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Translational Research : the Journal of... Nov 2020Antiphospholipid syndrome is one of the more common acquired causes of hypercoagulability. Its major presentations are thrombotic (arterial, venous, or microvascular)... (Review)
Review
Antiphospholipid syndrome is one of the more common acquired causes of hypercoagulability. Its major presentations are thrombotic (arterial, venous, or microvascular) and pregnancy morbidity (miscarriages, late intrauterine fetal demise, and severe pre-eclampsia). Classification criteria include 3 different antiphospholipid antibodies: lupus anticoagulant, anticardiolipin, and anti-beta 2 glycoprotein I. Management includes both preventive strategies (low-dose aspirin, hydroxychloroquine) and long-term anticoagulation after thrombosis.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Humans
PubMed: 32413497
DOI: 10.1016/j.trsl.2020.04.006 -
Current Opinion in Rheumatology May 2023Antiphospholipid syndrome (APS) is an acquired thrombo-inflammatory disease that has morbid and sometimes devastating effects on patients and their families. This review... (Review)
Review
PURPOSE OF REVIEW
Antiphospholipid syndrome (APS) is an acquired thrombo-inflammatory disease that has morbid and sometimes devastating effects on patients and their families. This review will discuss the most recent international societal treatment guidelines and propose practical management algorithms for various APS sub-types.
RECENT FINDINGS
APS represents a disease spectrum. Although thrombosis and pregnancy morbidities are traditional hallmarks of APS, a variety of extra-criteria clinical phenotypes can often be seen, which makes clinical management more challenging. Primary APS thrombosis prophylaxis should take a risk-stratified approach. Although vitamin K antagonists (VKAs) or heparin/low molecular weight heparin (LMWH) remain the preferred treatment for secondary APS thrombosis prophylaxis, some international society guidelines support the use of direct oral anticoagulants (DOACs) in certain circumstances. Careful monitoring and individualized obstetric care with the use of aspirin and heparin/LMWH will improve pregnancy outcomes among pregnant individuals with APS. Treatment of microvascular and catastrophic APS remains challenging. While the addition of various immunosuppressive agents is often utilized, further systemic evaluations of their use are warranted before definitive recommendations can be made. Several new therapeutic strategies are on the horizon that might enable more personalized and targeted APS management in the near future.
SUMMARY
Although the knowledge of APS pathogenesis has grown in recent years, the management principles and strategies are largely unchanged. There is an unmet need for evaluating pharmacological agents, beyond anticoagulants, that target diverse thromboinflammatory pathways.
Topics: Pregnancy; Female; Humans; Antiphospholipid Syndrome; Heparin, Low-Molecular-Weight; Anticoagulants; Aspirin; Thrombosis
PubMed: 36866678
DOI: 10.1097/BOR.0000000000000932 -
Blood Reviews Nov 2017Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (APLA).... (Review)
Review
Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (APLA). Laboratory diagnosis of APLA depends upon the detection of a lupus anticoagulant, which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin (aCL) and anti-β2-glycoprotein-1 (β2GPI) antibodies. APLA are primarily directed toward phospholipid binding proteins. Pathophysiologic mechanisms underlying thrombosis and pregnancy loss in APS include APLA induced cellular activation, inhibition of natural anticoagulant and fibrinolytic systems, and complement activation, among others. There is a high rate of recurrent thrombosis in APS, especially in triple positive patients (patients with lupus anticoagulant, aCL and anti-β2GPI antibodies), and indefinite anticoagulation with a vitamin K antagonist is the standard of care for thrombotic APS. There is currently insufficient evidence to recommend the routine use of direct oral anticoagulants (DOAC) in thrombotic APS. Aspirin with low molecular weight or unfractionated heparin may reduce the incidence of pregnancy loss in obstetric APS. Recent insights into the pathogenesis of APS have led to the identification of new potential therapeutic interventions, including anti-inflammatory and immunomodulatory therapies. Additional research is needed to better understand the effects of APLA on activation of signaling pathways in vascular cells, to identify more predictive biomarkers that define patients at greatest risk for a first or recurrent APLA-related clinical event, and to determine the safety and efficacy of DOACs and novel anti-inflammatory and immune-modulatory therapies for refractory APS.
