On therapeutic LMWH
≥24 h after last dose
Next dose LMWH
≥3 h after removal
If analgesia is required for labour before it is considered safe to administer a regional block, fentanyl patient-controlled analgesia may be used with senior anaesthetic involvement.
Intrapartum Anticoagulation Management in Specific Situations
Women Receiving Prophylactic Low-Dose LMWH for Recurrent Miscarriage or Previous Adverse Pregnancy Outcome
In these circumstances, LMWH can be discontinued at 34–37 weeks unless there are risk factors for VTE, in which case it can be discontinued 12 hours prior to planned induction, CS or at the onset of labour. There is no need to restart LMWH postpartum unless there is a thrombophilia or other identified risk factors for VTE.
Women Receiving Prophylactic Low-Dose LMWH for VTE Prophylaxis Because of Previous VTE or Other Identified Risk Factors for VTE
These women may be advised to discontinue LMWH 12 hours prior to planned induction, CS or at the onset of labour. This ensures that for planned delivery there is at least a 12-hour window to allow siting of regional anaesthesia or analgesia.
There is a possibility that with this strategy, particularly in a multiparous woman in whom the plan is to await the onset of spontaneous labour, that she may request (and be declined) an epidural within 12 hours of her last dose of LMWH. This is also more likely in women receiving high-dose prophylaxis (e.g. enoxaparin 40 mg twice daily). This possibility should be discussed with the individual patient and a risk assessment made of the relative merits of earlier discontinuation of LMWH versus a possible delay in receiving pain relief via an epidural.
If a CS is required less than 12 hours after the last dose of LMWH, this will need to be performed under general anaesthetic. Alternatively, it may be appropriate to request an anti-Xa level and proceed with a regional block if this is very low.
LMWH should be restarted within 4–6 hours postpartum and continued for six weeks in the case of previous VTE, hereditary thrombophilia with a family history, or sickle cell disease.
Women Fully Anticoagulated with LMWH
The main indications for full anticoagulation in pregnancy are:
1. VTE in the current pregnancy; and
2. metal heart valves.
VTE in the Current Pregnancy [4]
The highest risk of further thrombosis or a pulmonary embolus following a deep venous thrombosis is in the first few weeks after the index event. This provides a very strong rationale for delaying delivery if possible in women who develop VTE at or near term. This allows for a longer period of full anticoagulation before the necessary temporary interruption for delivery. These women can be managed in a similar way to women on prophylactic LMWH but with cessation of LMWH 24 hours prior to planned induction, CS or at the onset of labour. For a CS, regional anaesthesia can then be safely employed. For women in labour or undergoing induction of labour, several strategies are possible starting from 24 hours after the last therapeutic dose of LMWH:
1. Withhold heparin until after delivery (facilitating use of regional analgesia if required); not suitable if VTE less than one week before delivery.
2. Give further prophylactic dose of LMWH every 24 hours in labour (considering/offering siting of an epidural prior to each dose).
3. Give doses of subcutaneous prophylactic unfractionated heparin (7500 IU) every 12 hours (allowing siting of an epidural after two hours).
4. Elective placement of an epidural catheter that may be used if required (allowing a further dose of LMWH to be given after three hours).
5. Use intravenous unfractionated heparin (UFH). The dose of intravenous heparin used is designed to provide prophylactic levels (about 1000 units/hour). The infusion is discontinued at onset of the second stage of labour or interrupted 1–2 hours prior to regional anaesthesia or analgesia.
All strategies should include use of grade II elastic compression stockings. Whichever option is employed, the implications should be carefully explained to the woman. Full anticoagulant doses of LMWH should be recommenced after delivery, remembering that the correct therapeutic dose for enoxaparin and dalteparin falls to the normal non-pregnant dose, i.e. 1.5 mg/kg daily. This can be divided into a bd regime if there is concern about giving a large bolus dose. If there is concern about PPH, the dose can be kept at high prophylactic levels until this concern passes. It is important to remember that PPH and blood transfusion are independent risk factors for VTE.
Metal Heart Valves
Women with metal heart valves may be on warfarin or full therapeutic doses of LMWH antenatally to prevent valve thrombosis [6]. Warfarin should be stopped ten days to two weeks prior to delivery to allow clearance of warfarin by the fetus. Anticoagulation should then be continued with full anticoagulant doses of LMWH which does not cross the placenta. When LMWH is used, low-dose aspirin (75 mg daily) should be added as an adjunctive antithrombotic therapy.
