Warfarin is teratogenic and causes miscarriage, stillbirths, and fetal malformations. In one study of 71 women given warfarin throughout pregnancy, the rates of miscarriage were 32 percent; stillbirth, 7 percent; and embryopathy, 6 percent (Cotrufo, 2002). The risk was highest when the mean daily dose of warfarin exceeded 5 mg. Similarly, the American College of Cardiology and the American Heart Association estimate that the risk of embryopathy is dose dependent, with a lower risk-less than 3 percent-if the dose of warfarin is :;5 mg/d (Nishimura, 2014). If the dosage is >5 mg/d, the risk of embryopathy exceeds 8 percent.
Anticoagulation for mechanical valves using low-dose unfractionated heparin is definitely inadequate and carries a high associated maternal mortality rate (Chan, 2000; Iturbe-Alessio, 1986). Even ful anticoagulation with either unfractionated heparin (UFH) or one of the low-molecular-weight heparins (LMWH) is associated with valvular thrombosis (Leyh, 2002, 2003; Rowan, 2001). But, compliance with twice-daily dosing and therapeutic monitoring may have contributed (McLintock, 2014). hus, if full anticoagulation with dose-adjusted UFH or LMWH is used, meticulous monitoring is recommended. The activated partial thromboplastin time (aPTT) should be at least 2 times control or anti-Xa levels should be 0.8 to 1.2 U/mL at aData from the Registry of Pregnancy and Cardiac Disease. Data from van Hagen, 2015.
4 to 6 hours postdose (Nishimura, 2014).
Several diferent treatment options-none of which are completely ideal-are principally based on consensus opinion. Two are from the American College of Chest Physicians and the other jointly from the merican College of Cardiology and the American Heart Association (Bates, 2012; Nishimura, 2014). Any of four regimens is recommended. First, adjusted-dose LMWH is given twice daily, with a peak anti-Xa level drawn 4 hours ater dosing. In another, adjusted UFH is dosed every 12 hours to keep the midinterval aPTT twice control or anti Xa level between 0.35 0.70 U/mL. As a third option, LMWH or UFH is given as just described until 13 weeks, and then warfarin is substituted until near delivery, at which time it is replaced by LMWH or UFH. Last, in women judged to carry a high risk of thrombosis and for whom the eicacy and safety of heparins are concerns, warfarin is suggested throughout pregnancy. Heparin is then substituted close to delivery. In addition, aspirin, 75 to 100 mg, is given daily.
Heparin is discontinued just before delivery. If delivery supervenes while the anticoagulant is still efective, and extensive bleeding is encountered, then protamine sulfate is given intravenously. nticoagulant therapy with warfarin or heparin may be restarted 6 hours following vaginal delivery, usually with no problems. Following cesarean delivery, full anticoagulation is withheld, but the optimal duration is not exactly nown. The American College of Obstetricians and Gynecologists (2017) advises resuming unfractionated or low-molecular-weight heparin 6 to 12 hours ater cesarean delivery. It is our practice, however, to wait at least 24 hours following a major surgical procedure.