By: Diana Gritsenko, PharmD Candidate 2015
Multiple complications can arise during pregnancy. While venous thromboembolism (VTE) has a prevalence rate of just 0.06% it is one of the leading causes of maternal mortality. It is recommended that at-risk pregnant women receive anticoagulation therapy for a minimum of 3 months and VTE prophylaxis for the remaining duration of pregnancy and 6 weeks postpartum.1 In June of 2014, a study assessed the potential of the direct thrombin inhibitor (DTI), dabigatran, and its prodrug, dabigatran etexilate mesylate, to cross the human placenta. Results showed that both formulations do cross the placenta and can therefore affect coagulation in the fetus. Thus, dabigatran should not be used in pregnant women.2 With one drug eliminated from the arsenal, which drugs can be used in this special population?
Anticoagulants can be administered in two ways- orally and parenterally. The oral medications include DTIs, factor Xa inhibitors, and vitamin K antagonists. The use of DTIs and factor Xa inhibitors, with the exception of argatroban and fondaparinux, is not recommended in pregnancy.1 The vitamin K antagonist, warfarin, crosses the placenta and is contraindicated in women who are pregnant (category X) unless they have a mechanical heart valve (category D). However, because of an increased risk of thromboembolism in this population, the risks associated with warfarin use (increased maternal and fetal bleeding, miscarriage, and fetal malformation) may sometimes be outweighed by the benefits. It is advised that women taking warfarin be transitioned to unfractionated heparin (UFH) or low molecular weight heparin (LMWH) 3 weeks before the planned delivery to avoid delivery trauma that can result in fetal hemorrhage.1
The heparins, both UFH and LMWH, are not absorbed orally and therefore must be given either intravenously or subcutaneously. Since they do not cross the placenta and do not result in fetal anticoagulation, these drugs are the anticoagulants of choice in pregnant women.1 LMWH is preferred over UFH for all but the final weeks of pregnancy due to its more predictable pharmacokinetic profile, obviating the need for routine monitoring.4 However, since LMWH cannot reliably be measured by activated partial thromboplastin time (aPTT), UFH is preferred in the time leading to delivery. Also, UFH is a reasonable alternative when cost is an issue or if there is a need for rapid reversal such as during delivery or perioperatively. UFH is also preferred in renal insufficiency, defined as creatinine clearance less than 30 mL/min.
If the patient has a contraindication to the use of heparins, such as a history of heparin-induced thrombocytopenia (HIT), or if the patient is unable to self-administer injections, non-heparin anticoagulants may be considered. Pregnant women can use danaparoid (not available in the United States), fondaparinux, and argatroban. Danaparoid (Orgaran®) is a low molecular weight heparinoid – a heparin derivative – that is reserved for pregnant women who have experienced acute heparin-induced thrombocytopenia.5 Fondaparinux (Arixtra®) is a direct factor Xa inhibitor. The American College of Chest Physicians suggests limiting the use of fondaparinux during pregnancy to women who have experienced HIT and were unable to receive danaparoid. Lastly, argatroban is a parenteral DTI that is recommended for patients with HIT and renal disease. Documented use of these medications in pregnancy is only available through case reports wherein all patients had discontinued UFH/LMWH after developing HIT.1
It is important to note that elective cesarean delivery is not recommended for women requiring anticoagulation. Patients and their medical teams may plan for a delivery at 39 weeks (unless otherwise indicated) in order to time the discontinuation of anticoagulants.1 The use of anticoagulants during pregnancy is challenging. There needs to be a consideration of the potential teratogenic effects, dosing complexities of the various agents, and the use of anticoagulation around the time of labor.
- Fuller KP, Turner G, Polavarapu S, Prabulos AM. Guidelines for use of anticoagulation in pregnancy. Clin Lab Med 2003; 343-356.
- Bapat P, Kedar R, Lubetsky A, Matlow JN, Aleksa K,Berger H, et al. Transfer of Dabigatran and Dabigatran Etexilate Mesylate across the dually perfused human placenta. Obstetrics & Gynecology 2013; 123(6); 1256-1261.
- Coumadin (warfarin)[package insert]. Princeton, New Jersey; Bristol-Myers Squibb; revised October 2011.
- Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005; 106:401.
- Orgaran (danaparoid)[package insert]. Kirkland, Quebec; Merck; Revised April 2011.
- Arixtra (fondaparinux sodium)[package insert]. Research Triangle Park, NC; GlaxoSmithKline; Revised September 2013.
[pubmed_related keyword1=”anticoagulation” keyword2=”pregnancy” keyword3=”women”]