Transactions of the Twenty-Fourth Annual Meeting of the Society for Maternal-Fetal Medicine
A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation

https://doi.org/10.1016/j.ajog.2004.05.050Get rights and content

Abstract

Objective

The purpose of this study was to determine whether standard therapeutic doses of dalteparin maintain peak therapeutic levels of anticoagulation during pregnancy.

Study design

This was a prospective trial in which 13 pregnancies that required therapeutic anticoagulation were treated with dalteparin 100 U/kg every 12 hours; peak and trough (predose) low molecular weight heparin (anti-Xa activity) levels were monitored every 2 weeks. Dosage adjustments were made to maintain peak anti-Xa activity between 0.5 and 1.0 IU/ml. Bone density and bone turnover markers were measured.

Results

A total of 250 peak and trough low-molecular-weight heparin (LMWH) levels were obtained. Eighty-five percent of pregnancies (11/13) required an upward dosage adjustment. Trough levels were in the therapeutic range only 9% of the time, despite the maintenance of therapeutic peak levels. Bone resorption markers and density were unchanged in singleton pregnancies.

Conclusion

Dalteparin dosing, based on weight alone, every 12 hours is inadequate to maintain most pregnant women in the therapeutic range throughout pregnancy as measured by anti-Xa activity. Trough levels are rarely in the therapeutic range, despite maintenance of therapeutic peak levels. These notable changes in low molecular weight heparin peak may explain reported failures in pregnancy.

Section snippets

Material and methods

Pregnant women diagnosed with an acute deep venous thrombosis (DVT) by duplex ultrasound examination or women who required therapeutic anticoagulation during pregnancy attending the High Risk Obstetric Practices at University of Colorado Health Sciences Center from 2001 through 2003 were study candidates. Informed consent was obtained by the principle investigator, and the study was approved by the Colorado Medical Institutional Review Board. Patients were excluded for pulmonary embolism, renal

Results

A total of 138 peak and 112 trough anti-Xa levels were obtained in 13 pregnancies in 12 women, for a total of 250 LMWH levels. The characteristics of the women who required therapeutic anticoagulation are described in Table I. All pregnancies were singleton, with the exception of a twin pregnancy in patient 5. Dalteparin was continued until near delivery or until pregnancy loss in all patients; the mean duration of dalteparin therapy was 16 weeks. All women had either an acute venous

Comment

This is the first prospective study in which peak (n = 138) and trough (n = 112) LMWH levels (anti-Xa activity) were monitored to determine whether a commonly used LMWH, dalteparin, would achieve peak therapeutic levels of anticoagulation in pregnancy when given every 12 hours at the recommended dosage per kilogram by the manufacturer. Our study demonstrates that in 85% of pregnant women, the dose of 100 U/kg every 12 hours was insufficient to achieve or maintain peak therapeutic levels of

Acknowledgments

We thank Pamela A. Lekahal for her significant contributions in the appropriate monitoring and follow-up of these patients and Kayla Carstens in the Special Endocrinology Laboratory for ensuring that all the N-Telopeptide measurements were collected appropriately and run in a timely fashion.

Cited by (0)

Supported by Pharmacia and Upjohn grant #524E-CVD-0042-0016.

Presented at the Twenty-Fourth Annual Meeting of the Society for Maternal Fetal Medicine, New Orleans, LA, February 2-7, 2004.

Reprint requests: Reprints will not be available from the authors.

View full text