The Role of Anticoagulant Therapy in the Prevention of Preeclampsia Pharmacokinetic and pharmacodynamic mechanisms

Abstract

Pregnancies complicated with preeclampsia associate a high incidence of intrauterine fetal death, intrauterine growth restriction, premature ruptures of membranes, abruption placentae and prematurity. Understanding the pathogenesis of preeclampsia is mandatory for a correct approach and prevention management of high risk cases. Placental hypoperfusion seems to be a key factor in developing systemic resounding. By placental necrosis and apoptosis, cell-free DNA is released in maternal circulation in early pregnancy, respectively prior 17 weeks of gestation. There is no test, useful in early pregnancy, accurate enough to predict preeclampsia. Various screening test have been proposed in order to predict the development of preeclampsia, but most of them are not sufficiently accurate for general screening. There is a continuous debate regarding the algorithm of administration, doses and timing of low dose aspirin. The initiation moment is crucial, as the administration after the development symptoms and signs of preeclampsia do not interfere with the progression and the severity of the disease. Early initiation of therapy with low dose aspirin, prior the end of the first trimester is important since the pathogenesis mechanisms of preeclampsia take place in the first trimester. The action of acetylsalicylic acid consists in inhibition of COX-1 and COX-2 (cyclooxygenase isoenzymes), necessary for prostaglandin biosynthesis. Preferential inhibition of Thromboxane A2 by low dose aspirin, counterbalance the increased production of thromboxanes characteristic to preeclampsia and modulate the inflammatory process, amplified in pregnant women with preeclampsia.