Platelets and neutrophils co-drive procoagulant potential in secondary antiphospholipid syndrome during pregnancy

Antiphospholipid syndrome (APS) is characterised by thrombosis and/or pregnancy morbidity with persistent antiphospholipid antibodies (aPL), and is commonly associated with systemic lupus erythematosus (SLE) [ [1] Schreiber K. Sciascia S. de Groot P.G. Devreese K. Jacobsen S. Ruiz-Irastorza G. Salmon J.E. Shoenfeld Y. Shovman O. Hunt B.J. Antiphospholipid syndrome. Nat. Rev. Dis. Primers. 2018; 4: 17103 Crossref PubMed Scopus (198) Google Scholar ]. APS is characterised by a prothrombotic and proinflammatory cytokine profile [ [1] Schreiber K. Sciascia S. de Groot P.G. Devreese K. Jacobsen S. Ruiz-Irastorza G. Salmon J.E. Shoenfeld Y. Shovman O. Hunt B.J. Antiphospholipid syndrome. Nat. Rev. Dis. Primers. 2018; 4: 17103 Crossref PubMed Scopus (198) Google Scholar ], and neutrophil activation and placental inflammation contributing to placental injury and fetal loss [ 1 Schreiber K. Sciascia S. de Groot P.G. Devreese K. Jacobsen S. Ruiz-Irastorza G. Salmon J.E. Shoenfeld Y. Shovman O. Hunt B.J. Antiphospholipid syndrome. Nat. Rev. Dis. Primers. 2018; 4: 17103 Crossref PubMed Scopus (198) Google Scholar , 2 Redecha P. Tilley R. Tencati M. Salmon J.E. Kirchhofer D. Mackman N. Girardi G. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood. 2007; 110: 2423-2431 Crossref PubMed Scopus (232) Google Scholar , 3 Redecha P. Franzke C.W. Ruf W. Mackman N. Girardi G. Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome. J. Clin. Invest. 2008; 118: 3453-3461 PubMed Google Scholar ]. Platelet activation and platelet-leucocyte aggregates (PLAs) are increased in APS [ [4] Joseph J.E. Harrison P. Mackie I.J. Isenberg D.A. Machin S.J. Increased circulating platelet-leucocyte complexes and platelet activation in patients with antiphospholipid syndrome, systemic lupus erythematosus and rheumatoid arthritis. Br. J. Haematol. 2001; 115: 451-459 Crossref PubMed Scopus (209) Google Scholar ], but their contribution to pregnancy complications is unclear. Platelets promote coagulation by providing a catalytic procoagulant surface and amplifying thrombin generation [ 5 Agbani E.O. Van den Bosch M.T.J. Brown E. Williams C.M. Mattheij N.J.A. Cosemans J.M.E.M. Collins P.W. Heemskerk J.W.M. Hers I. Poole A.W. Coordinated membrane ballooning and procoagulant spreading in human platelets. Circulation. 2015; 132: 1414-1424 Crossref PubMed Scopus (100) Google Scholar , 6 Agbani E.O. Poole A.W. Procoagulant platelets:-generation, function and therapeutic targeting in thrombosis. Blood. 2017; 130: 2171-2179 Crossref PubMed Scopus (84) Google Scholar ]. Despite therapy with low-molecular-weight heparin (LMWH) and aspirin, pregnancy in APS is associated with high rates of pregnancy loss, placenta-mediated complications and thromboembolism [ [7] Lo J.O. Mission J.F. Caughey A.B. Hypertensive disease of pregnancy and maternal mortality. Curr. Opin. Obstet. Gynecol. 2013; 25: 124-132 Crossref PubMed Scopus (241) Google Scholar ]. Understanding mechanisms underlying hypercoagulability and fetal loss is critical to improving pregnancy outcomes in APS.