Low Molecular Weight Heparin for treatment and prophylaxis of Venous Thromboembolism (VTE) during Pregnancy
Introduction: Pulmonary embolism (PE) and deep vein thrombosis (DVT) are two components of a single condition called venous thromboembolism (VTE). In pregnancy although VTE is rare (1-2 per 1,000 pregnancies), it remains a leading cause of maternal death, as well as a source of maternal morbidity.
Risk factors for VTE can change during pregnancy, delivery and the postnatal period. A VTE can occur any time in all three trimesters of pregnancy, but the highest risk is in the 6 weeks immediately after birth.
Personal history of VTE is the biggest risk factor for pregnancy associated VTE. Other antenatal risk factors include: medical co-morbidities, increased BMI, advanced age, parity, smoking status, assisted conception and varicose veins. Postnatal risk factors also consist of caesarian delivery (with greater risk associated with emergency caesarean delivery), prolonged hospital admission, postpartum haemorrhage and systemic infection.
Failure to recognise and/or treat personal or pregnancy specific risk factors has been identified as a significant contributing factor to maternal mortality and morbidity from VTE in pregnancy. For this reason and due to the increasing prevalence of risk factors in the pregnant and postpartum populations, all pregnant patients should undergo a documented assessment of risk factors for VTE in early pregnancy or prepregnancy. Risk assessment should be repeated on each admission to hospital, upon any change in clinical status and essentially in the postpartum period. Women who are at a high risk for VTE and/or treated for VTE in pregnancy should be managed by a combined haematology and obstetric multidisciplinary service.
The 2013 Irish National Clinical Guideline on VTE thromboprophylaxis in pregnancy issued a rapid risk assessment tool for VTE in pregnancy and this tool or a variation thereof is used in most Irish maternity hospitals and units.
Low Molecular Weight Heparin (LMWH) is the treatment and prophylaxis of choice for VTE during pregnancy as LMWH is a large molecule and does not cross the placenta. Tinzaparin (Innohep®) and enoxaparin (Clexane®) are the LMWHs most frequently used during pregnancy in Ireland.
Direct oral anticoagulant agents (DOACs) are not routinely recommended for use in pregnancy or breastfeeding due to limited human safety data. Warfarin should be avoided during pregnancy as it can cause birth defects e.g. fetal warfarin syndrome, however it may sometimes be used in patients with mechanical heart valves. At daily doses lower than 12 mg, warfarin can be prescribed during breastfeeding due to very low levels in breastmilk.
The dose of LMWH should be rounded up or down to a measurable dose for administration.
Enoxaparin dose calculation:
Antenatal weight 62 kg
Dose = 1 mg/kg every 12 hours = 62 mg (rounded to 60 mg)
Use 60 mg syringe of enoxaparin sodium per 0.6 mL.
Postnatal weight 71 kg
Dose = 1.5 mg/kg every 24 hours = 106.5 mg (rounded to 105 mg)
Use 120 mg enoxaparin sodium in 0.8 mL syringe, discard 0.1 mL and administer 0.7 mL (105 mg)
Enoxaparin pre-filled syringes are not available for all required doses. Table 2 (on page 20) shows the available syringe sizes and the volume to be administered to obtain the required dose.
Tinzaparin dose calculation:
Weight (antenatal or postnatal)
78 kg Dose = 78 x 175 IU = 13,650 IU (rounded to 14,000 IU)
Use tinzaparin 14,000 in 0.7 mL prefilled syringe.
Tinzaparin pre-filled syringes are not available for all required doses. Table 3 below shows the available syringe sizes and the volume to be administered to obtain the required dose.
It is important that the patient receives the same strength prefilled syringe on each occasion to avoid the chance of a medication or administration error from occurring.
Many maternity hospitals follow the doses suggested above, but in some hospitals the weight bands are further divided so prescriptions for tinzaparin 6000 IU and 8000 IU once daily are common.
Commencement and prophylaxis duration with LMWH can vary depending on individual VTE risk assessment, if LMWH is required during pregnancy it should be continued for up to 6 weeks postnatally.
Enoxaparin (Clexane®) syringes are available in the strengths stated in the table above. However, tinzaparin (Innohep®) syringes are not available in all the doses stated above so the patient will have to be shown how to expel some of the injection from a syringe of a strength closest to their required dose as per Table 3. It is important that the patient receives the same strength prefilled syringe on each occasion to avoid the chance of a medication or administration error from occurring
Contraindications to LMWH use in pregnancy and the puerperium:
Contraindications to LMWH use include known bleeding disorders (e.g. haemophilia, von Willebrand’s disease), thrombocytopenia, acute stroke, active antenatal or postpartum bleeding and those with an increased risk of major haemorrhage (e.g. placenta praevia). As well as uncontrolled hypertension, severe liver or renal disease and recent surgery to the eye or nervous system. Women with a previous or current allergic reaction to LMWH should always be offered an alternative form of prophylaxis. It is recommended that any woman with a contraindication to LMWH should be provided with appropriately sized anti-embolism stockings (AES) with a calf pressure of 1415 mmHg.
LMWH should be avoided if a lumbar puncture, epidural or spinal anaesthesia is expected within the following 12 to 24 hours, or if such regional techniques have taken place within the previous 4 hours. Pregnant patients receiving antenatal LMWH should be educated on the symptoms of labour and instructed not to inject any further LMWH once labour symptoms or vaginal bleeding are observed.