Pregnant Woman Who Is Heterozygous for Factor V Leiden

A 24-year-old woman who is 14 weeks pregnant with her first child is heterozygousfor factor V Leiden. The patient is healthy, has no chronic medical conditions,and takes no long-term medications.HISTORY
Five years earlier, the patient's older brother sustained a deep venousthrombosis (DVT) with pulmonary embolism when his leg was immobilizedafter minor arthroscopic surgery of the knee. His workup for hypercoagulabilityrevealed factor V Leiden; subsequently, the rest of the family was tested.PHYSICAL EXAMINATION AND LABORATORY RESULTS
Physical examination, hemogram, and chemistry panel are normal. Prothrombintime and partial thromboplastin time are also normal.Which strategy is most appropriate for this patient?A. Initiate aspirin, 325 mg/d, and continue for the full term of the pregnancy.B. Initiate warfarin and titrate dosage to achieve an INR of 2 to 3; continuefor the full term of the pregnancy.C. No therapy is indicated because the patient is an asymptomatic carrier;she needs only careful observation.D. Initiate daily subcutaneous administration of heparin, and continue forthe full term of the pregnancy.CORRECT ANSWER: DThis patient is heterozygous for the most frequently diagnosedhereditary hypercoagulability disorder-factorV Leiden. Although not nearly as common in the geneticallyheterogeneous American population as in morehomogeneous European populations, factor V Leiden accountsfor about20% of diagnosesthat result fromhypercoagulabilityworkups.¹Factor V Leidenis more commonamong Causasiansand is veryrare among personsof Africanor Asian descent.The managementof patientswho areheterozygous forfactor V Leidencontinues toevolve. However,there is generalagreement thatasymptomaticcarriers do notrequire anticoagulation,becauseat least half ofdocumented heterozygotes will never experience DVT. Inthis setting, the risk-benefit ratio favors observation.However, the risk-benefit ratio changes when independentrisk factors for DVT are present. These include:

• Prolonged surgery with general anesthesia.
• Orthopedic injury that results in splinting/casting andimmobility (as was the case with this patient's brother).
• Pregnancy.

Under these circumstances, the threat of thromboembolismescalates and prophylactic anticoagulationis indicated until the patient is no longer at increasedrisk.

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Most authorities recommend prophylactic anticoagulationfor the duration of the pregnancy and during thepuerperium, when the thromboembolic risk remains elevated.Others might confine treatment to the last trimesterand the puerperium, when the incidence of venous thromboembolismis highest. In any event, observation only(choice C) is insufficient. The question that remains is:what is the optimal prophylactic regimen?Aspirin (choice A) is not appropriate for a patientwho is heterozygous for factor V Leiden. Anticoagulantsare indicated for such patients, not antiplatelet agents. Aspirinhas a role in the treatment of anticardiolipin syndrome-which is associated with such complications ofpregnancy as thromboembolism and recurrent miscarriages-but it has no place in therapy for factor V Leiden.Warfarin (choice B) is a well-established anticoagulantand could be used in the other settings that increasethe risk of DVT in patients with factor V Leiden. (This isalso true for those who are heterozygous for other hereditaryhypercoagulable disorders, such as antithrombin III,protein C, and protein S deficiency.) However, warfarincrosses the placenta and heightens the risk of hemorrhagein the fetus. More important, warfarin is teratogenic;it caused birth defects in up to 25% of infants whosemothers took the drug.

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Thus, it is absolutely contraindicatedhere.That leaves heparin (choice D). Studies have shownthat heparin does not cause hemorrhagic complications ineither the mother or the fetus during pregnancy or at delivery

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;moreover, it is not teratogenic. These studies havealso demonstrated the efficacy of heparin in preventingthromboembolism in pregnant women at risk. Standard,unfractionated heparin has been widely used, but lowmolecular weight forms seem at least as effective and areconvenient to administer, because they can be given in aweight-adjusted dosage and laboratory monitoring is notrequired.