The role of heparin in the prevention of preeclampsia

The etiology of preeclampsia is unknown, but one of the pathogenetic mechanisms of disease appears to involve the uteroplacental circulation thrombosis. Preeclampsia occurs in 5-8% of pregnancies with an increased frequency in the first pregnancy. The frequency of preeclampsia in second pregnancy is less than 1% in normotensive women during the first pregnancy, while the occurrence of preeclampsia is reported at 15-18%. The occurrence of severe preeclampsia in previous pregnancy carries the risk of recurrence of 47%, and if it had appeared in the 2nd trimester, increasing to 65%. Over the past 20 years the scientific community has tended to consider whether thromboprophylaxis with anti-platelet agents could improve the outcome of pregnancy in patients at risk of preeclampsia. With the gradual recognition of the association between congenital thrombophilic disorders and poor outcome of pregnancy interest in the use of heparin has taken value in the field of obstetrics. Some authors have speculated that the low-pressure intervillous flow in the presence of a maternal hypercoagulable state associated with trophoblastic dysfunction, can stimulate excessive fibrin deposition in placental vessels resulting in infarction of the trophoblast and placenta, these all features of the pathophysiology of preeclampsia. Moreover, recent works report that women with preeclampsia showed a higher inflammatory response compared to women with physiological pregnancy. During the first and second trimester, the risk of preeclampsia was correlated with an increase in serum markers of inflammation as some TNF-α, IL-2, vascular adhesion molecules and activation of leukocytes . The potential benefit of heparin in this condition may be related to the supposed anti-inflammatory action of the drug related to its ability to reduce the level of those molecules. Moreover, given the association between preeclampsia and increased inflammatory reaction, as well as the interaction between inflammation and clotting cascade, one might assume that, by regulating the two pathological processes together, we can expect a more favorable outcome of pregnancy. These could be the reason why a controlled historical study has shown a better outcome in the group treated with low-dose aspirin combined with fractionated heparin compared with the group treated only with aspirin in patients with a history of preeclampsia, regardless of the state that thrombophilia was not performed. The purpose of this prospective randomized protocol is to determine whether the association low-dose aspirin / fractionated heparin can improve the outcome of pregnancy in women with a history of severe preeclampsia, low birth weight and fetal growth restriction.