An audit of therapeutic anticoagulation with Anti-Xa monitoring during pregnancy

ABSTRACT

The risk of venous thromboembolism (VTE) increases by 10% in pregnancy to around 1/1000 and is a leading cause of death in pregnant women. Low molecular weight heparins (LMWHs) are the anticoagulant of choice for treatment of acute VTE during pregnancy. The initial dose of LMWH is weight based but currently there is lack of evidence supporting routine Anti-Xa monitoring during pregnancy and LMWH dose adjustments based on Anti-Xa levels. We conducted a retrospective audit of pregnant patients receiving therapeutic dose LMWH between October 2020 and October 2021 in a tertiary referral centre. The aim of this audit was to review LMWH dosages required in pregnancy to achieve peak Anti-Xa levels relative to weight-based and report maternal thrombotic or bleeding outcomes based on dose adjustments. A total of 21 pregnant patients were included who required therapeutic LMWH (Tinzaparin) during pregnancy. Of these, 10 (48%) had an acute VTE in the index pregnancy;one (4%) had recurrence of DVT despite weight adjusted LMWH. Ten (48%) were on long-term anticoagulation for a prior VTE including two with antithrombin deficiency and one with JAK 2 positive myeloproliferative disorder. They were all changed to LMWH during pregnancy. The site of acute VTE in index pregnancy (11) included five (45%) deep vein thrombosis (DVT), three (28%) pulmonary emboli (PE), two (18%) had thromboses at an unusual site, and one patient (9%) had a superficial thrombophlebitis with gestational age range 7-40 weeks. Majority of pregnant patients (18/21;86%) had at least one peak Anti-Xa measured, and 12 (67%) patients had dose of LMWH increased at least once to achieve a target peak Anti-Xa level of 0.5-0.7 IU/ml. Five required two dose adjustments, and one required three dose adjustments. Nineteen patients have delivered and two have ongoing pregnancy. Twelve patients had spontaneous vaginal delivery, three assisted vaginal delivery and four had caesarean section for obstetric reasons. No patients had a recurrent thrombosis while on therapeutic dose LMWH and with dose adjustments as per peak anti-Xa level. One patient who presented with an acute DVT at 40 weeks of gestational age (GA) was managed with twice daily therapeutic dose Tinzaparin and insertion of an inferior vena cava (IVC) filter for anticoagulation interruption around delivery. The last dose Tinzaparin was 12 h prior to emergency Caesarean Section. She had postpartum haemorrhage with an estimated blood loss of 1800 ml but did not require blood product support and there was no evidence of progression of her symptoms of VTE or bleeding postoperatively when anticoagulation was resumed. Of note, six patients (29%) had a BMI >30 with five (83%) needing at least one adjustment of LMWH dose based on Anti-Xa levels and two (33%) needing > 2 dose increments with LMWH based on Anti-Xa monitoring. One patient had recurrence of PE on weight based LMWH dose with no recurrence of symptoms when the LMWH dose was adjusted to peak Anti-Xa level. None of the patients developed SARS-CoV-2 infection in the reported cohort. Fourteen (67%) pf pregnant had received their COVID-19 vaccination during this period . None of the thrombotic episodes were associated with COVID-19 vaccination. Although this audit study has limitations due to small patient numbers there was no evidence of increase in bleeding or thrombotic risk with ongoing anticoagulation with Anti-Xa monitoring during pregnancy..