OAPS/MOAPS

OAPS/MOAPS

When inflammation and /or thrombosis occur in the placenta, it is associated with poor obstetrical outcomes, mainly, recurrent first trimester abortion and/or fetal losses. Though aPL related thrombosis have been the main mechanism related to these obstetric complications, some questions concerning this theory are still present. Nowadays, it seems possible to recognize different mechanisms to explain different complications related to aPL (3)(Table 1). Boton que abra la table 1 Clinically, we think an agreement exists in the recognition of distinct subsets of APS in some patients, the aPL-related injury is only present as venous thromboembolic phenomena; in others as an arterial occlusion alone; in a third subgroup, the only and often recurrent, bad obstetrical outcomes and, in the end, a fourth subset of patients that may have a combination of the above mentioned clinical events (4,5). Both non-thromboembolic pulmonary and obstetric complications related to aPL may be good examples of possible non-primary thrombotic, mainly inflammatory manifestations related to aPL or APS (6)

Pregnancy losses are the main obstetrical complications of the so-called obstetric antiphospholipid syndrome (OAPS). As we commented before, classically, they have been strongly attributed to placental thrombosis and further placental infarcts. But in some cases it is not possible to show evidence of decidual or placental thrombosis (7, 8). On contrary, some cases showed inflammatory histophatologic signs without evidence of underlying infection. Some cases of women suffering from OAPS, have low plasma C3 and/or C4 levels (9, 10). aPL antibodies, mainly b2-glycoprotein-I/anti-b2-glycoprotein-I complexes may activate both, classical and alternative complement pathways provoking fetal loss (11). This complement pathway activation may be reverted by heparins, preventing pregnancy loss (12). On the other hand, TF expression is dependent on complement activation and neutrophils, notably as a result of C5a-C5aR interaction (13). In the same way, TF expression in monocytic cells may amplify this proinflammatory loop. Thus, direct trophoblast cells injury due to complement attack-complex or by means of the increase of neutrophilic oxidative burst may ultimately provoke fetal death. Additionally, TF up-regulation may activate coagulation pathway with the apparition of further thrombosis (14). Furthermore, complement activation products may cause negative imbalance of angiogenic factors required for appropriate placentation and normal pregnancy development (15). It has also been demonstrated that C5a-C5a-R interact directly triggering the release of sFlt-1 from myeloid cells which may alter the balance between  angiogenic and anti-angiogenic factors in pregnancy and predispose and facilitate the pregnancy complications related to aPL or APS (16). Clinically, the prevalence of systemic thrombosis in OAPS patients is low (4,16). Some pregnant women diagnosed as having OAPS have low or low-normal plasma C4/C3 levels (9,10). Likewise, from a clinical point of view these seems to exist a profile of aPL-related manifestations notably obstetrics, different to “classical” –thrombotic- APS (16). OAPS will be preferably characterized by bad obstetric outcomes, mainly, recurrent first trimester abortion and/or fetal loss. Other complaints, such preeclampsia, abruptio placenta and  premature births are also well known. Fortunately, the current recommended treatment with heparin and low-aspirin dose covers both, anti-thrombotic and anti-inflammatory lesions arms.

The clinical and serological heterogeneity of the APS in general and of the OAPS in particular, make it difficult to compare results. Several published papers lack clear definition of exact obstetric morbidity, recurrent first trimester abortions, fetal loss or premature births related to placental injury or mixed cases. In the same way, most papers lack specific information about the laboratory classification related to the type of aPL (ie: I, IIa, IIb or IIc) (2). Besides other clinical and laboratory data are inconstant or lacking, for instance: BMI, smoking habit, race, prior obstetric background, course of aPL during pregnancy, inherited thrombophilic studies, complement levels or, non-standard aPL determination. On the other hand, standardization of laboratory methods other than LA and aCL are lacking. Besides, new pathological evidences related to obstetric involvement seem to define a possible variant to classic APS. The hypothesis of dual different mechanisms of action in the isolated OAPS, which are related to a specific gestational age (pre-embryonic, embryonic, fetal…) which, by itself, supposes a different target; for instance, extravillous cytotrophoblast first, syncytiotrophoblast afterwards, coinciding with the beginning of the uteroplacental circulation (>7-8 weeks) and ending with the definitive mature placental (inflammation related to innate immune-cells first, and finally mixed, inflammatory and thrombotic). (More inflammation/less thrombotic in earlier pregnancy loss; less inflammatory/more thrombotic or similar in latest pregnancy complications) (17).


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