The Effects of Antenatal Anticoagulants (Low-Molecular-Weight Heparin and Aspirin) on Neonatal Pulmonary Vasculature in Rabbits

Abstract

Low-molecular-weight heparin and aspirin are the most prescribed medical agents as anticoagulants in pregnancy. Our objective was to investigate the effects of antenatal use of low-molecular-weight heparin and aspirin on pulmonary vascular development in neonatal rabbits. Seven pregnant rabbits (42 newborn rabbits) were divided into 5 groups as follows: control group (group 1, n = 14), heparin treated (group 2, n = 8), heparin and aspirin treated (group 3, n = 7), only aspirin treated (group 4, n = 6), and high-dose heparin treated (group 5, n = 12). Pulmonary histologic evaluations were carried out for all groups. Angiogenesis was also tested by CD34 immunostained microvessel count (mvc). Pathologic examination of pulmonary vasculature revealed that pulmonary vascular thickening occurred at the level of alveoli in heparin-, heparin- and aspirin-, and high-dose-heparin-treated groups (groups 2, 3, and 5). The percentage of wall thickness was different in groups 2 (26%), 3 (28.2%), and 5 (30.8%) compared with group 1 (21.4%). Statistical differences were observed between group 1 vs 2, 3, and 5. Microvessel count was also different between groups 2 (mvc = 90.5), 3 (mvc = 90.2), and 5 (mvc = 96.3) vs group 1 (mvc = 86.7). The microvessel count was statistically different between groups that received low-dose heparin vs high-dose heparin. Antenatal administration of low-molecular-weight heparin showed an effect on pulmonary vascular development. This effect may be explained by the influence of heparin on angiogenesis through placental growth factors. Further experiments are needed to understand the pathophysiology of these findings, and clinical studies are needed to correlate of these results.