**5. Risk stratification in obstetric antiphospholipid syndrome**

The outcome of pregnancy in women with APS depends on their clinical history and aPLs profile. Therefore, women with APS or high levels of aPLs should be counseled before pregnancy to perform risk stratification.

Several risk factors are predictors of poor pregnancy outcome. The presence of triple aPL positivity [72, 73], which refers to IgG/IgM aCL plus IgG/IgM anti-β2GPI plus LA, correlates strongly with vascular thrombosis and pregnancy morbidity. Moreover, the presence of persistent positive LA [74, 75] has been reported as the strongest predictor for either pregnancy loss or recurrent thrombosis. These high-risk aPL profiles (**Table 2**) are associated with an increased risk of pregnancy morbidity such as intrauterine growth restriction and premature birth as well as pre-eclampsia despite appropriate anticoagulant treatment [73, 76–78]. Regarding clinical features, women with aPLs and a history of thrombosis, severe pregnancy complications such as pre-eclampsia, eclampsia, or HELLP syndrome, a concomitant SLE diagnosis, or low complement levels are associated with a higher risk of pregnancy morbidity [78, 79]. On the other hand, there are consistent data showing that a history of pregnancy morbidity alone and a single aPLs positivity for aCL or anti-β2GPI are associated with a higher live birth rate [73].

According to the risk stratification, women with obstetric APS can be divided into three groups (**Figure 1**), namely A-low risk pregnancy, those with obstetric morbidity alone and single or double positivity for aPL, B-medium risk pregnancy, those with prior thrombosis and single or double positivity for aPL, and C-high risk pregnancy, those with prior thrombosis and/or severe pregnancy complications and LA/triple positivity for aPL. This subdivision could guide the therapeutic approach in these patients.

Pregnant women with APS must also be closely monitored during pregnancy to promptly identify signs of placental insufficiency. It has been shown that upgrading therapy at the first signs of placental insufficiency results in a higher birth rate [80].


*aPLs: antiphospholipid antibodies, LA: lupus anticoagulant, aCL: anti-cardiolipin antibodies, anti-*β*2GPI: anti*β*2glycoprotein I, IgG: immunoglobulin G, IgM: immunoglobulin M.*

#### **Table 2.**

*Definition of high-risk and low-risk antiphospholipid antibodies profile.*

#### **Figure 1.**

*Risk stratification and management of antiphospholipid pregnancies. aPL: antiphospholipid antibodies, LDA: low dose aspirin; IVIG: intravenous immunoglobulin; PE: plasma-exchange; HCQ: hydroxychloroquine.*

Abnormal uterine artery flow on Doppler ultrasound is an indirect indicator of the development of placental insufficiency and/or pre-eclampsia [81]. Therefore, the European Alliance of Associations for Rheumatology, (EULAR) guidelines recommend the use of uterine artery Doppler ultrasonography for the management of SLE/APS patients [82]. In addition, a drop in platelet count in the first trimester has recently been found to be associated with the development of pre-eclampsia in APS pregnancy compared to non-APS pregnancies. APS women who later developed pre-eclampsia and/or placental insufficiency had a decrease in initial platelet count of more the 20% (personal observation, not published).