Many clinicians prefer to plan delivery in women with mechanical heart valves. The risk of valve thrombosis is high in these women and for those maintained on warfarin antenatally, stopping this at 36 weeks, replacing it with full anti-coagulation doses of heparin, and inducing labour or performing a CS (if obstetrically indicated) at 38 weeks minimizes the time spent off warfarin. In women where the risk of thrombosis is lower (large aortic new-generation valves, e.g. Carbomedics) for whom the decision was taken to convert to LMWH for the entire pregnancy, it would seem reasonable to await spontaneous labour unless there is an obstetric reason for earlier delivery.
LMWH should be stopped as soon as contractions start. If labour is to be induced, LMWH should be stopped 24 hours before induction. Regional analgesia can be administered 24 hours after the last dose of therapeutic LMWH.
As a general rule, some form of anticoagulation should be administered within 24 hours of the last dose of therapeutic LMWH. Thus option (1) above is not appropriate for women with metal valves. Options (2)–(4) may be employed, but some clinicians prefer to use option (5). The latter is labour intensive, requires admission to hospital and careful monitoring of APTT levels which can be very problematic, and often leads to under- or overanticoagulation.
For women with VTE in the index pregnancy or those with mechanical valves, full anticoagulant doses of heparin should be resumed after delivery. This can be with subcutaneous LMWH. Conversion back to warfarin should be delayed for at least 5–7 days to minimize the risk of secondary PPH. It is important to continue LMWH until the INR is ≥2 for VTE or INR ≥2.5 with mechanical valves.
Women Presenting in Labour or Needing Urgent Delivery Fully Anticoagulated on Warfarin or Heparin
In the event of an urgent need to deliver a fully anticoagulated patient, warfarin may be reversed with fresh frozen plasma (FFP) and vitamin K (1 mg intravenously is usually sufficient), and UFH with protamine sulphate. Unfractionated heparin has a short half-life and reversal is not usually required (especially not with doses of 1000 units per hour as suggested above). LMWH is partially reversed with protamine sulphate. However, bleeding complications are uncommon with LMWH. There is a 2% chance of wound haematoma with both LMWH and UFH. If a fully anticoagulated patient requires a CS, this should be performed under general anaesthesia with consideration given to insertion of wound drains and use of staples or interrupted skin sutures.
If vitamin K has been given, anticoagulation with warfarin postpartum becomes very difficult. Both warfarin and LMWH are safe to use in a mother who is or intends to breastfeed.
Thrombocytopenia
The key concerns in labour and delivery in a woman with thrombocytopenia are [7]:
administering a regional anaesthetic;
surgical bleeding;
PPH; and
fetal intracranial haemorrhage in a thrombocytopenic fetus.
Anaesthetists will usually not site a regional anaesthetic if the platelet count is <80 × 109/L due to concerns around epidural haematoma. Surgical incisions can, however, be made safely with counts of >50 × 109/L. The aim of pre-delivery is to keep the platelet count above 50 × 109/L (see Table 22.3).
| Platelet count × 109/L | Action |
|---|---|
| <20 | Treat* |
| >20 | Treat if symptomatic* |
| 30 | Possibly safe for vaginal delivery |
| >50 | Safe for vaginal delivery and caesarean section |
| >80# | Considered safe for regional analgesia |
Delivery is the time of maximum concern for the thrombocytopenic mother. The risk of maternal and fetal haemorrhage is not reduced with CS compared with an uncomplicated vaginal delivery. Caesarean section should therefore only be performed for obstetric reasons. Ventouse delivery should be avoided, but the use of traction forceps should be considered if there is a delay in the second stage.
If the third stage is managed actively using oxytocin, there is seldom excessive bleeding from the placental bed. However, there is a risk of bleeding from surgical incisions, soft tissue injuries and tears. A cord platelet count should be performed.
Imminent Delivery with a Platelet Count <50 × 109/L
Management of a patient with a platelet count of <50 × 109/L who is soon to deliver will depend on the aetiology of the thrombocytopenia. It is important to increase the platelet count above 50 × 109/L to prevent maternal bleeding. Close liaison with the consultant haematologist should occur. If the diagnosis is idiopathic thrombocytopenic purpura (ITP), a condition caused by anti-platelet antibodies, platelet transfusion will only help transiently, as the antibodies will destroy the platelets transfused. Platelets should only be transfused in this instance if delivery is imminent or if an invasive procedure such as central venous line insertion is required. They should be transfused immediately prior to the procedure. If delivery is not imminent, treatment should be with intravenous human IgG (IVIG), which can raise the count within 48–72 hours. Anti-D can be used as an alternative if the woman is Rhesus positive, but may not be available at the high doses required. Steroids take longer to elevate the platelet count.
