Clinical twisters: Pregnancy complicates therapy

A 35-year-old patient, C.A., with a mechanical heart valve, has had an INR of 2.5 to 3.5 for several years while on warfarin therapy. Today, at her visit to your anticoagulation clinic, she confides that she is six weeks' pregnant. What do you do?

I would counsel C.A. that although anticoagulant therapy is indicated during pregnancy in patients with mechanical heart valves for the prevention of venous thromboembolism, there are potential risks of taking warfarin therapy while pregnant. The risk to the fetus would include bleeding and teratogenicity. I'd emphasize, however, that there is considerable evidence that embryopathy occurs only between the sixth and 12th weeks of gestation.

I would counsel her to speak to her physician about the use of low molecular weight heparin (LMWH) anticoagulant therapy as a safer alternative during the sixth to 12th weeks since these drugs do not cross the placenta. I'd also counsel her that although heparin or LMWH is considered safer for the fetus than warfarin, it has been associated with an increased risk of valve thrombosis, major bleeding complications, and death compared with oral anticoagulant therapy in women with prosthetic heart valves.

Cynthia G. Villarreal, Pharm.D., R.Ph.Shriners Burns HospitalGalveston, Texas

Warfarin crosses the placenta (pregnancy category X), and it has teratogenic effects leading to fetal malformations, especially if used during weeks six to 12 of pregnancy. As this patient is now six weeks' pregnant, warfarin should be discontinued immediately. An alternate anticoagulant such as unfractionated heparin (UFH) (pregnancy category C) or LMWH (pregnancy category B) given in full treatment doses should be initiated and continued throughout pregnancy.

A third option, also supported by current guidelines, would be to reinstitute warfarin therapy after week 13 of pregnancy; however, we do not favor this approach, as the risk of intracranial hemorrhage in the fetus (regardless of delivery route) is extremely high. Despite some recent controversy involving a warning in the package insert of enoxaparin (regarding safety in pregnant patients with mechanical heart valves), subsequent reports and consensus statements agree that available data for LMWHs suggest similar, if not better, outcomes than UFH.

In this patient, we recommend initiating enoxaparin at a dose of 1 mg/kg subcutaneously b.i.d. A twice-daily dosing regimen of LMWH is preferred, as the half-life of LMWH is shorter in pregnancy. Anti-factor Xa activity monitoring should be performed every one to two weeks throughout pregnancy, with peak levels aimed at > 1 IU/ml (preferably 1-1.2 IU/ml) and trough levels aimed at > 0.5 IU/ml. We favor using a LMWH over UFH as it has a better side-effect profile and a more predictable anticoagulant effect.

Linda Leav, Pharm.D. candidate (2006) The University of Illinois at Chicago College of Pharmacy

Edith A. Nutescu, Pharm.D. Clinical Associate Professor Director Antithrombosis Center
The University of Illinois at Chicago
College of Pharmacy & Medical Center