Topics: Animals; Anti-Inflammatory Agents; Anticoagulants; Antiphospholipid Syndrome; Disease Management; Enzyme Inhibitors; Female; Humans; Hydroxychloroquine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pregnancy; Pregnancy Complications; Signal Transduction; Thrombosis
PubMed: 28784423
DOI: 10.1016/j.blre.2017.07.006 -
Seminars in Immunopathology May 2022Antiphospholipid syndrome (APS) is an autoimmune thrombophilia propelled by circulating antiphospholipid antibodies that herald vascular thrombosis and obstetrical... (Review)
Review
Antiphospholipid syndrome (APS) is an autoimmune thrombophilia propelled by circulating antiphospholipid antibodies that herald vascular thrombosis and obstetrical complications. Antiphospholipid antibodies recognize phospholipids and phospholipid-binding proteins and are not only markers of disease but also key drivers of APS pathophysiology. Thrombotic events in APS can be attributed to various conspirators including activated endothelial cells, platelets, and myeloid-lineage cells, as well as derangements in coagulation and fibrinolytic systems. Furthermore, recent work has especially highlighted the role of neutrophil extracellular traps (NETs) and the complement system in APS thrombosis. Beyond acute thrombosis, patients with APS can also develop an occlusive vasculopathy, a long-term consequence of APS characterized by cell proliferation and infiltration that progressively expands the intima and leads to organ damage. This review will highlight known pathogenic factors in APS and will also briefly discuss similarities between APS and the thrombophilic coagulopathy of COVID-19.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; COVID-19; Endothelial Cells; Humans; Thromboinflammation; Thrombosis; Vascular Diseases
PubMed: 35122116
DOI: 10.1007/s00281-022-00916-w -
Frontiers in Immunology 2019
Topics: Antiphospholipid Syndrome; Diagnosis, Differential; Disease Susceptibility; Humans; Lupus Erythematosus, Systemic
PubMed: 30858846
DOI: 10.3389/fimmu.2019.00199 -
Thrombosis Research Feb 2021Thrombotic antiphospholipid syndrome (APS) is characterised by venous, arterial and/or small vessel thrombosis in the context of persistently positive antiphospholipid... (Review)
Review
Thrombotic antiphospholipid syndrome (APS) is characterised by venous, arterial and/or small vessel thrombosis in the context of persistently positive antiphospholipid antibodies (aPL). The diagnosis and management of thrombotic APS continues to prove challenging for clinicians. We provide a practical guide to the diagnosis of APS including who to test for aPL and which tests to do. We also consider clinical practice points on the management of venous, arterial and small vessel thrombosis, in the context of first and recurrent thrombotic events. Non-criteria manifestations of APS are reviewed. An approach to recurrent thrombosis and anticoagulant-refractory APS is discussed, with options including increasing the anticoagulation intensity of vitamin K antagonists, switching to low-molecular-weight-heparin, the use of fondaparinux and/or the addition of antiplatelet treatment. Adjunctive options such as vitamin D, hydroxychloroquine and statins are also addressed.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Humans; Thrombosis
PubMed: 33485122
DOI: 10.1016/j.thromres.2020.10.010 -
International Journal of Molecular... Jan 2024Unlike classic APS, CAPS causes multiple microthrombosis due to an increased inflammatory response, known as a "thrombotic storm". CAPS typically develops after... (Review)
Review
Unlike classic APS, CAPS causes multiple microthrombosis due to an increased inflammatory response, known as a "thrombotic storm". CAPS typically develops after infection, trauma, or surgery and begins with the following symptoms: fever, thrombocytopenia, muscle weakness, visual and cognitive disturbances, abdominal pain, renal failure, and disseminated intravascular coagulation. Although the presence of antiphospholipid antibodies in the blood is one of the diagnostic criteria, the level of these antibodies can fluctuate significantly, which complicates the diagnostic process and can lead to erroneous interpretation of rapidly developing symptoms. Triple therapy is often used to treat CAPS, which includes the use of anticoagulants, plasmapheresis, and high doses of glucocorticosteroids and, in some cases, additional intravenous immunoglobulins. The use of LMWH is recommended as the drug of choice due to its anti-inflammatory and anticoagulant properties. CAPS is a multifactorial disease that requires not only an interdisciplinary approach but also highly qualified medical care, adequate and timely diagnosis, and appropriate prevention in the context of relapse or occurrence of the disease. Improved new clinical protocols and education of medical personnel regarding CAPS can significantly improve the therapeutic approach and reduce mortality rates.
