title: Monitoring of anti-Xa in pregnant patients with mechanical prosthetic valves receiving low-molecular-weight heparin: peak or trough levels?
abstract: OBJECTIVE
  We hypothesized that the guideline-recommended peak anti-Xa levels for pregnant women with mechanical prosthetic heart valves (MPHVs) receiving adjusted dose low-molecular-weight heparin (LMWH) are associated with subtherapeutic trough levels and consequently with an inadequate level of anticoagulation.
  
  
  BACKGROUND
  Low-molecular-weight heparin is often used for anticoagulation in pregnant women including those with MPHV. American College of Cardiology/American Heart Association guidelines recommend monitoring of plasma anti-Xa factor peak levels and adjustment of the dose to achieve peak levels of 0.7 to 1.2 U/mL. In spite of these recommendations, cases of valve thrombosis during pregnancy continue to occur.
  
  
  RESULTS
  We studied 30 pregnant patients receiving anticoagulation for various indications with adjusted dose LMWH given subcutaneously twice a day which had both trough and peak anti-Xa levels throughout pregnancy for a total of 187 paired determinations. The recommended peak anti-Xa levels (0.7-1.2 U/mL) were obtained in 123 (66%) of the measurements but in 80% of them, the trough levels were found to be subtherapeutic (<0.6 U/mL). Subtherapeutic trough levels were found in 8 (73%) of the 11 measurements with peak levels of 0.7 to 0.79 U/mL, 17 (74%) of the 23 of 0.8 to 0.89 U/mL, 21 (72%) of the 29 of 0.9 to 0.99 U/mL, and 28 (44%) of the 63 of 1.0 to 1.2 U/mL. There were 42 measurements with peak anti-Xa levels >1.2 U/mL and even in these cases, 13 (31%) of the trough levels were found to be subtherapeutic.
  
  
  CONCLUSIONS
  Anticoagulation with adjusted dose LMWH aimed to achieve guideline-recommended peak levels of anti-Xa for patients with MPHVs is commonly associated with subtherapeutic trough levels. Routine measurement of trough anti-Xa levels is therefore advisable in women with MPHV treated with LMWH during pregnancy to assure adequate level of anticoagulation.
authors.affiliation: Heart Institute, Kaplan Medical Center, Affiliated to the Hebrew University and Hadassah Medical School, Jerusalem, Israel.
authors.forename: Sorel
authors.initials: S
authors.lastname: Goland
authors.affiliation: Heart Institute, Kaplan Medical Center, Affiliated to the Hebrew University and Hadassah Medical School, Jerusalem, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Schwartzenberg
authors.affiliation: Department of Medicine, Division of Cardiovascular Disease, University of Southern California, Los Angeles, CA, USA Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Fan
authors.affiliation: Heart Institute, Kaplan Medical Center, Affiliated to the Hebrew University and Hadassah Medical School, Jerusalem, Israel.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kozak
authors.affiliation: Department of Medicine, Division of Cardiovascular Disease, University of Southern California, Los Angeles, CA, USA Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Nudrat
authors.initials: N
authors.lastname: Khatri
authors.affiliation: Department of Medicine, Division of Cardiovascular Disease, University of Southern California, Los Angeles, CA, USA Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA elkayam@usc.edu.
authors.forename: Uri
authors.initials: U
authors.lastname: Elkayam
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D015951:Factor Xa / Q000032:analysis / Q000187:drug effects*; D005260:Female; D017408:Guidelines as Topic; D006350:Heart Valve Prosthesis; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D015141:Los Angeles; D011247:Pregnancy; D012189:Retrospective Studies; D012955:Societies, Medical
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D015951:Factor Xa
keywords: anticoagulation; low-molecular-weight heparin; mechanical prosthetic heart valves; pregnancy