Clinical Outcomes with the LMWH, Tinzaparin (Innohep®) in Pregnancy. An International Retrospective Audit..

Abstract 487

Low molecular weight heparins (LMWH) have become the parenteral anticoagulant of choice in pregnancy in most current guidelines¹. Several small series of clinical experiences with the LMWH, tinzaparin (Innohep®) in pregnancy have been published and there is data on its pharmacokinetics in pregnancy², but to date there have been no large audits of its efficacy and safety in pregnancy. The aim of this project was to gather this data retrospectively by reviewing maternal and fetal outcomes in consecutive pregnancies in which the mother was treated with tinzaparin, in 8 countries (UK, Ireland, Denmark, Sweden, Spain, Canada, Holland and Belgium).

Using a standard Case Report Form, the hospital staff were asked to start with the most recent pregnancy with an outcome (birth, miscarriage, still birth) in which the mother had any exposure to tinzaparin whilst pregnant and then to work backwards recording consecutive relevant pregnancies (not including the use of tinzaparin solely for prophylaxis at Caesarian section). The data below is provisional, but unlikely to change substantially.

Data were gathered from 1270 pregnancies with a total of 1298 fetuses. The mean prophylactic dose was 6,469 IU (median = 4,500 IU, SD 3,618 IU) daily and the mean treatment dose was 12,761 IU (median = 12,871 IU, SD 3,915 IU) daily. From 1180 of the total population, the mean duration of treatment was 150 days (median = 171 SD = 76). There were 797 (62.8%) vaginal deliveries with 368 (29.0%) caesarian sections, 49 (3.9%) involved ventouse/vacuum and 29 (2.3%) with forceps assistance (data missing for 27(2.1%)). Of the births, 47.5% were induced and 45.7% were spontaneous (data missing for 6.8%). Epidural/spinal anesthesia was administered in 39.1% with no epidural haematoma. Blood loss at delivery was considered normal in 1020 (80.3%) of cases, abnormal in 40 (3.1%) and this data was missing in 210 (16.5%).

In total there were 39 miscarriages and 1,259 births, of which 14 (1.1%) were still births and 1245 (98.9%) live births. There were no maternal deaths, no neonatal hemorrhages and 6 (0.5%) neonatal deaths. Of the neonatal deaths, 4 occurred in babies born at 24 weeks of gestation or earlier, 1 at 27 weeks gestation and the remaining case had Ebstein's anomaly. Congenital abnormalities were reported in 26 (2.1%) cases. In addition, a further infant (reported as a neonatal death) died 7 weeks after birth due to respiratory distress. Although these were pregnancies with significantly higher risks of maternal and foetal morbidity and mortality, the rate of neonatal deaths in this audit (0.5%) is close to the reported figure (0.34%) for all pregnancies in 2006 for the UK³. Likewise the stillbirth rate in this audit was 1.1% against a reported figure of 0.53% for all pregnancies in the UK in 2006³.

Venous Thrombo Embolism (VTE) treatment doses of tinzaparin were administered in 19.8% and prophylactic doses in 80.2%. Results on (re)occurrence of VTE, major bleed, heparin induced thrombocytopenia and osteoporotic fracture are currently being analysed.

These preliminary results provide reassuring maternal and fetal outcome information in pregnancies exposed to tinzaparin. This audit will add further to the knowledge of the safety and efficacy of tinzaparin in pregnancy, as used by clinicians in non clinical trial practice.

Marik P and Plante L.A. Venous Thromboembolic Disease and pregnancy.N. Engl J Med, 2008;359:2025-33.

Smith M. et al. Tinzaparin Sodium for thrombosis treatment and prevention during pregnancy. AJOG, 2004; 190: 495-501

Perinatal Mortality 2006, England, Wales and N.Ireland, CEMACH Publication 2008