Journal Article•
Primary antiphospholipid syndrome
TL;DR: Primary APS occurs when there is no evidence of associated diseases, and APS in the presence of an underlying disease, usually systemic lupus erythematosus, is called secondary APS.
Abstract: Antiphospholipid syndrome (APS) is a disorder characterised by recurrent arterial or venous thrombosis and/or pregnancy losses, in the presence of persistently elevated levels of anticardiolipin antibodies and/or evidence of circulating lupus anticoagulant (these abnormalities are detected by blood tests). Primary APS occurs when there is no evidence of associated diseases. APS in the presence of an underlying disease, usually systemic lupus erythematosus, is called secondary APS.
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TL;DR: The objective of this review paper is to summarize the recent literature on APS from pathogenesis to current therapeutic options.
Abstract: Antiphospholipid antibody syndrome (APS) is an autoimmune acquired thrombophilia characterized by recurrent thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). APS can be primary, if it occurs in the absence of any underlying disease, or secondary, if it is associated with another autoimmune disorder, most commonly systemic lupus erythematosus. The exact pathogenetic mechanism of APS is unknown, but different, not mutually exclusive, models have been proposed to explain how anti-PL autoantibodies might lead to thrombosis and pregnancy morbidity. Diagnosis of APS requires that a patient has both a clinical manifestation (arterial or venous thrombosis and/or pregnancy morbidity) and persistently positive aPL, but the clinical spectrum of the disease encompasses additional manifestations which may affect every organ and cannot be explained exclusively by a prothrombotic state. Treatment for aPL-positive patients is based on the patient's clinical status, presence of an underlying autoimmune disease, and history of thrombotic events. In case of aPL positivity without previous thrombotic events, the treatment is mainly focused on reduction of additional vascular risk factors, while treatment of patients with definite APS is based on long-term anticoagulation. Pregnancy complications are usually managed with low-dose aspirin in association with low molecular weight heparin. Refractory forms of APS could benefit from adding hydroxychloroquine and/or intravenous immunoglobulin to anticoagulation therapy. Promising novel treatments include anti-B cell monoclonal antibodies, new-generation anticoagulants, and complement cascade inhibitors. The objective of this review paper is to summarize the recent literature on APS from pathogenesis to current therapeutic options.
85 citations
Cites background from "Primary antiphospholipid syndrome"
...APS is defined ‘‘primary’’ if it is not associated with other underlying diseases or ‘‘secondary’’ if it occurs in association with other conditions, such as autoimmune disorders, particularly systemic lupus erythematosus (SLE) [8, 9]. aPL positivity has been also described in concomitance with infections, drugs, and malignancies; however, in these cases, aPL titers are usually transient and low, therefore not increasing the risk of thrombosis or of an adverse pregnancy outcome [10–12]....
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...In patients with aPL associated with SLE, LDA and hydroxychloroquine (HCQ) are commonly prescribed as primary thromboprophylaxis....
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...In addition, 11–29 % of women with preeclampsia and 25 % of women with growth-restricted fetuses have a positive aPL test [18]. aPL can be detected in up to 50 % of SLE patients, while aPL prevalence in other connective tissue diseases such as rheumatoid arthritis, dermatomyositis, Sjögren’s syndrome, and systemic sclerosis, is lower and ranges from 5 to 20 % [10, 19–22]....
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...Furthermore, in patients with APS and SLE, APS renal disease may coexist with immune complex-mediated lupus nephritis....
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...Preconception counseling and strict maternal and fetal surveillance during the whole length of the pregnancy are advised, particularly in women with SLE....
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TL;DR: Small vessel occlusions may occur as part of the vascular manifestations of the Antiphospholipid Syndrome and may affect glomerular, skin, retinal, bowel, hepatic or pulmonary vessels, and the term "MAPS" is suggested for these two groups of conditions.
63 citations
Cites background from "Primary antiphospholipid syndrome"
...Most patients with aPL-related thromboses appear to suffer from the “Primary” APS [7] (PAPS) or systemic lupus erythematosus (SLE)....
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TL;DR: Assessment of 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 a-PL antibodies.
Abstract: 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.
57 citations
Cites background from "Primary antiphospholipid syndrome"
...However, shortly after, several authors suggested a separate category to group patients with APS clinical criteria and without systemic autoimmune disorders: the primary antiphospholipid syndrome (PAPS) [4, 5], currently the most common form of disease [6]....
