

2012 ◽  
Vol 39 (3) ◽  
pp. 516-523 ◽  
Author(s):  
ELEFTHERIA P. GRIKA ◽  
PANAYIOTIS D. ZIAKAS ◽  
ELIAS ZINTZARAS ◽  
HARALAMPOS M. MOUTSOPOULOS ◽  
PANAYIOTIS G. VLACHOYIANNOPOULOS
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Descriptive Analysis ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Pregnancy Morbidity ◽  
Initial Event ◽  
Unit Increase

Objective.To describe morbidity, organ damage, mortality, and cause of death in patients with antiphospholipid syndrome (APS).Methods.Descriptive analysis of 135 patients. Patients were clustered according to initial event: arterial thrombosis including stroke (AT; n = 46), venous thrombosis including pulmonary emboli (VT; n = 53), or pregnancy morbidity (PM; n = 36). Disease progression according to initial event and prevalence of organ damage was observed.Results.APS occurs among young individuals (mean age 33.3 ± 11.9 yrs). One-third of the patients have APS secondary to systemic lupus erythematosus (SLE) or SLE-like disease. A broad spectrum of clinical manifestations mark the disease onset even before diagnosis. The pattern of initial presentation is preserved with regard to second event; VT is followed by VT (84%), AT is followed by AT (95%), and PM is followed by PM (88.9%). The highest morbidity is attributed to neurologic damage. PM is more likely to be followed by a second event, yet is associated with less organ damage than AT and VT. After a mean followup of 7.55 years, 29% of patients experienced organ damage and 5 died, with Systemic Lupus International Collaborating Clinics score associated with increased mortality (HR 1.31, 95% CI 1.07–1.60, p = 0.01, per 1-unit increase); hematological malignancies occurred in 2 patients after a cumulative followup of 1020 person-years. Coexistent SLE adds significant damage in patients with APS.Conclusion.APS is a disease of young individuals, who experience increased morbidity. Neurologic damage is the most common cause of morbidity. AT at presentation as well as coexistent SLE are associated with poor outcome.

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.

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.

scholarly journals A Study on Managers' Creation of Budgetary Slack in Emerging Economies: The Case of Vietnam

2017 ◽  
Vol 2 (2) ◽  
pp. 15-28
Author(s):  
Quang-Huy Ngo ◽  
Thi-Nam-Ninh Doan ◽  
Thanh-Nha Huynh
Keyword(s):  
Information Asymmetry ◽  
Emerging Economies ◽  
The Other ◽  
Budgetary Slack ◽  
Future Studies ◽  
Developed Economies ◽  
Budgetary Participation ◽  
The Creation ◽  
The Impact ◽  
Insight Into

Although the budgeting literature well documents managers' creation of budgetary slack in developed economies, lack of attention has been paid to this behaviour in emerging economies. It is doubtful that some unique characteristics, only existing in emerging economies, cause this behaviour to be different than the budgeting literature predicts. Since there is no study examining managers' creation of budgetary slack in emerging economies, such as Vietnam, to get insight into whether or not these characteristics cause the differences, the aim of this study is to replicate prior budgeting studies by using Vietnamese samples. Particularly, we investigated the impact of budgetary participation, budget emphasis, information asymmetry, and the interactions between these variables on managers' creation of budgetary slack. Data obtained from the questionnaire sent to 99 Vietnamese managers shows that the last two variables and the interaction between them induce managers' creation of budgetary slack. However, the results also indicate that the first variable and the interaction between this variable and the other two variables respectively have no impact on managers' creation of budgetary slack. These results provide some insight into the creation of budgetary slack of Vietnamese managers for future studies to extend the line of research.

Diplomacy and Intelligence

2017 ◽  
Author(s):  
John D. Stempel
Keyword(s):  
Policy Making ◽  
The Political ◽  
Strategic Interactions ◽  
Intelligence Gathering ◽  
Future Studies ◽  
Ongoing Work ◽  
Creative Tension ◽  
The Impact ◽  
Descriptive Level ◽  
Insight Into

There is a potentially serious difference between diplomacy and intelligence. Creative tension between diplomacy and intelligence stems from the involvement of both with questions of strategy and statecraft. Indeed, the source of this conflict is often clandestine or covert activities that become public and adversely affect both relations between states and diplomats’ ongoing work. Early works in the intelligence scholarship focuses basically at the descriptive level and centers on acquiring information. In 1922, studies began considering the political aspects of the intelligence–diplomacy connection, zeroing in on the defects of US intelligence and the adequacy of policies, including those related to intelligence gathering and its impact on diplomacy. Studies about the details of the intelligence–diplomacy connection also began to appear. These studies look at the interplay between intelligence and policy making as well as the morality of clandestine operations. In order to link intelligence goals to policy needs, future studies on the intelligence–diplomacy connection should further assess the impact of culture on intelligence gathering and perception, provide better insight into the characteristics of good versus bad intelligence officers and diplomats, include qualitative estimates of the effectiveness and efficacy of techniques and strategies as well as legal and ethical discussions of control and policy, and explore the strategic interactions between intelligence officers and diplomats and how these are managed in various governing systems.

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