Topics: Humans; Antiphospholipid Syndrome; Heparin, Low-Molecular-Weight; Antibodies, Antiphospholipid; Anticoagulants; Cognitive Dysfunction
PubMed: 38203837
DOI: 10.3390/ijms25010668 -
Lupus Oct 2020Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent... (Review)
Review
Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Congresses as Topic; Factor Xa; Humans; Hydroxychloroquine; Thrombosis
PubMed: 33100166
DOI: 10.1177/0961203320950461 -
Journal of Thrombosis and Haemostasis :... Mar 2021Antiphospholipid syndrome (APS) is an acquired thromboinflammatory disorder characterized by the presence of antiphospholipid antibodies as well as an increased... (Review)
Review
Antiphospholipid syndrome (APS) is an acquired thromboinflammatory disorder characterized by the presence of antiphospholipid antibodies as well as an increased frequency of venous or arterial thrombosis and/or obstetrical morbidity. The spectrum of disease varies from asymptomatic to a severe form characterized by widespread thrombosis and multiorgan failure, termed catastrophic APS (CAPS). CAPS affects only about ∼1% of APS patients, often presents as a thrombotic microangiopathy and has a fulminant course with >40% mortality, despite the best available therapy. Animal models have implicated complement in the pathophysiology of thrombosis in APS, with more recent data from human studies confirming the interaction between the coagulation and complement pathways. Activation of the complement cascade via antiphospholipid antibodies can cause cellular injury and promote coagulation via multiple mechanisms. Finally, analogous to classic complement-mediated diseases such as atypical hemolytic uremic syndrome, a subset of patients with APS may be at increased risk for development of CAPS because of the presence of germline variants in genes crucial for complement regulation. Together, these data make complement inhibition an attractive and potentially lifesaving therapy to mitigate morbidity and mortality in severe thrombotic APS and CAPS.
Topics: Animals; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Complement Activation; Complement System Proteins; Humans; Mutation
PubMed: 32881236
DOI: 10.1111/jth.15082 -
Journal of Thrombosis and Haemostasis :... Apr 2023Antiphospholipid syndrome (APS) is a systemic autoimmune disease, where persistent presence of antiphospholipid antibodies (aPL) leads to thrombotic and obstetric... (Review)
Review
Antiphospholipid syndrome (APS) is a systemic autoimmune disease, where persistent presence of antiphospholipid antibodies (aPL) leads to thrombotic and obstetric complications. APS is a paradigmatic thromboinflammatory disease. Thromboinflammation is a pathophysiological mechanism coupling inflammation and thrombosis, which contributes to the pathophysiology of cardiovascular disease. APS can serve as a model to unravel mechanisms of thromboinflammation and the relationship between innate immune cells and thrombosis. Monocytes are activated by aPL into a proinflammatory and procoagulant phenotype, producing proinflammatory cytokines such as tumor necrosis factor α, interleukin 6, as well as tissue factor. Important cellular signaling pathways involved are the NF-κB-pathway, mammalian target of rapamycin (mTOR) signaling, and the NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome. All of these may serve as future therapeutic targets. Neutrophils produce neutrophil extracellular traps in response to aPL, and this leads to thrombosis. Thrombosis in APS also stems from increased interaction of neutrophils with endothelial cells through P-selectin glycoprotein ligand-1. NETosis can be targeted not only with several experimental therapeutics, such as DNase, but also through the redirection of current therapies such as defibrotide and the antiplatelet agent dipyridamole. Activation of platelets by aPL leads to a procoagulant phenotype. Platelet-leukocyte interactions are increased, possibly mediated by increased levels of soluble P-selectin and soluble CD40-ligand. Platelet-directed future treatment options involve the inhibition of several platelet receptors activated by aPL, as well as mTOR inhibition. This review discusses mechanisms underlying thromboinflammation in APS that present targetable therapeutic options, some of which may be generalizable to other thromboinflammatory diseases.
Topics: Female; Pregnancy; Humans; Antiphospholipid Syndrome; Thromboinflammation; Endothelial Cells; Inflammation; Thrombosis; TOR Serine-Threonine Kinases
PubMed: 36696191
DOI: 10.1016/j.jtha.2022.12.002