The physiologic and therapeutic role of heparin in implantation and placentation

Michela Quaranta,Offer Erez,Tamar Eshkoli,Salvatore Andrea Mastrolia,Elad Leron,Gershon Holcberg,Moshe Mazor,Arie Koifman

doi:10.7717/peerj.691

Abstract

Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy.

Highlights

The use of heparins has increased since their discovery due to the number of properties and effects shared by these molecules
This study showed that, even though there were not statistical difference between the study groups, women who were treated by heparins had a higher live birth rate to that reported in literature on women with recurrent pregnancy loss (RPL); (3) The ALIFE study (Kaandorp et al, 2010) included 364 women with two or more unexplained pregnancy losses that were randomized to nadroparin 2,850 International Unit combined with aspirin 80 mg, aspirin 80 mg only, or a placebo before conception or at a maximum gestational age of 6 weeks
This effect is gained through the interaction of heparins with coagulation factors, anticoagulation proteins, their effect on the expression of adhesion molecules, matrix degrading enzymes and trophoblast phenotype and apoptosis: all important components in the process of embryonic implantation and placentation

Summary

INTRODUCTION

The use of heparins has increased since their discovery due to the number of properties and effects shared by these molecules. The effect of heparin on the inhibition of factor Xa by AT-III is dependent on the conformational change of this molecule at the heparin-binding site; the size of heparin has no importance in the inhibition of factor Xa by AT-III This effect has therapeutic implications and led to the development of a new generation of heparin derived anticoagulants including low molecular weight heparins (LMWH) and fondaparinux. LMWH are obtained as fragments of unfractionated heparin as a result of enzymatic or chemical depolymerization, yielding to molecules of mean weight of 5,000 Da (Table 1) (Weitz, 1997) while fondaparinux is a synthetic pentasaccharide based on the heparin antithrombin-binding domain (Chang et al, 2014) These medications target the anti-factor Xa activity rather than anti-thrombin (IIa) activity of AT-III, aiming to facilitate a more subtle regulation of coagulation with an. Ardeparin (Normiflo) Dalteparin (Fragmin) Enoxaparin (Lovenox) Nadroparin (Fraxiparine) Reviparin (Clivarine)

Method of preparation

Findings

CONCLUSION