Anticoagulants. (Drugs, Pregnancy, and Lactation).

Many of the agents below have been recently approved, and for most there are no human pregnancy exposure data. But since they are often used in life-threatening situations, the maternal benefits usually far outweigh any potential fetal harm. Maternal hemorrhage and the resulting potential for fetal risk are the primary concerns when anticoagulants are used during pregnancy.

* Antithrombin III (Thrombate). This agent is indicated for patients with hereditary antithrombin III deficiency or thromboembolism and is rated pregnancy risk category B. It has also been studied as a treatment for preeclampsia, but its efficacy for this indication has not been proven. It has a high molecular weight, so it's not expected to cross the placenta. Reproductive studies in rats and rabbits at doses up to four times the human dose reveal no evidence of impaired fertility or fetal harm. Because it is prepared from pooled units of human plasma, the potential for maternal and fetal infection with an unknown infectious agent cannot be excluded.

* Thrombolytic agents. All of these agents are given intravenously. Alteplase (Activase), reteplase (Retavase), and tenecteplase (TNKase), produced with recombinant DNA technology are not teratogenic in experimental animals and are all rated C. No animal reproductive data are available for drotrecogin alfa (activated), marketed as Xigris and rated C, a genetically engineered version of activated protein C. This agent has anticoagulant and profibrinolytic effects and was approved last year for treating sepsis.

Alteplase (tissue plasminogen activator) has a very high molecular weight so it probably does not cross the placenta. It is not teratogenic in rats and rabbits, but is embryocidal in rabbits. The few reports of its use in human pregnancy, including a report of a woman with a thrombosed mitral valve prosthesis, have nor described adverse effects attributable to the drug in fetuses or newborn infants. Reteplase, which also has a high molecular weight, treats acute MI and is not teratogenic in animals but was an abortifacient in rats and rabbits.

No problems have been found in animal reproductive studies of tenecteplase, another tissue plasminogen activator similar to alteplase when single doses were used.

* Thrombolytic enzymes. The three agents in this category are anistreplase (Eminase) and streptokinase (Streptase), both rated C, and urokinase (Abbokinase). Urokinase is rated B because it is the only one of the three that has been studied in animals. At doses up to 1,000 times the human dose, no adverse fetal effects were seen in rats and mice. Several human reports indicate that it does not appear to be harmful to the fetus, although only one case early in pregnancy has been reported.

There are a lot of human data available on streptokinase: None of the reports have shown an association with congenital defects or other major risks to the fetus. No human pregnancy data are available for anistreplase.