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TL;DR: A multiorgan involvement that cannot be explained by the thrombophilic state per se and similar to the well known clinical manifestations in lupus is reported in patients with primary antiphospholipid syndrome.
Abstract: Purpose of review Although originally described in the context of systemic lupus erythematosus, antiphospholipid syndrome was then recognized as a primary antiphospholipid syndrome without any underlying autoimmune disease in almost half of the cases. However, cases of primary antiphospholipid syndrome were reported to evolve into systemic lupus erythematosus over time suggesting that these apparently different diseases are somehow related. Recent findings Peculiar biological systemic lupus erythematosus markers such as an autoantibody response against chromatin antigens and complement activation have been also described in patients with primary antiphospholipid syndrome. Distinct polymorphisms of common genetic factors have been associated with systemic lupus erythematosus and primary antiphospholipid syndrome supporting the notion that these entities are indeed variants within a continuum of the same disease. Summary A multiorgan involvement that cannot be explained by the thrombophilic state per se and similar to the well known clinical manifestations in lupus is reported in patients with primary antiphospholipid syndrome. Further studies, mainly genetic, will better underline the proximity between primary antiphospholipid syndrome and systemic lupus erythematosus.
57 citations
TL;DR: Although large-vessel occlusions do occur in catastrophic APS, they do not dominate the clinical picture, and their frequency is completely different from that encountered in the classic APS itself.
Abstract: Revealing the evolution of the term APS and its commonalities with other microangiopathic disorders
The occurrence of small-vessel occlusions (thrombotic microangiopathy) in association with anti-phospholipid antibodies (aPL) affecting, for example, the retinal vessels,1 the nail fold,2,3 the skin,4 or major intrabdominal organs such as the kidney, the liver or the bowel,5 although uncommon, is well documented. These occlusions have been described in the simple or classic antiphospholipid syndrome (APS), whether or not associated with systemic lupus erythematosus (SLE), or in the primary APS,6 but they do not in any way dominate the clinical picture in these conditions. However, with the description and definition of the catastrophic APS (also known as Asherson’s syndrome) in 19927,8 (a new subset of the APS, often fatal, with many distinguishing characteristics separating it from the simple APS),9–11 there has been renewed interest in the thrombotic microangiopathies and their association with aPL. Although large-vessel occlusions do occur in catastrophic APS, they do not dominate the clinical picture, and their frequency is completely different from that encountered in the classic APS itself. Additionally, the catastrophic APS is frequently accompanied by a systemic inflammatory response syndrome (SIRS).
The term thrombotic microangiopathic haemolytic anaemia (TMHA) was originally introduced by Symmers12 in 1952 to describe a clinical state with localised or diffuse microvascular thrombosis in association with haemolytic anaemia and fragmented red cells referred to as schistocytes. Indeed, the great haematologist John Dacie and his colleagues13 published a seminal paper on TMHA and related the condition to vascular damage some 10 years later. TMHA encompasses a spectrum of disorders including thrombotic thrombocytopenic purpura (TTP), haemolytic–uraemic syndrome (HUS), malignant hypertension, postpartum renal failure, pre-eclampsia and catastrophic APS. Recent articles still refer to the difficulty in distinguishing among these conditions …
39 citations
References
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TL;DR: The objective of this review paper is to summarize the recent literature on APS from pathogenesis to current therapeutic options.
Abstract: Antiphospholipid antibody syndrome (APS) is an autoimmune acquired thrombophilia characterized by recurrent thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). APS can be primary, if it occurs in the absence of any underlying disease, or secondary, if it is associated with another autoimmune disorder, most commonly systemic lupus erythematosus. The exact pathogenetic mechanism of APS is unknown, but different, not mutually exclusive, models have been proposed to explain how anti-PL autoantibodies might lead to thrombosis and pregnancy morbidity. Diagnosis of APS requires that a patient has both a clinical manifestation (arterial or venous thrombosis and/or pregnancy morbidity) and persistently positive aPL, but the clinical spectrum of the disease encompasses additional manifestations which may affect every organ and cannot be explained exclusively by a prothrombotic state. Treatment for aPL-positive patients is based on the patient's clinical status, presence of an underlying autoimmune disease, and history of thrombotic events. In case of aPL positivity without previous thrombotic events, the treatment is mainly focused on reduction of additional vascular risk factors, while treatment of patients with definite APS is based on long-term anticoagulation. Pregnancy complications are usually managed with low-dose aspirin in association with low molecular weight heparin. Refractory forms of APS could benefit from adding hydroxychloroquine and/or intravenous immunoglobulin to anticoagulation therapy. Promising novel treatments include anti-B cell monoclonal antibodies, new-generation anticoagulants, and complement cascade inhibitors. The objective of this review paper is to summarize the recent literature on APS from pathogenesis to current therapeutic options.
