Clinical manifestations

Vascular thrombosis

Thrombosis lies at the core in symptoms of APS. The most significant and exclusive characteristic of thrombosis in APS is that patients present arterial as well as venous thrombosis. Any tissue and organ can be involved, but common thromboses are deep venous thrombosis (DVT) of lower limbs, pulmonary embolism and cerebral ischemic attack. The prevalence of thrombosis varies among racial backgrounds, and arterial thrombotic events have been shown more in Japanese patients with APS compared to in white patients. Positivity for LA, triple aPL positivity and persistent positivity for aCL at medium to high titres are related to the risk of developing thrombosis.

Cerebral vessels are the site of predilection for the arterial thrombosis, accounting for more than 90%, while ischemic cardiac events occur relatively infrequently. APS is recognized as a most important causative disease of early-onset cerebrovascular thrombosis such as strokes and transient ischemic attacks (TIAs). Other organs include the eyes (retinal arteries), abdomen (mesenteric arteries), and digital and limbs (peripheral arteries) are affected. Thrombosis usually remains local, excepting catastrophic antiphospholipid syndrome (CAPS), but it is often recurrent.

The DVT of lower limbs occurs most frequently (∼40%), and superficial leg vein thrombosis also occurs (∼12%). Pulmonary thromboembolism accompanying DVT or even solely has been often presented. While rare, other venous thromboses related to APS are axillary venous thrombosis, retinal vein thrombosis, renal vein thrombosis, Budd–Chiari syndrome (hepatic veno-occlusive disease), cerebral venous thrombosis (sagittal sinus thrombosis), or adrenal vein thrombosis. Budd–Chari syndrome may be the first clinical manifestation of APS.

Pregnancy morbidity

Obstetric manifestations are the defining characteristics of APS. Recurrent pregnancy loss, occasionally in the second trimester, is classic and characteristic feature of APS. Recently, obstetric APS have been recognized as different from thrombotic APS. Current evidence demonstrates that fetal loss and severe preeclampsia or placental insufficiency are associated with APS. However, the association between recurrent early pregnancy loss (prior to 10 weeks of gestation) and aPL remains inconclusive.

The most frequent fetal complication in APS is recurrent pregnancy loss. Between 7% and 25% of recurrent pregnancy loss is owed to the presence of aPLs. Secondary APS, the history of both thrombosis and pregnancy morbidity and triple aPL positivity, and reduced complement levels are reportedly associated with pregnancy failure in patients with APS. The treatment of APS patients with anticoagulant or antiplatelet agents shows remarkable improvement in live birth rates. Expecting women with APS have the likelihood of live birth of almost 80% with proper management, compared with only 15% of patients without treatments. Babies bone to mothers with APS exhibit little tendency to develop thrombosis or lupus, despite the aPLs from mothers were transferred to the babies across the placenta.

On the other hand, even with anticoagulant or antiplatelet treatment, the risk of other obstetric morbidities, such as preeclampsia, intrauterine growth restriction (IUGR), and prematurity remains high. Premature birth occurs as the common neonatal complication of APS, as a consequence of preeclampsia, IUGR and hemolysis, elevated liver enzyme levels and low platelet levels (HELLP) syndrome. As for fertility, available evidence suggests that aPL is not a mediator of infertility, and aPL positivity does not seem to influence in vitro fertilization outcomes.

Multiple mechanisms likely contribute to obstetric manifestation in APS. Initially, thrombotic predisposition has been simply sought to induce placental events in APS, although the evidence of thrombosis of the uteroplacental vasculature was invalid. APLs might disrupt trophoblast invasion and endometrial angiogenesis, and consequently, lead to placental dysfunction. Studies have demonstrated the complement activation by aPL has a responsible role. The activation of complement by aPL, both classical and alternative pathways, may cause feral loss, IUGR, and preeclampsia. Blood flow in the uterine arteries by Doppler ultrasonography on second trimester is regarded as a predictor of development of placental insufficiency, preeclampsia.