P268
Use of Enoxaparin and Anti-factor Xa Monitoring in a Renal Obstetric Cohort
Sarween N1, Probert L1, Webster J2, Lester W2, Knox E3 Lipkin G1and Day C1
University Hospital Birmingham NHS Foundation Trust, Department of Renal Medicine 1
Birmingham Women’s NHS Foundation Trust, Department of Haematology2 and Obstetrics3
Introduction: Pregnancy is a major risk factor for venous thromboembolic disease (VTE)
which is compounded by other thrombophilia including heavy proteinuria. Guidelines therefore
recommend prophylactic use of low molecular weight heparin (LMWH) for patients deemed at
high antenatal risk. The Royal College of Obstetricians and Gynaecologists (RCOG)
recommend antenatal thromboprophylaxis with LMWH for pregnant women with nephrotic
syndrome & for some with significant proteinuria continued until 6 weeks post partum.
However, LMWH is cleared by the kidneys and may lead to increased risk of bleeding
complications in those with chronic kidney disease (CKD) because of reduced drug clearance.
Outside of pregnancy dose adjustment is recommended for eGFR < 30ml/min. There are
however no guidelines that exist for dosing or monitoring pregnant women with CKD receiving
LMWH. The VTE protocol, used in our combined Renal-Obstetric antenatal clinic recommends
enoxaparin if urine albumin to creatinine ratio (ACR) exceeds 200 mg/mmol and dose reduction
for those with severe CKD, if serum creatinine is >150µmol/L. The anticoagulant activity of
enoxaparin can be monitored through measurement of factor Xa inhibition which we routinely
employ to guide dose adjustment. The purpose of our study was to review the safety and
efficacy of LMWH dosing and value of plasma anti-factor Xa levels in pregnant women treated
in a tertiary referral antenatal clinic.
Methods: We conducted a retrospective, single centre review of all women attending a tertiary
renal antenatal clinic who received treatment with LMWH during pregnancy over the past 3
years. We reviewed patient demography, primary renal disease, gestation, renal function and
ACR at start of treatment and pregnancy outcome including any complications related to
treatment with LMWH.
Results: 28 pregnancies in 25 women treated with LMWH were identified (median age 30y
(range 17-38)), white Caucasian (63%) South Asian (29%). Sixteen (59%) patients had an
underlying known glomerular pathology, lupus nephritis (5) and IgA nephropathy (3) and six
patients had undiagnosed proteinuria. Urine ACR was >50 mg/mmol (74%) at initiation of
LMWH and over 200 mg/mmol (37%). The creatinine was above 70µmol/L (mild CKD) and
100µmol/L (moderate CKD) in 32% and 21% respectively. LMWH was started at 3.7-34
weeks gestation (mean 11.8). The indication for treatment was heavy proteinuria (68%), 18%
were nephrotic, previous VTE (29%) and antiphospholipid syndrome (18%). Prophylactic
dosing was used in all but 1 case. Anti-Xa levels (measured 3h post dose) averaged 3/patient.
16 women (with completed pregnancies) have had ≥ 2 measurements and of which only 2 had
all results within target range, 69% having experienced at least 1 sub therapeutic level. Antifactor Xa levels were higher (0.24 IU/ml vs 0.17 IU/ml, P<0.02) in women with CKD (antenatal
creatinine >70umol/l) and they were more likely to have had a supratherapeutic measurement
(83% vs 20%, P<0.02) as compared to women with normal renal function. Twenty five
pregnancies had successful deliveries (3 ongoing), 52% were pre-term < 37 weeks and 76% by
caesarean section. There were no cases of VTE whilst on treatment & no significant adverse
reaction to LMWH or intra-partum hemorrhage. Information regarding post partum
hemorrhage was available for 18 deliveries, blood loss being < 500mls in 12 but significant
blood loss in 2 (ventouse 1100 ml and caesarean section 2000ml).
Conclusions: Prophylactic treatment with LMWH in pregnant women at high risk of VTE with
CKD appears to be safe and effective. Measurement of anti-factor Xa activity may be helpful in
guiding dosing in women with abnormal renal function during pregnancy.