Placental transport of low molecular weight heparin in the pregnant sheep

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Abstract
Standard heparin, an effective treatment for antepartum thromboembolic disease, is thought to be safe for the fetus since it does not cross the placenta. Recently, a number of low MW heparins were prepared which were shown to produce less bleeding than standard heparin for an equivalent antithrombotic effect in experimental animals. The low MW heparins may also provide superior antithrombotic therapy in antepartum thromboembolic disease. It is not known whether the low MW heparins cross the placenta. To determine this, the pharmacokinetics of 125I-labeled standard heparin and a low molecular weight heparin, and their anticoagulant effects in mother and fetus were examined using a pregnant sheep model. Catheters were inserted into maternal and fetal femoral arteries at 108-119 d [days] gestation (term: 147 d). 1-3 days later the mothers were given a bolus i.v. injection of 5000 anti-Xa U of 125I-labeled standard heparin or low MW heparin, CY 222. Nine serial blood samples were collected over 4 h from both mother and fetus for measurements of radioactivity, anti-Xa activity (chromogenic) and activated partial thromboplastin times. When therapeutic levels of standard and CY 222 heparins were achieved in the mother, there was no detectable radioactivity or anticoagulant effect in the fetus. Standard heparin and the low MW CY 222 do not cross the placenta in the pregnant sheep.

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