LMWHs available for use in pregnancy include enoxaparin, tinzaparin, and dalteparin. Enoxaparin (Lovenox) pharmacokinetics were studied in 36 women with TE during pregnancy or immediately postpartum (Rodie, 2002). he dose was approximately 1 mg/kg given twice daily based on early pregnancy weight. Treatment was monitored by peak anti-factor Xa activity at 3 hours postinjection, with a target therapeutic range of 0.4 to 1.0 U/mL. In 33 women, enoxaparin provided satisfactory anticoagulation. In the other three women, dose reduction was necessary. None developed recurrent thromboembolism or bleeding complications. In postcesarean women with a body mass index (BMI) �35, Stephenson and associates (2016) found that weight-based dosing of enoxaparin 0.5 mg/kg twice daily more efectively achieved prophylactic peak anti-Xa levels between 0.2 to 0.6 U/mL than a ixed dose of 40 mg daily. Similar indings were reported by Overcash and colleagues (2015).
For tinzaparin (Innohep), a dosage of 75 to 175 U/kg/d was necessary to achieve peak anti-factor Xa levels of 0.1 to 1.0 U/mL (Smith, 2004). In studies of dalteparin (Fragmin) pharmacokinetics, conventional starting doses of dalteparin-100 U/kg every 12 hours-were likely insuicient to maintain ull anticoagulation (Barbour, 2004; Jacobsen, 2003). Thus, slightly higher doses than that shown in Table 52-5 may be required.
Standard prophylactic and therapeutic dosages recommended by the American College of Obstetricians and Gynecologists (2017b) for various L\1WHs are listed in Table 52-5. Whether such dosages require adjustments during the course of pregnancy is controversial (Berresheim, 2014; Cutts, 2013). Some suggest periodic measurement of anti-factor Xa levels 4 to 6 hours after an injection with dose adjustment to maintain a therapeutic level. Large studies using clinical end points that demonstrate an optimal therapeutic range or show that dose adjustments increase therapy safety or eicacy are lacking. Accordingly, the American College of Chest Physicians and others note that routine monitoring with anti-Xa levels is difficult to justiy (Bates, 2012; McDonnell, 2017).
Early reviews concluded that LMWHs were safe and efective (Lepercq, 2001; Sanson, 1999). Despite this, in 2002, the manufacturer of Lovenox warned that its use in pregnancy had been associated with congenital anomalies and a higher risk of hemorrhage. Ater its own extensive review, the American College of Obstetricians and Gynecologists (20 17b) concluded that these risks were rare, that their incidence was not higher than expected, and that no cause-and-efect relationship had been established. It further concluded that enoxaparin and dalteparin could be given safely during pregnancy. Other reports confirm their safety (Andersen, 2010; Bates, 2012; Galambosi, 2012).