A case series of LMWH use in pregnancy: should trough anti-Xa levels guide dosing?

Thromb Res. 2014 Dec;134(6):1234-40. doi: 10.1016/j.thromres.2014.09.033. Epub 2014 Oct 2.

Abstract

Introduction: Pregnancy is a thrombogenic state, increasing the risk for venous thromboembolism (VTE), and the risk of valve thrombosis amongst women with mechanical heart valves (MHV). While low molecular weight heparins (LMWH) are generally dosed based on weight (i.e., enoxaparin 1 mg/kg every 12 hours), data in pregnant women have shown that weight-based dosing does not consistently achieve target anti-Xa levels. In women with MHV, our practice includes titrating LMWH doses to target both trough and peak anti-Xa levels, while for those with VTE peak anti-Xa levels guide dosing.

Materials/methods: This retrospective case series included pregnant women requiring LMWH treatment doses with at least 3 peak (+/-trough) anti-Xa levels. Our primary objective was to describe the actual LMWH dose required to achieve targeted anti-Xa levels relative to weight-based dosing in patients with MHV. Secondarily, we compared the same for VTE patients; compared actual dosing between those with MHV and VTE; and examined maternal and fetal outcomes.

Results/conclusion: Women with MHV (N=4) required greater than weight-based dosing of enoxaparin (1.35 mg/kg Q12H) to achieve targeted anti-Xa levels. Importantly, achieving target peak anti-Xa levels did not always ensure maintenance of minimum trough levels. VTE patients (N=12) did not require more enoxaparin (0.96 mg/kg Q12H) than weight based dosing. MHV patients received more enoxaparin compared to VTE patients (P<0.001). No bleeding or clotting complications were associated with LMWH administration. In pregnant women with MHV at high risk of thromboembolism, LMWH dosing guided by trough and peak anti-Xa levels should be considered.

Keywords: Anti-Xa level; Low molecular weight heparin; Mechanical prosthetic valve; Pregnancy; Thrombosis; Venous thromboembolism.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Anticoagulants / administration & dosage
  • Biomarkers / blood
  • Dose-Response Relationship, Drug
  • Factor Xa Inhibitors / blood*
  • Female
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Humans
  • Middle Aged
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / blood*
  • Pregnancy Complications, Cardiovascular / diagnosis
  • Pregnancy Complications, Cardiovascular / drug therapy*
  • Pregnancy Outcome
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity
  • Treatment Outcome
  • Venous Thromboembolism / blood*
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / drug therapy*
  • Young Adult

Substances

  • Anticoagulants
  • Biomarkers
  • Factor Xa Inhibitors
  • Heparin, Low-Molecular-Weight