Antiphospholipid syndrome: an update

Merashli, Mira; Noureldine, Mohammad Hassan A.; Uthman, Imad; Khamashta, Munther A.

doi:10.1111/eci.12449

Cited by 40 publications

(24 citation statements)

References 112 publications

(112 reference statements)

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“…Nevertheless, it was recently demonstrated that APS patients may have antibodies that bind cardiolipin without serum protein cofactor, and these antibodies are prothrombotic in mice [8]. The heterogeneity of antiphospholipid antibodies and the wide range of clinical features in APS patients suggest that there are multiple pathways leading to the disease [9–11]. …”

Section: Introductionmentioning

confidence: 99%

Dimerized Domain V of Beta2-Glycoprotein I Is Sufficient to Upregulate Procoagulant Activity in PMA-Treated U937 Monocytes and Require Intact Residues in Two Phospholipid-Binding Loops

2017

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Upregulation of the procoagulant activity of monocytes by antibodies to beta2- glycoprotein I (β2GPI) is one of the mechanisms contributing to thrombosis in antiphospholipid syndrome. Current knowledge about receptors responsible for the upregulation of procoagulant activity by β2GPI/anti-β2GPI complexes and their binding sites on β2GPI is far from complete. We quantified the procoagulant activity expressed by phorbol 12-myristate 13-acetate (PMA)- differentiated U937 cells by measuring clotting kinetics in human plasma exposed to stimulated cells. Cells stimulated with anti-β2GPI were compared to cells treated with dimerized domain V of β2GPI (β2GPI-DV) or point mutants of β2GPI-DV. We demonstrated that dimerized β2GPI-DV is sufficient to induce procoagulant activity in monocytes. Using site-directed mutagenesis, we determined that the phospholipid-binding interface on β2GPI is larger than previously thought and includes Lys308 in β2GPI-DV. Intact residues in two phospholipid-binding loops of β2GPI-DV were important for the potentiation of procoagulant activity. We did not detect a correlation between the ability of β2GPI-DV variants to bind ApoER2 and potentiation of the procoagulant activity of cells. The region on β2GPI inducing procoagulant activity in monocytes can now be narrowed down to β2GPI-DV. The ability of β2GPI-DV dimers to come close to cell membrane and attach to it is important for the stimulation of procoagulant activity.

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Section: Introductionmentioning

confidence: 99%

Dimerized Domain V of Beta2-Glycoprotein I Is Sufficient to Upregulate Procoagulant Activity in PMA-Treated U937 Monocytes and Require Intact Residues in Two Phospholipid-Binding Loops

2017

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“…The aPLs are positive in approximately 13% of patients with stroke, 11% with myocardial infarction, 9.5% of patients with deep vein thrombosis and 6% of patients with pregnancy morbidity [16]. These data can underline the significance of APS.…”

Section: Epidemiology Of Apsmentioning

confidence: 77%

“…Cyclophosphamide can also be used in CAPS in the presence of secondary autoimmune disease such as SLE [15]. Rituximab can also be used in refractory cases after failure or inability to take the above-mentioned combined therapies or in the presence of micro-angiopathic haemolytic anaemia [16].…”

Section: About Antiphospholipid Syndromementioning

confidence: 99%

Antiphospholipid Syndrome and Thrombocytopenia

Gadó¹,

Domján²

2018

Thrombocytopenia

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Antiphospholipid syndrome is characterised by arterial and venous thromboembolic events and pregnancy morbidity (mainly, recurrent foetal losses), in the presence of antiphospholipid antibodies. Diagnosis is based on the presence of at least one laboratory and at least one clinical manifestation of antiphospholipid syndrome. There are also socalled "non-criteria" clinical features, and thrombocytopenia is one of the most important among them. Thrombocytopenia has been reported with a prevalence between 30 and 46% among patients with antiphospholipid syndrome. The pathogenesis of thrombocytopenia related to antiphospholipid antibodies is not absolutely clear. Binding of antiphospholipid antibodies to platelets and the promotion of platelet activation and aggregation thus thrombus formation must be an important mechanism as well as the immune-mediated clearance of platelets. Thrombocytopenia in antiphospholipid syndrome is usually mild and does not require clinical intervention. The presence of thrombocytopenia in patients with antiphospholipid syndrome is typically associated not with haemorrhagic complications, rather it can trigger thrombotic events. Other causes of thrombocytopenia, such as TTP, SLE, MDS, and ITP should be excluded. As thrombocytopenia is usually mild and it predicts later thrombosis, patients may be given platelet aggregation inhibitors and/ or anticoagulant therapy. Anti-thrombotic treatment should be stopped only in case of severe thrombocytopenia.

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“…A prospective study did not detect any benefit from using LDA, 28 but a meta-analysis of 11 studies did detect a protective action from this intervention against thrombotic events (arterial, but not venous), and although this protection was eliminated when the analysis was restricted to prospective and higher-quality studies, 1,29 another meta-analysis that used individual patient data from five cohorts also found evidence of protection.…”

Section: Primary Thromboprophylaxismentioning

confidence: 99%

A importância de reconhecer a síndrome antifosfolípide na medicina vascular

et al. 2017

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Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent arterial or venous thrombosis and/or gestational morbidity and by the presence of antiphospholipid antibodies. It can also cause other vascular manifestations such as microangiopathy, chronic arteriopathy and catastrophic APS (CAPS). Certain laboratory tests for the syndrome (for example, the lupus anticoagulant test) can be affected by the use of anticoagulant agents, making diagnosis more difficult. The pathophysiology of APS is complex, and several mechanisms of pathogenesis related to coagulation, endothelium, and platelets are discussed in this article. We conclude by discussing treatment of APS according to the presence and type of clinical manifestations, use of direct oral anticoagulants (DOAs), and perioperative management of patients with APS.Keywords: antiphospholipid syndrome; lupus anticoagulant; anticardiolipin antibodies; thrombosis; autoimmunity. ResumoA síndrome antifosfolipíde (SAF) é uma doença autoimune sistêmica caracterizada por trombose arterial ou venosa recorrente e/ou morbidade gestacional e pela presença dos anticorpos antifosfolipídeos, podendo apresentar outras manifestações vasculares, como microangiopatia, arteriopatia crônica e SAF catastrófica. Determinados testes laboratoriais para a síndrome (por exemplo, o anticoagulante lúpico) podem sofrer interferência do uso de medicações anticoagulantes, dificultando o diagnóstico. A fisiopatologia da SAF é complexa, sendo enumerados no texto diversos mecanismos patogênicos relacionados à coagulação, ao endotélio e às plaquetas. Por fim, discutimos o tratamento da SAF de acordo com a presença e o tipo de manifestações clínicas, o uso dos anticoagulantes orais diretos e o manejo perioperatório de pacientes com SAF.Palavras-chave: síndrome antifosfolípide; anticoagulante do lúpus; anticorpos anticardiolipina; trombose; autoimunidade.

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Antiphospholipid syndrome: an update

Cited by 40 publications

References 112 publications

Dimerized Domain V of Beta2-Glycoprotein I Is Sufficient to Upregulate Procoagulant Activity in PMA-Treated U937 Monocytes and Require Intact Residues in Two Phospholipid-Binding Loops

Dimerized Domain V of Beta2-Glycoprotein I Is Sufficient to Upregulate Procoagulant Activity in PMA-Treated U937 Monocytes and Require Intact Residues in Two Phospholipid-Binding Loops

Antiphospholipid Syndrome and Thrombocytopenia

A importância de reconhecer a síndrome antifosfolípide na medicina vascular

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