{"id":65793,"date":"2026-05-30T07:14:16","date_gmt":"2026-05-30T05:14:16","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/05\/30\/novel-mechanisms-linking-platelet-activation-to-antiphospholipid-syndrome\/"},"modified":"2026-05-30T07:14:16","modified_gmt":"2026-05-30T05:14:16","slug":"novel-mechanisms-linking-platelet-activation-to-antiphospholipid-syndrome","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/05\/30\/novel-mechanisms-linking-platelet-activation-to-antiphospholipid-syndrome\/","title":{"rendered":"Novel mechanisms linking platelet activation to antiphospholipid syndrome"},"content":{"rendered":"<div>\n<p><b>Curr Opin Immunol<\/b>. 2026 May 29;101:102791. doi: 10.1016\/j.coi.2026.102791. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Antiphospholipid syndrome (APS) is a thromboinflammatory disorder in which antiphospholipid antibodies (aPL), particularly anti-\u03b22GPI, initiate a complex, graded platelet activation that integrates immune signaling with coagulation. Clinical and multiparametric flow-cytometric evidence demonstrates a sustained prothrombotic platelet endotype characterized by enrichment of tissue factor-positive (TF<sup>pos<\/sup>)-platelets, an increase in the number of TF<sup>pos<\/sup>-platelet-leukocyte heteroaggregates, and in the expression of classical adhesion markers (P selectin, activated \u03b1IIb\u03b23) despite anticoagulation. These abnormalities correlate with high-risk aPL profiles and likely contribute to residual thrombotic risk not captured by conventional coagulation biomarkers. Pathogenic anti-\u03b22GPI &#8211; especially Domain 1 specific-IgG &#8211; induce a selective, early procoagulant TF<sup>pos<\/sup>-phenotype in the absence of full adhesive activation. This phenotype reflects peripheral ApoER2-dependent signaling rather than bone marrow-driven megakaryocyte programming. Inflammatory mediators, notably IL6, act as indispensable amplifiers, converting the TF-only phenotype into a broader thromboinflammatory program involving P-selectin expression, integrin activation, phosphatidylserine exposure, and formation of multicellular immunothrombotic units. Omics-based profiling corroborates a chronically primed platelet state with dysregulated inhibitory checkpoints (CD73-adenosine-cAMP axis), enhanced ADP\/P2Y<sub>12<\/sub> signaling, and membrane remodeling conducive to procoagulant differentiation. TF<sup>pos<\/sup>-platelets emerge as a mechanistically grounded biomarker candidate of thrombotic propensity and a potential therapeutic target. Ex vivo data show distinct pharmacological sensitivity since aspirin and P2Y<sub>12<\/sub> inhibition attenuate both adhesive and TF-dependent procoagulant programs, whereas hydroxychloroquine selectively modulates classical activation markers but not platelet-associated TF. These observations delineate separable adhesive vs. procoagulant platelet modules and support a precision medicine framework in which quantification and targeted suppression of TF<sup>pos<\/sup>-platelets may attenuate the basal prothrombotic milieu and mitigate APS-related thrombotic risk.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42214306\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=8900118&amp;ff=20260530011415&amp;v=2.20.0\">42214306<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.coi.2026.102791\">10.1016\/j.coi.2026.102791<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Curr Opin Immunol. 2026 May 29;101:102791. doi: 10.1016\/j.coi.2026.102791. Online ahead of print. ABSTRACT Antiphospholipid syndrome (APS) is a thromboinflammatory disorder in which antiphospholipid antibodies (aPL), particularly anti-\u03b22GPI, initiate a complex, graded platelet activation that integrates immune signaling with coagulation. Clinical and multiparametric flow-cytometric evidence demonstrates a sustained prothrombotic platelet endotype characterized by enrichment of tissue &#8230; <a title=\"Novel mechanisms linking platelet activation to antiphospholipid syndrome\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/05\/30\/novel-mechanisms-linking-platelet-activation-to-antiphospholipid-syndrome\/\" aria-label=\"Read more about Novel mechanisms linking platelet activation to antiphospholipid syndrome\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[59,42],"tags":[],"class_list":["post-65793","post","type-post","status-publish","format-standard","hentry","category-current-opinion-in-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/65793","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=65793"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/65793\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=65793"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=65793"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=65793"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}