85 citations
TL;DR: Small vessel occlusions may occur as part of the vascular manifestations of the Antiphospholipid Syndrome and may affect glomerular, skin, retinal, bowel, hepatic or pulmonary vessels, and the term "MAPS" is suggested for these two groups of conditions.
63 citations
TL;DR: Assessment of 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 a-PL antibodies.
Abstract: 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.
57 citations
TL;DR: A multiorgan involvement that cannot be explained by the thrombophilic state per se and similar to the well known clinical manifestations in lupus is reported in patients with primary antiphospholipid syndrome.
Abstract: Purpose of review Although originally described in the context of systemic lupus erythematosus, antiphospholipid syndrome was then recognized as a primary antiphospholipid syndrome without any underlying autoimmune disease in almost half of the cases. However, cases of primary antiphospholipid syndrome were reported to evolve into systemic lupus erythematosus over time suggesting that these apparently different diseases are somehow related. Recent findings Peculiar biological systemic lupus erythematosus markers such as an autoantibody response against chromatin antigens and complement activation have been also described in patients with primary antiphospholipid syndrome. Distinct polymorphisms of common genetic factors have been associated with systemic lupus erythematosus and primary antiphospholipid syndrome supporting the notion that these entities are indeed variants within a continuum of the same disease. Summary A multiorgan involvement that cannot be explained by the thrombophilic state per se and similar to the well known clinical manifestations in lupus is reported in patients with primary antiphospholipid syndrome. Further studies, mainly genetic, will better underline the proximity between primary antiphospholipid syndrome and systemic lupus erythematosus.
57 citations
TL;DR: Although large-vessel occlusions do occur in catastrophic APS, they do not dominate the clinical picture, and their frequency is completely different from that encountered in the classic APS itself.
Abstract: Revealing the evolution of the term APS and its commonalities with other microangiopathic disorders
The occurrence of small-vessel occlusions (thrombotic microangiopathy) in association with anti-phospholipid antibodies (aPL) affecting, for example, the retinal vessels,1 the nail fold,2,3 the skin,4 or major intrabdominal organs such as the kidney, the liver or the bowel,5 although uncommon, is well documented. These occlusions have been described in the simple or classic antiphospholipid syndrome (APS), whether or not associated with systemic lupus erythematosus (SLE), or in the primary APS,6 but they do not in any way dominate the clinical picture in these conditions. However, with the description and definition of the catastrophic APS (also known as Asherson’s syndrome) in 19927,8 (a new subset of the APS, often fatal, with many distinguishing characteristics separating it from the simple APS),9–11 there has been renewed interest in the thrombotic microangiopathies and their association with aPL. Although large-vessel occlusions do occur in catastrophic APS, they do not dominate the clinical picture, and their frequency is completely different from that encountered in the classic APS itself. Additionally, the catastrophic APS is frequently accompanied by a systemic inflammatory response syndrome (SIRS).
The term thrombotic microangiopathic haemolytic anaemia (TMHA) was originally introduced by Symmers12 in 1952 to describe a clinical state with localised or diffuse microvascular thrombosis in association with haemolytic anaemia and fragmented red cells referred to as schistocytes. Indeed, the great haematologist John Dacie and his colleagues13 published a seminal paper on TMHA and related the condition to vascular damage some 10 years later. TMHA encompasses a spectrum of disorders including thrombotic thrombocytopenic purpura (TTP), haemolytic–uraemic syndrome (HUS), malignant hypertension, postpartum renal failure, pre-eclampsia and catastrophic APS. Recent articles still refer to the difficulty in distinguishing among these conditions …
39 citations