Anticoagulation for Mechanical Heart Valves During Pregnancy

This article was collaboratively written with Klaudia Froncz, a fourth-year PharmD candidate at Chicago State University College of Pharmacy.

The search for the ideal anticoagulant in pregnant women with mechanical heart valves (MHV) is still ongoing. Preferably, it would be an agent that does not cross the placenta, is associated with the lowest rate of thromboembolic complications (TECs) and mortality, and does not need intensive monitoring.¹ Unfortunately, there are no available anticoagulants that meet all these criteria, and finding a balance between adequate anticoagulation of the mother and safety of the fetus is a difficult challenge in clinical practice today.

Pregnant women with MHV are at high risk of maternal morbidity and mortality, with only a 58% chance of experiencing an uncomplicated pregnancy that results with live birth.² Because of the prothrombotic state of pregnancy, there is an increased risk of thromboembolic events for this patient population. As a result, all pregnant women with MHV require therapeutic anticoagulation throughout the pregnancy. It is well known that in non-pregnant patients with MHV, the anticoagulant of choice is a vitamin K antagonist (VKA), which is associated with the lowest mortality and TEC rates.³ However, its fetal adverse effect profile possesses a challenging dilemma with regards to use in pregnancy.

There are currently no controlled trials to guide anticoagulation therapy in pregnancy and as a result no optimal therapy exists. The 3 commonly used regimens in practice include: VKAs throughout pregnancy, low molecular weight heparin (LMWH) or unfractionated heparin (UFH) throughout pregnancy, and sequential treatment consisting of LMWH in the first trimester followed by VKA administration in the second and third trimesters.⁴ All of these regimens have their own pros and cons, and none of them comes without maternal or fetal risk. VKAs, such as warfarin, have a more favorable maternal risk profile having the lowest rates of TECs and mortality.⁵ However, they are able to cross the placenta and cause fetal development complications. These complications include warfarin embryopathy, which occurs in the first trimester and warfarin fetopathy occurring in later trimesters. Warfarin embryopathy refers to hypoplasia of the nasal bridge, congenital heart defects, agenesis of the corpus callosum, and growth retardation.⁶ Whereas, warfarin fetopathy is associated with nervous system and ocular abnormalities, fetal loss, and stillbirth.⁵

Additionally, there’s a risk of fetal intracranial bleeding if the pregnant patient takes warfarin in the weeks prior to delivery. Heparins are associated with higher rates of maternal cardiac complications and TECs during pregnancy. This can be due to variety of reasons such as changing dose requirements, difficulties in monitoring, and patient compliance. Nonetheless, these agents do not cross the placenta; therefore, they possess less fetal risk than warfarin. LMWH is preferred over UFH due to its more predictable anticoagulant effect, and as a result, its utilization for this indication has increased in the United States. Lastly, sequential treatment was designed to minimize the harmful effects of warfarin on the fetus. This treatment approach can potentially avoid the risk of warfarin embryopathy, but does not prevent warfarin fetopathy and all of its adverse outcomes. Conversely, sequential treatment is associated with a more favorable maternal risk profile.

The 2014 ACC/AHA guidelines for the management of patients with valvular heart disease provide recommendations for anticoagulation in patients with MHV and specifically address management in pregnant patients.³ It is important to note that these recommendations are based mostly on small retrospective data. These guidelines advise to continue taking warfarin during pregnancy if the dose is ≤ 5 mg/day. For patients taking warfarin at doses > 5 mg/day and those who refuse to take VKAs, it is recommended that warfarin be discontinued during the first trimester and replaced by either dose-adjusted LMWH at least 2 times per day (with a target anti-Xa level of 0.8-1.2 U/mL) or dose-adjusted continuous infusion of UFH (with aPTT at least two times control). The guidelines also recommend that warfarin be used during the second and third trimesters. Approximately two weeks before the anticipated date of delivery, warfarin should be changed to UFH to avoid the potential of maternal and fetal bleeding. In addition to taking warfarin in the second and third trimesters, patients are also advised on taking low-dose aspirin. The continuation of aspirin use during the time of delivery should be discussed by the medical team due to possible need of epidurals and risk of bleeding. Two recent meta-analyses evaluated anticoagulation regimens in pregnant women with MHV.^1,6 Both studies found outcomes which continue to support the recommendations from the guidelines.

Currently, there is no ideal anticoagulant for pregnant women with MHV, as a result the sequential treatment approach is most commonly utilized. The competing interests of the mother and fetus make the determination of which anticoagulant to utilize extremely challenging. Decisions should be individualized after a thorough discussion with patient about the risks and benefits of each therapy. Lastly, further research is needed to investigate different anticoagulation approaches in pregnant patients.

References

• Steinberg ZL, Dominguez-Islas CP, Otto CM, Stout KK, Krieger EV. Maternal and fetal outcomes of anticoagulation in pregnant women with mechanical heart valves. J Am Coll Cardio. 2017;69(22):2681—2691.
• Van Hagen IM, Roos-Hesselink JW, Ruys TP, et al. Pregnancy in women with a mechanical heart valve: data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC). Circulation. 2015;132:132—142.
• Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease. J Thorac Cardiovasc. Surg. 2014;148(1):e1-e132.
• McLintock C. Thromboembolism in pregnancy: challenges and controversies in the prevention of pregnancy-associated venous thromboembolism and management of anticoagulation in women with mechanical prosthetic heart valves. Best Pract Res Clin Obstet Gynaecol. 2014;28(4):519-536.
• D'Souza R, Silversides CK, McLintock C. Optimal anticoagulation in pregnant women with mechanical heart valves. Semin Thromb Hemost. 2016;42(7):798-804.
• Xu Z, Fan J, Luo X, et al. Anticoagulation Regimens During Pregnancy in Patients With Mechanical Heart Valves: A Systematic Review and Meta-analysis. Can J Cardiol. 2016;32(10):1248.e1-9.