Circulating microparticles, lupus anticoagulant and recurrent miscarriages

Abstract 

Pregnancy is a pro-inflammatory/hypercoagulable state. Impairment of trophoblastic invasion and placental microthrombi are involved mechanisms in the pathogenesis of recurrent miscarriages (RM). Although in RM related to antiphospholipid antibodies (aPL) non-thrombotic mechanism seems to play an important role as well, we focused this review on the thrombotic mechanisms of RM related to aPL. Thus, in cases of RM related to aPL, placental injury produces inflammatory changes in endothelial cells. Endothelial dysfunction has been shown by increased plasma levels of ICAM-1/VCAM-1 and E-selectin. In RM associated with aPL, the thrombogenic mechanisms included different pathways: protein C inhibition, annexin-5 displacement, blocking of β₂GP1 anticoagulant activity and tissue factor upregulation. A new marker/causative agent of RM by itself or in relation to lupus anticoagulant (LA) has risen: circulating microparticles. Microparticles are a heterogeneous group of small, membrane-coated vesicles with a diameter of 0.1–1μm. Microparticles are released from the cellular membrane during cell activation/apoptosis. Exposition of phospholipids in the outer membrane leaflet could explain the role of microparticles in the thrombotic events. Microparticles have been associated with RM. Microparticles are increased in women with RM when compared with healthy pregnant women. A relationship between aPL and activated endothelial cells (EC) occurs, as well as between EC and circulating microparticles. Interestingly, microparticles induced coagulation in vitro via tissue factor, especially in plasmas with LA. Finally, the relationship between EC, microparticles, LA and RM is revised.

Keywords: Annexin-A5, Antiphospholipid antibodies, Cellular microparticles, Endothelial activation, Lupus anticoagulant, Recurrent miscarriages