Anticoagulants, part I. (Drugs, Pregnancy, and Lactation).

There are few or no published data describing the use of some new anticoagulants during pregnancy. For those agents, we must use other means such as the drug's chemical characteristics and experimental animal data to determine the magnitude of risk they pose to the fetus and nursing infant. In contrast there are extensive data in humans on older anticoagulants, such as heparin and coumarin derivatives, which we can use to reach conclusions about the risks they present in pregnancy and lactation.

* Heparin sodium. This agent has a high molecular weight (about 15,000 d) and does not cross the placenta or present a direct risk to the embryo or fetus. There is also no risk to the nursing infant, because transfer into milk is inhibited by the drug's molecular size and lack of oral absorption. Pregnant women on long-term heparin therapy are at risk of maternal heparin-induced osteopenia and should receive active vitamin D (calcitriol) supplements.

* Low-molecular-weight heparin (LMWH). LMWHs have a relatively high molecular weight (1,500-10,000 d), so only a small amount, if any, crosses the placenta. The American College of Obstetricians and Gynecologists has stated that LMWHs are considered at least as effective as unfractionared heparin for treatment of venous thrombosis, pulmonary embolus, or thrombophiic disorders during pregnancy but should not be used for thomboprophylaxis for pregnant women with prosthetic heart valves.

The three available LMWH products, dalteparin (Fragmin), enoxaparin (Lovenox), and tinzaparin (Innohep), and a low-molecular-weight heparinoid, danaparoid, are rated B, because animal reproduction studies have found no evidence of fetal harm. Two manufacturers have reported adverse pregnancy outcomes in women who were on these agents, but these drugs are used in highrisk maternal conditions so this is not surprising. The manufacturers of enoxapam and tinzaparin have recently cited reports of congenital anomalies in infants exposed in utero. There have also been postmarketing reports of fetal deaths.

Considering these cases together, there is no cluster of defect types, and the rate of defects does not exceed that in the general population. Adverse fetal outcomes with unfractionated heparin are also not caused by the drug.

As with unfractionated heparin, LMWHs are not expected to be excreted in breast milk.

* Thrombin inhibitors. These agents, administered intravenously are ...