Tinzaparin use in pregnancy: an international, retrospective study of the safety and efficacy profile

Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):293-9. doi: 10.1016/j.ejogrb.2011.08.005. Epub 2011 Sep 25.

Abstract

Objectives: This study audited pregnancies where the mother received tinzaparin (at any stage before delivery), with a primary objective of determining the maternal safety of this low molecular weight heparin when administered as treatment and/or prophylaxis; the secondary objective was to audit fetal and neonatal safety in this cohort. Efficacy outcomes were also recorded.

Study design: The audit period was 1996-2009; consecutive, retrospective pregnancy records at participating hospitals were reviewed. For those records documenting tinzaparin use and pregnancy outcome, information was extracted into a standardised case report form; these were reviewed for adverse events, which were submitted for adjudication by independent experts in obstetric medicine and haematology. Endpoints were presented using descriptive statistics for all pregnancies, and by reason for tinzaparin use (treatment of venous thromboembolism [VTE] and prophylaxis).

Results: There were 28 participating hospital centres in eight countries (Belgium, Canada, Denmark, Ireland, Netherlands, Sweden, Spain and the UK). Data were collected from 1267 pregnancies (1120 women; 1303 fetuses); in 254 pregnancies the women received tinzaparin as treatment (median dose 13,000 international units [IU]/day, range 3500-23,100IU/day; median duration 72 days; 94.1% once-daily), and in 1013 pregnancies the women received tinzaparin for prophylaxis (median dose 4500IU/day, range 2500-21,811IU/day, median duration 183 days, 94.6% once-daily). There were 871 (70.2%) vaginal deliveries (78 assisted) and 369 (29.8%) caesarean sections (27 delivery data missing). Overall, 495 (39.3%) women had neuraxial anaesthesia; however, there were no reported associated haematomas. There were no maternal deaths. Of pregnancies with available data (1060), 86.9% had blood loss ≤500mL, 11.0% of >500 to ≤1000mL, 0.9% >1000 to ≤1500mL and 1.1% >1500mL. There were 1245 (95.5%) live births, 15 (1.2%) stillbirths, 40 (3.1%) miscarriages and 3 (0.2%) terminations. Six (0.5%) neonatal deaths occurred (five at <27 weeks, one Ebstein's anomaly). No neonatal haemorrhages occurred. Adjudicated safety outcomes included 125 (9.9%) 'any bleeding' cases considered related to tinzaparin; 16 (1.3%) of these required medical intervention. In the treatment group, five (2%) recurrent VTEs were reported and 10 (1%) occurred in the prophylaxis group.

Conclusions: These data provide reassuring maternal and fetal outcome information in pregnancies exposed to tinzaparin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Canada
  • Cohort Studies
  • Europe
  • Female
  • Fibrinolytic Agents / adverse effects*
  • Fibrinolytic Agents / therapeutic use
  • Heparin, Low-Molecular-Weight / adverse effects*
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Infant Mortality
  • Infant, Newborn
  • Male
  • Medical Audit
  • Middle Aged
  • Postpartum Hemorrhage / chemically induced
  • Postpartum Hemorrhage / therapy
  • Pregnancy
  • Pregnancy Complications, Cardiovascular / drug therapy*
  • Pregnancy Complications, Cardiovascular / prevention & control*
  • Pregnancy Outcome
  • Retrospective Studies
  • Secondary Prevention
  • Tinzaparin
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / prevention & control*
  • Young Adult

Substances

  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Tinzaparin