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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 -
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 -
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 -
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 -
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 -
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 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 -
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 -
Thrombosis Research Sep 2019Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL). The antibodies currently included in the... (Review)
Review
Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies (aPL). The antibodies currently included in the classification criteria include lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-^2-glycoprotein 1 antibodies (^2GPI). APS can present with a variety of clinical phenotypes, including thrombosis in the veins, arteries and microvasculature and obstetrical complications. Pregnancy complications in obstetric APS (OAPS) include unexplained recurrent early pregnancy loss, fetal death, or premature birth due to severe preeclampsia, eclampsia, intrauterine growth restriction or other consequences of placental insufficiency. Careful, well monitored obstetric care with the use of aspirin and heparin has likely improved the pregnancy outcome in obstetric APS and currently approximately 70-80% of pregnant women with APS have a successful pregnancy outcome. However, the current standard of care does not prevent all pregnancy complications as the current treatment fails in 20-30% of APS pregnancies. Other treatments options are currently being explored and retrospective studies suggest that trials with hydroxychloroquine and possibly pravastatin are warranted in pregnant women with aPL. In this review will focus on the current treatment of OAPS.
Topics: Antiphospholipid Syndrome; Female; Humans; Pregnancy; Pregnancy Outcome
PubMed: 31477227
DOI: 10.1016/S0049-3848(19)30366-4