If the thrombocytopenia is not due to anti-platelet antibodies, then platelets can be transfused to elevate the count. Platelet transfusion will also be beneficial where there are abnormally functioning platelets. In conditions where the patient may require recurrent platelet transfusions in the future, HLA-matched platelets should be ordered if time permits.
Inherited Coagulation Deficiencies
Haemophilia and von Willebrand Disease (VWD)
Haemophilia A and B are sex-linked recessive disorders with a deficiency of coagulation factors VIII (FVIII) and factor IX (FIX) respectively. Heterozygous female carriers usually have FVIII and FIX levels 50% of normal, but are usually asymptomatic. There is a 50% chance that any male offspring will have haemophilia A or B.
Von Willebrand disease is a quantitative or qualitative deficiency of von Willebrand factor (VWF). Deficiency of VWF results in FVIII deficiency and abnormal platelet function. Types 1 and 2 are autosomal dominant and type 3 is autosomal recessive.
Treatment
Maternal FVIII levels and VWF increase with gestation and may be normal by the time of labour and delivery. Maternal FIX levels do not rise significantly in pregnancy. A plan for delivery should be made with the haematologist, obstetrician and anaesthetist before delivery [8,9].
Treatment should be given with haematological advice (see Box 22.2). Recombinant factor VIII or IX may be used as well as Desmopressin (DDAVP). DDAVP is a synthetic analogue of vasopressin which increases the levels of endogenous VWF and FVIII in patients with mild haemophilia A, in carriers of haemophilia A and in most patients with VWD. It increases the level of VWF and FVIII 3–5-fold within half-hour. The increased levels are maintained for 6–8 hours. Close monitoring for water retention should accompany DDAVP use. It should be used only with caution in women who also have pre-eclampsia.
Any clotting factor level of <50 IU/dl prior to insertion of a regional block (which should be performed by a senior anaesthetist) and for all types of delivery.
Type 2 VWD for operative delivery or perineal trauma.
Type 3 VWD for all types of delivery.
Regional analgesia/anaesthesia is generally not recommended for those with type 2 or 3 VWD.
Delivery
Women with hereditary coagulation deficiencies who are pregnant with an affected fetus and women with severe VWD should deliver at a unit where the necessary expertise in the management of these disorders and resources for laboratory testing and clotting factor treatments are readily available. Blood should be grouped and saved.
The male fetus of a haemophilia A or B carrier and the male or female fetus of a woman with VWD types 1 and 2 have a 50% chance of being affected. Vaginal delivery carries a small risk of serious fetal or neonatal bleeding in an affected fetus, which may be reduced, but is not eliminated by CS. After discussion with the couple, if vaginal delivery is chosen with an affected or potentially affected fetus, fetal scalp electrodes, scalp fetal blood sampling, ventouse extraction and rotational forceps delivery should not be performed. Lift-out forceps may be used if required. A prolonged second stage should be avoided. The third stage should be actively managed. Cord blood should be sent for clotting factor assay in all male offspring of haemophilia carriers. VWF is elevated in the neonate and testing should be delayed.
Postnatally
The gestation-related rise in FVIII and VWF reverts postnatally. Prophylactic recombinant clotting factor or DDAVP may be required to keep clotting factor levels >50 IU/dl for 3–5 days following delivery. Tranexamic acid may help control prolonged and/or intermittent secondary PPH. The affected neonate should be given oral vitamin K.
Sickle Cell Disease
Women with sickle cell disease should be delivered in hospitals which have the relevant multidisciplinary team available to manage any complications that may arise from sickle cell disease and from high-risk pregnancies [10]. This will usually be a tertiary unit. Preterm birth is common in those with sickle cell disease. This is due to spontaneous preterm labour as well as iatrogenic due to complications including pre-eclampsia, recurrent crises and placental insufficiency from placental infarcts leading to fetal growth restriction.
