Page 57 - Pro-active Management of Women’s Health after Cardiometabolic Complicated Pregnancies

2.2 Associations between phenotypes of preeclampsia and thrombophilia| 55
The most important strength of this study is the high number of cases, which enabled comparisons between preeclampsia phenotypes.
Overall, severe preeclampsia is associated with anti-phospholipid antibodies. This is mainly explained by the association with placental insufficiency (placental infarction and IUGR), but not with HELLP syndrome. We hypothesize that this is due to the fact that this thrombophilic factor does not act through systemic coagulation pathways, but at the placental side. Ernst et al report on the pathophysiologic mechanisms of anti-phospholipid syndrome140. The primary hypothesis is that anti phospholipid antibodies cause placental thrombosis, leading to placental infarction. The associations we found between anti phospholipid antibodies and placental infarctions, impaired fetal growth and deliveries before the 34th gestational week confirm this hypothesis, since the one phenotype is very likely to result from the other.
One acting mechanism might be through Beta-2GP1 molecule, present on the surface of trophoblastic cell membranes. It appears to inhibit thrombosis by reducing the conversion of Prothrombin to thrombin on platelets and inhibiting the activation of the intrinsic coagulation cascade140. Beta-2GP1 antibodies block the Beta-2GP1 molecule, so it can no longer inhibit thrombosis. Another acting mechanism might be the disruption of annexin V, that normally binds to the phospholipid molecules on the surface of the trophoblastic membrane, preventing thrombosis by forming a protective protein coat.
In 2012 the FRUIT-study, a randomized controlled trial studying the effect of low-molecular weight heparin on recurrence risk of preeclampsia in women with thrombophilia, suggests that if inheritable thrombophilia like Protein-S deficiency are present, administration of aspirin and low molecular weight heparin during a next pregnancy may decrease the recurrence risk141. Studies measuring the effect of low-molecular weight heparin on the recurrence risk of