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.

Safety of Therapeutic Doses of Tinzaparin During Pregnancy

“…The very low risk of antepartum major bleeding (0%) found in this study is consistent with that previously reported in the literature, including series reporting twice-daily injections of LMWH during pregnancy [8,20,21,22,26,27,28] and with the bleeding rates reported with the use of LMWH in the non-pregnant population [18,29,30]. …”

“…Indeed, except for some recent data from a large multicentre registry [22], only 3 small series reported the use of once-daily therapeutic doses of tinzaparin during 12, 28 and 37 pregnancies respectively [20,21,26]. The large study by Nelson-Piercy et al [22] reported on 1,267 pregnancies treated with tinzaparin at prophylactic (n = 1,013) or therapeutic dosage (n = 254).…”

“…The mean gestational age at tinzaparin initiation was 13 ± 10 weeks (median, 12 weeks [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37]). All women received a single subcutaneous injection of tinzaparin sodium per day, adjusted to their weight at the start of treatment (175 IU/kg).…”

“…During pregnancy, there is limited reported experience to support the use of this drug at therapeutic doses [20,21,22]. The main objective of this study was to retrospectively assess the safety of therapeutic doses of tinzaparin (175 IU/kg/day) administered once daily for the treatment of VTE during pregnancy at 3 tertiary care centres in France.…”

Diagnosis and Management of Cerebral Venous Thrombosis

“…During treatment, no systemic venous thrombosis occurred; however, 1 parietal infarct and 1 postpartum CVT were documented. 242 As in nonpregnant women, fibrinolytic therapy is reserved for patients with deterioration despite systemic anticoagulation, and its use has been reported during pregnancy. 243 …”