Pregnant women with sickle cell disease who have a normally grown fetus should be offered delivery after 38 weeks’ gestation, usually by induction of labour. Vaginal birth after CS can be considered. When aiming for a vaginal delivery, consideration should be given to suitable birthing positions in women who have avascular necrosis of the hips, with or without hip replacement(s).
Operative delivery increases the risk of infection, sickle cell crises, acute chest syndrome (ACS) and thromboembolism in women with sickle cell disease and hence CS should only be performed for obstetric reasons.
There should be close involvement with the haematology consultant. Before a planned delivery in a woman with recurrent crises or ACS, it may be necessary to perform an exchange transfusion, particularly if the percentage of sickle cells is high.
Sickle cell crises can be precipitated by dehydration, infection and the increased catecholamine response to pain, all of which may occur in labour. Women should be kept well hydrated and warm, and receive 2 l/min oxygen via nasal prongs or mask. Regional analgesia is recommended for pain control. Pethidine should be avoided, although other opiates can be used if necessary. Blood should be grouped and saved, but if atypical antibodies are present it is recommended that blood should be cross-matched. Broad-spectrum antibiotics should be administered if there is any suspicion of infection and routinely after operative delivery. The fetus is often growth-restricted and hence continuous fetal monitoring should be performed.
Continuous positive airway pressure (CPAP) may be advocated postnatally to reduce the incidence of ACS, particularly in postoperative patients. Acute chest syndrome is the most common cause of postoperative death among patients with sickle cell disease. Women should use graduated elastic compression stockings and be given prophylactic LMWH for six weeks postnatally to prevent thromboses.
Diabetes
Women with diabetes should be delivered in a consultant-led maternity unit with access to senior medical, obstetric and neonatal staff [11].
Pre-Existing Diabetes
The key concerns in labour and delivery in a diabetic pregnancy are:
timing of delivery to avoid stillbirth and shoulder dystocia;
mode of delivery to avoid shoulder dystocia; and
diabetic control in labour to prevent maternal diabetic ketoacidosis and neonatal hypoglycaemia.
Delivery
Women with diabetes should be advised to give birth in hospitals where advanced neonatal resuscitation skills are available 24 hours per day. Delivery of a woman with pre-existing diabetes by 38 completed weeks is recommended in uncomplicated pregnancies with normal growth to avoid the increased risk of stillbirth, reduce the prevalence of macrosomia and reduce the risk of shoulder dystocia. Vaginal delivery is preferable, hence many diabetic women are induced. Vaginal birth after CS can be offered to diabetics. For women who have diabetes and a diagnosis of fetal macrosomia based on ultrasound, there should be a discussion regarding the merits and risks of vaginal birth, induction of labour and CS. In diabetic pregnancies 80% of cases of shoulder dystocia occur above a birth weight of 4.25 kg.
Diabetic Control in Labour and Delivery
Glucose control throughout active labour and delivery should be maintained between 4–7 mmol/l. Often this is best achieved with a sliding scale of short-acting intravenous insulin and dextrose, as the dietary intake in labour is reduced and metabolism is varied (see Box 22.3). This infusion should be considered from the onset of established labour in women with type 1 diabetes.
Fifty units of short-acting insulin, e.g. actrapid or Humulin S in 50 ml of 0.9% sodium chloride at a rate determined by capillary blood glucose.
Fluid regimen:
5% dextrose + 20–40 mmol of KCl infusion 1 l per eight hours if blood glucose <12 mmol/l.
0.9% sodium chloride + 20–40 mmol of KCl 1 l in eight hours if blood glucose >12 mmol/l, switch to 5% glucose when blood glucose falls to <12 mmol/l.
The sliding scale used will depend on whether they have type 1 or type 2 diabetes and the individual daily insulin requirements. Examples of such scales are shown in Tables 22.4–22.5. The capillary blood glucose (BM) is estimated each hour and the insulin infusion rate adjusted accordingly. The usual insulin dose range is 2–6 units per hour. The aim is to maintain glucose levels of 4–7 mmol/l during labour and delivery, avoiding hypoglycaemia and preventing ketoacidosis. This may be difficult and most centres will aim for 4–8 mmol/l. Separate giving sets should be used for the insulin and dextrose so that in the event of hypoglycaemia, the glucose infusion can be increased and insulin infusion can be stopped. Women with type 1 diabetes are at particular risk of diabetic ketoacidosis which has a high mortality rate. Urinary ketones should be checked each time urine is passed and particularly if the BM is greater than 15.
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