Elsevier

Thrombosis Research

Volume 98, Issue 2, 15 April 2000, Pages 133-138
Thrombosis Research

Regular article
Pharmacokinetic Profile of a Low-Molecular Weight Heparin (Reviparin) in Pregnant Patients: A Prospective Cohort Study*

https://doi.org/10.1016/S0049-3848(99)00228-5Get rights and content

Abstract

Anticoagulant therapy during pregnancy is problematic. Patients are frequently treated with long-term low-molecular weight heparin despite a lack of evidence for its effectiveness, and in the absence of validated dosing recommendations. The objectives of this investigation were to characterize the safety and pharmacokinetic behavior of a low-molecular weight heparin (reviparin) administered throughout pregnancy. Forty-two patients followed in a tertiary-care rheumatology clinic who received prophylactic doses of reviparin (4900 anti-Xa units subcutaneously once daily) were enrolled in this investigation. Anti-Xa heparin levels, weights, and gestational ages of the patients were obtained on up to four occasions distributed throughout their pregnancy. The achieved anti-Xa heparin levels were highly correlated with the patient's weight, irrespective of the gestational age. No toxicity other than injection site hematomas was observed. The achieved intensity of anticoagulation with reviparin varies during pregnancy in direct proportion to the patient's weight. This variability may mandate dose adjustment in response to changes in a patient's weight during pregnancy, particularly if low-molecular weight heparin is administered at therapeutic doses.

Section snippets

Materials and Methods

The T.E.R.M. (Treatment and Evaluation for Recurrent Miscarriage) program is a multidisciplinary clinic for the evaluation and management of women with a history of recurrent fetal loss. As part of an ongoing evaluation of LMWH for the prevention of recurrent fetal loss at this clinic, consecutive patients with a history of unexplained fetal loss were asked to participate in a pilot study examining the use of LMWH in high-risk pregnancies. To be eligible for this evaluation, all patients had

Results

Reviparin was administered at a dose of 4900 units once daily to 42 patients and anti-Xa heparin levels were obtained between 6 and 37 weeks gestation (mean 20.6 weeks). Heparin levels were determined as soon as immediately after subcutaneous administration, or as late as 23 hours, 35 minutes after injection (mean, 9 hours and 14 minutes after injection; median, 8 hours after injection). No patients were lost to follow-up during the course of the investigation.

Anti-Xa heparin levels displayed a

Discussion

The anti-Xa heparin level achieved in pregnant patients receiving a fixed, once-daily subcutaneous dose of reviparin varied inversely with their weight. Thus, the initial degree of anticoagulation is dependent on the patient's baseline weight. The achieved degree of anticoagulation falls throughout pregnancy, as the patient's weight increases. This suggests that dose adjustment, to reflect changes in patient weight, will be required during pregnancy if the therapeutic goal is to maintain a

Acknowledgements

Dr Crowther holds a Research Scholarship from the Medical Research Council of Canada. Dr Ginsberg is a career investigator of the Heart and Stroke Foundation of Canada.

References (25)

  • M.M Koopman et al.

    Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group

    N Engl J Med

    (1996)
  • Low-molecular weight heparin in the treatment of patients with venous thromboembolism

    N Engl J Med

    (1997)
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    *

    The results of this paper were presented at the International Society of Thrombosis and Hemostasis Meeting in Washington D.C. in August of 1999.

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