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BMJ (Clinical Research Ed.) Feb 2023Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease propelled by circulating autoantibodies that recognize cell surface phospholipids and phospholipid... (Review)
Review
Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease propelled by circulating autoantibodies that recognize cell surface phospholipids and phospholipid binding proteins. The result is an increased risk of thrombotic events, pregnancy morbidity, and various other autoimmune and inflammatory complications. Although antiphospholipid syndrome was first recognized in patients with lupus, the stand alone presentation of antiphospholipid syndrome is at least equally common. Overall, the diagnosis appears to affect at least one in 2000 people. Studies of antiphospholipid syndrome pathogenesis have long focused on logical candidates such as coagulation factors, endothelial cells, and platelets. Recent work has shed light on additional potential therapeutic targets within the innate immune system, including the complement system and neutrophil extracellular traps. Vitamin K antagonists remain the mainstay of treatment for most patients with thrombotic antiphospholipid syndrome and, based on current data, appear superior to the more targeted direct oral anticoagulants. The potential role of immunomodulatory treatments in antiphospholipid syndrome management is receiving increased attention. As for many systemic autoimmune diseases, the most important future direction is to more precisely identify mechanistic drivers of disease heterogeneity in pursuit of unlocking personalized and proactive treatments for patients.
Topics: Female; Pregnancy; Humans; Antiphospholipid Syndrome; Endothelial Cells; Anticoagulants; Autoantibodies; Blood Platelets
PubMed: 36849186
DOI: 10.1136/bmj-2021-069717 -
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 -
Best Practice & Research. Clinical... Feb 2020Antiphospholipid syndrome is an autoimmune systemic disorder characterized by arterial, venous, or small vessel thrombosis and/or recurrent early pregnancy loss, fetal... (Review)
Review
Antiphospholipid syndrome is an autoimmune systemic disorder characterized by arterial, venous, or small vessel thrombosis and/or recurrent early pregnancy loss, fetal loss, or pregnancy morbidity in the setting of documented persistent antiphospholipid antibodies that include the lupus anticoagulant, or moderate-high titer anticardiolipin, or anti-β2Glycoprotein I antibodies. Associated clinical manifestations include livedo reticularis, cutaneous ulcerations, thrombocytopenia, hemolytic anemia, valvular heart disease, and nephropathy. The degree of risk associated with antiphospholipid antibody depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors. Current standard treatment for unprovoked thrombosis is long-term warfarin or other vitamin K antagonist therapy. Treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin, usually low-molecular-weight heparin. Optimal treatment for standard therapy failures or for certain nonthrombotic manifestations is uncertain, although nonanticoagulation therapies that address multiple demonstrated mechanisms of disease are being explored.
Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Embryo Loss; Female; Humans; Lupus Coagulation Inhibitor; Pregnancy
PubMed: 31866276
DOI: 10.1016/j.berh.2019.101463 -
The New England Journal of Medicine May 2018
Review
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Humans; Thrombosis; Warfarin
PubMed: 29791828
DOI: 10.1056/NEJMra1705454 -
Frontiers in Immunology 2019
Topics: Antiphospholipid Syndrome; Diagnosis, Differential; Disease Susceptibility; Humans; Lupus Erythematosus, Systemic
PubMed: 30858846
DOI: 10.3389/fimmu.2019.00199 -
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 -
Hematology. American Society of... Dec 2023Antiphospholipid antibodies (aPL) are autoimmune antibodies directed toward phospholipids or phospholipid-protein complexes, particularly those containing... (Review)
Review
Antiphospholipid antibodies (aPL) are autoimmune antibodies directed toward phospholipids or phospholipid-protein complexes, particularly those containing β2-glycoprotein I (β2GPI). Persistently positive aPL accompanied by arterial or venous thrombosis, or recurrent pregnancy loss, constitutes the antiphospholipid syndrome (APS). Several types of aPL with different specificities have been defined and may be detected in the clinical lab, including lupus anticoagulants (detected using clotting assays) and anticardiolipin, anti-β2GPI and anti-prothrombin/phosphatidylserine antibodies (detected by ELISA); each of the last 3 aPL may be either IgG, IgM, or IgA, though IgA antibodies are not included in criteria for APS. Due to the relative rarity of APS and the heterogeneity of aPL, thrombosis risk stratification is challenging, and randomized clinical trials for thrombosis treatment and prevention have been limited. This lack of high-quality data has made the clinical management of APS difficult, and existing guidelines are few and could not possibly cover many of the scenarios encountered in managing patients with APS. In this review, we present 3 patients with aPL and/or APS who highlight treatment dilemmas, and we discuss background information that may help guide clinical judgment in developing individualized treatment plans for patients with these enigmatic antibodies.
Topics: Female; Pregnancy; Humans; Antiphospholipid Syndrome; Antibodies, Antiphospholipid; Lupus Coagulation Inhibitor; beta 2-Glycoprotein I; Thrombosis; Immunoglobulin A
PubMed: 38066904
DOI: 10.1182/hematology.2023000493 -
International Journal of Stroke :... Apr 2023Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disease with heterogeneous clinicopathological manifestations and is a well-established cause of acute... (Review)
Review
Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disease with heterogeneous clinicopathological manifestations and is a well-established cause of acute ischemic stroke (AIS) and transient ischemic attack (TIA), particularly in younger patients. There is growing recognition of a wider spectrum of APS-associated cerebrovascular lesions, including white matter hyperintensities, cortical atrophy, and infarcts, which may have clinically important neurocognitive sequalae. Diagnosis of APS-associated AIS/TIA requires expert review of clinical and laboratory information. Management poses challenges, given the potential for substantial morbidity and recurrent thrombosis, additional risk conferred by conventional cardiovascular risk factors, and limited evidence base regarding optimal antithrombotic therapy for secondary prevention. In this review, we summarize key features of APS-associated cerebrovascular disorders, with focus on clinical and laboratory aspects of diagnostic evaluation. The current status of prognostic markers is considered. We review the evidence base for antithrombotic treatment in APS-associated stroke and discuss uncertainties, including the optimal intensity of anticoagulation and efficacy of direct oral anticoagulants. Clinical practice recommendations are provided, covering antithrombotic treatment, supportive management, and options for anticoagulant-refractory cases, and we highlight the benefits of adopting a considered, multidisciplinary team approach.
Topics: Humans; Antiphospholipid Syndrome; Stroke; Ischemic Stroke; Fibrinolytic Agents; Ischemic Attack, Transient; Antibodies, Antiphospholipid; Anticoagulants
PubMed: 36571450
DOI: 10.1177/17474930221150349 -
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