title: Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy.
abstract: Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered direct comparative studies.
authors.affiliation: National Centre for Hereditary Coagulation Disorders, St James's Hospital, Ireland. jodonne@tcd.ie
authors.forename: Fionnuala
authors.initials: F
authors.lastname: Ní Ainle
authors.forename: Audris
authors.initials: A
authors.lastname: Wong
authors.forename: Niamh
authors.initials: N
authors.lastname: Appleby
authors.forename: Brigitte
authors.initials: B
authors.lastname: Byrne
authors.forename: Carmen
authors.initials: C
authors.lastname: Regan
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hassan
authors.forename: Marie
authors.initials: M
authors.lastname: Milner
authors.forename: Ann O
authors.initials: AO
authors.lastname: Sullivan
authors.forename: Barry
authors.initials: B
authors.lastname: White
authors.forename: James
authors.initials: J
authors.lastname: O'Donnell
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006801:Humans; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D011256:Pregnancy Outcome; D018566:Pregnancy, High-Risk; D012189:Retrospective Studies; D000078222:Tinzaparin; D054556:Venous Thromboembolism / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin