**3. Pathogenesis of obstetric antiphospholipid syndrome**

The exact etiopathogenetic mechanism liable for obstetric morbidity in APS is not yet known. The aPLs are not only a diagnostic marker but have a key role in determining thrombosis and obstetric complications [42]. In the early stages, during pregnancy, the cytotrophoblastic cells differentiates into two cell types. The villous trophoblast will fuse to form the syncytiotrophoblast, a barrier of protection between the mother and the fetus. While, the extravillous trophoblast will progressively invade and colonize the maternal endometrium [43]. aPLs target the placenta, especially the cytotrophoblastic cells. Trophoblast, synthetize β2GPI, a 70 kDa cationic protein that is normally in a "closed conformation", when free in the plasma of patients. It is composed of five homologous domains of approximately 60 amino acids each. Domains I and V are the two domains positively charged [44]. During normal pregnancy and syncytiotrophoblast formation, anionic phospholipids are externalized at trophoblastic cell surface, leading to the binding of β2GP1 via domain V. This binding offers a potential site of actions for aPL by changing the conformation of the protein from a circular to an open form and exposing domains I–IV to the surface [45, 46]. aPL have been incriminated in alteration of trophoblastic cells via different mechanisms. Pathogenesis of aPL in pregnancy include thrombotic mechanisms, inflammation, apoptosis and immunomodulatory molecules impairments in trophoblast [47].

#### **3.1 Thrombotic mechanisms**

The placental infarctions due to aPLs-mediated thrombosis of spiral arteries have been thought to be the main cause of fetal demise [48]. However, thrombosis of placental surface is not a universal feature. Recently, placental infarction has been demonstrated [49], only in one third of the placenta of aPLs-positive women and moreover, similar lesions were also reported in those of aPLs-negative women who had had a miscarriage [50, 51]. According to a review of 34 studies comparing the prevalence of placental features between aPL-positive women and aPLs-negative ones, five lesions, have been identified, as fingerprint of human placental aPLs including: placental

#### *Obstetric Antiphospholipid Syndrome DOI: http://dx.doi.org/10.5772/intechopen.101804*

infarction, impaired spiral artery remodeling, decidual inflammation, an increase of syncytial knots and a decrease of vasculo-syncytial membranes [52]. These different features of aPLs placenta fingerprints give rise to thought that pregnancy complications by aPLs are due to different pathologic events mainly non-thrombotic related.
