Targeting thromboinflammation in antiphospholipid syndrome

Salet, Dorien M.; Bekkering, Siroon; Hoogen, Lucas L van den

doi:10.1016/j.jtha.2022.12.002

Cited by 16 publications

(10 citation statements)

References 116 publications

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“…TAPS patients had higher rates of cardiovascular morbidity compared with OAPS. Previous research emphasizes that cardiovascular morbidity is involved in the thrombotic phenotype mechanism [ 42 , 43 ], and recent research [ 43 ] focuses on simvastatin and fluvastatin in the treatment of APS. Simvastatin and fluvastatin hinder endothelial activation linked to anti-β2GPI.…”

Section: Discussionmentioning

confidence: 99%

“…These results further support the need for specific treatment in different APS phenotypes. Recently, a notable emphasis on neutrophil extracellular trap [ 45 , 46 ] formation has been observed in TAPS, particularly in individuals with triple antiphospholipid positivity and recurrent thrombosis [ 43 ]. Potential therapeutic strategies include DNase-mediated digestion of neutrophil extracellular traps and anti-β2GPI-induced tumor necrosis factor-α effects through adalimumab and certolizumab [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Obstetric antiphospholipid syndrome carries an increased lifetime risk for obstetric and thrombotic complications—a population-based study

Rhein,

Rabinovich,

Abuhasira

et al. 2024

Research and Practice in Thrombosis and Haemostasis

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Obstetric antiphospholipid syndrome carries an increased lifetime risk for obstetric and thrombotic complications—a population-based study

Rhein,

Rabinovich,

Abuhasira

et al. 2024

Research and Practice in Thrombosis and Haemostasis

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“…A recent review described the induction of TF expression in monocytes by antiphospholipid antibodies. 149 …”

Section: Discussionmentioning

confidence: 99%

Monocyte Tissue Factor Expression: Lipopolysaccharide Induction and Roles in Pathological Activation of Coagulation

Sachetto

Mackman

2023

Thromb Haemost

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The coagulation system is a part of the mammalian host defense system. Pathogens and pathogen components, such as bacterial lipopolysaccharide (LPS), induce tissue factor (TF) expression in circulating monocytes that then activates the coagulation protease cascade. Formation of a clot limits dissemination of pathogens, enhances the recruitment of immune cells and facilitates killing of pathogens. However, excessive activation of coagulation can lead to thrombosis. Here, we review studies on the mechanism of LPS induction of TF expression in monocytes and its contribution to thrombosis and disseminated intravascular coagulation. Binding of LPS to Toll-like receptor 4 on monocytes induces a transient TF expression that involves activation of intracellular signaling pathways and binding of various transcription factors, such as c-rel/p65 and c-Fos/c-Jun, to the TF promoter. Inhibition of TF in endotoxemia and sepsis models reduces activation of coagulation and improves survival. Studies with endotoxemic mice showed that hematopoietic cells and myeloid cells play major roles in the activation of coagulation. Monocyte TF expression is also increased after surgery. Activated monocytes release TF-positive extracellular vesicles (EVs) and levels of circulating TF-positive EVs are increased in endotoxemic mice and in patients with sepsis. More recently, it was shown that inflammasomes contribute to the induction of TF expression and activation of coagulation in endotoxemic mice. Taken together, these studies indicate that monocyte TF plays a major role in the LPS-induced activation of coagulation. Selective inhibition of monocyte TF expression may reduce pathologic activation of coagulation in sepsis and other diseases.

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“…Severe thrombocytopenia is correlated with disease activity and a worse prognosis of SLE-associated thrombocytopenia (SLE-TP) [ 2 , 3 ]. Antiphospholipid antibodies (aPLs) have been proven to cause thrombocytopenia through various mechanisms [ 4 ]. However, the mechanisms of thrombocytopenia in SLE patients are not fully known and may involve the production, destruction, and distribution of platelets.…”

Section: Introductionmentioning

confidence: 99%

Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study

Li,

Peng,

et al. 2024

Arthritis Res Ther

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Background To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP). Methods This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 109/L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected. Results A total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 109/L vs. 76.5 × 109/L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 109/L vs. 51.0 × 109/L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories. Conclusion SLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate.

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Targeting thromboinflammation in antiphospholipid syndrome

Cited by 16 publications

References 116 publications

Obstetric antiphospholipid syndrome carries an increased lifetime risk for obstetric and thrombotic complications—a population-based study

Obstetric antiphospholipid syndrome carries an increased lifetime risk for obstetric and thrombotic complications—a population-based study

Monocyte Tissue Factor Expression: Lipopolysaccharide Induction and Roles in Pathological Activation of Coagulation

Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study

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