There is a tenfold increase in thrombotic risk throughout pregnancy and the puerperium.^177,178 The same factors that increase thrombotic risk in non-pregnant patients e.g. obesity, immobility, dehydration, long-distance air travel (see Table 1) also increase the risk of thrombosis associated with pregnancy. During pregnancy additional risk factors such as pre-eclampsia and delivery, particularly operative delivery, must be considered.¹⁷⁹

LMWH is preferred to UFH as it is safer in pregnancy^{180,181,182,183} and is also preferable to warfarin during pregnancy (because of the fetal toxicity of oral anticoagulants).

Warfarin and other coumarins should be avoided if possible during pregnancy, at least between six and 12 weeks gestation and after 36 weeks' gestation.

LMWH is preferred to UFH in pregnancy, as there is more safety data.

All pregnant women should be regularly assessed for VTE risk factors.

9.1 Antenatal thrombosis risk assessment

Women attending for their first antenatal visit should be asked specifically about their personal and family history of VTE and whether any diagnosis was objectively confirmed. If this information is not available, investigate the history of anticoagulant treatment. Where prolonged anticoagulant therapy has been prescribed, in keeping with the management of VTE, it is prudent to assume that this has been a definite event. Patients with thrombophilias appear to be at particular risk of VTE in pregnancy.^184,185,186

All pregnant women with a personal history of VTE, or a family history of VTE in first or second degree relatives, should be offered screening for thrombophilias.

There is accumulating evidence linking congenital thrombophilia to other pregnancy complications, including miscarriage, pre-eclampsia, intrauterine growth restriction and fetal death.¹⁷⁷

9.2 Previous VTE and no identifiable thrombophilias

Where a patient has had a single previous VTE event associated with a temporary risk factor which is no longer present, antenatal anticoagulation is controversial because of the low risks of recurrence and the potential hazards of heparin.¹⁸⁷ Where the previous VTE event was oestrogen-related (e.g. COC use or pregnancy), there is a stronger case for LMWH prophylaxis throughout the pregnancy. The use of LMWH reduces these hazards.¹⁷⁸ Each case should therefore be judged on an individual basis taking into account any additional risk factors, and the patient counselled regarding the potential risks and benefits of antenatal pharmacological thromboprophylaxis. As events can occur early in pregnancy, it is important to assess risk at this time and start thromboprophylaxis if significant risk factors (such as hyperemesis with associated immobility) are present.

Management options should be discussed with each patient.

In all women with VTE events during previous pregnancy or COC use, antenatal thromboprophylaxis should be started as early as possible in pregnancy.

In all women with previous idiopathic VTE, antenatal prophylaxis should be started as early as possible in pregnancy.

Women in whom a previous VTE occurred in association with other temporary risk factors, which are no longer present (e.g. surgery or trauma), and who have no identifiable thrombophilia or current risk factors other than pregnancy, do not routinely require antenatal LMWH prophylaxis, but should be considered for GECS.

Where antenatal thromboprophylaxis is appropriate, it should be: subcutaneous LMWH (e.g. 40mg enoxaparin daily or 5,000 IU dalteparin daily). The platelet count should be checked before and one week after the introduction of LMWH at low body weight, e.g. <50kg, lower doses of LMWH may be required (e.g.20mg enoxaparin daily or 2500 IU dalteparin daily) in obese patients, (e.g. BMI >30 in early pregnancy), higher doses of LMWH may be required GECS may be combined with LMWH. Clinical surveillance for evidence of VTE should also be considered.

All women with a past history of VTE should receive thromboprophylaxis postpartum (see section 9.5).

9.3 Long term anticoagulants or known heritable thrombophilia

Women on long term anticoagulant drugs or with a known heritable thrombophilic defect usually merit referral to a unit experienced in management of pregnancy in thrombophilic women.⁶¹ The risk of VTE associated with thrombophilic defects varies considerably. Patients should be stratified according to the level of risk associated with their thrombophilia.⁶¹ All patients with heritable thrombophilia should be considered for GECS during pregnancy and for six weeks postpartum (see section 9.5).

9.3.1 HIGH RISK OF CLINICAL VTE (>1:40)

• women on long term anticoagulant thromboprophylaxis for VTE
• women who have antithrombin deficiency (whether or not they have had a previous
  symptomatic thrombosis)

These women should be considered at very high risk of antenatal VTE and must be considered for anticoagulant prophylaxis throughout pregnancy. They should be advised of the need to switch from warfarin to LMWH (or to start LMWH) as soon as pregnancy is confirmed. The dose of heparin given should be closer to that used for the treatment of VTE rather than that used for prophylaxis. ⁶¹

In pregnant women at high risk of VTE, prophylaxis should be subcutaneous LMWH, (e.g. enoxaparin 0.5-1mg/kg 12 hourly or dalteparin 50-100 IU/kg 12 hourly) , based on the early pregnancy weight. The platelet count should be checked before and one week after the introduction of LMWH.

Where a LMWH is used, 12 hourly injections may be preferable to once daily injections in view of the increased clearance of LMWH in pregnancy. Women who are receiving long term anticoagulant thromboprophylaxis because of a prosthetic heart valve also require intensive anticoagulation in pregnancy. Such women should be referred to a specialist unit with the experience of management of these problems.

9.3.2 MODERATELY INCREASED RISK OF CLINICAL VTE (1:40 -1:200)

• women with a previous thromboembolic event who have an underlying thrombophilia and who do not belong to the previous high risk category
• women with no personal history of VTE but who have been found (e.g. because of a family history) to be protein C deficient, to have combinations of defects, or to be homozygous for a defect

LMWH prophylaxis should be started in these women as soon as the pregnancy is confirmed.⁶¹

In pregnant women at moderately increased risk of VTE, prophylaxis can be given as LMWH (e.g. enoxaparin 40mg daily or dalteparin 5,000 IU daily). The platelet count should be checked before and one week after the introduction of LMWH.

9.3.3 SLIGHTLY INCREASED RISK OF CLINICAL VTE (1:200 -1:400)

• women with no personal history of venous thrombosis but who have had a defect identified, e.g. because of a family history, and who do not belong to the categories described in 9.3.1 or 9.3.2.

These women do not usually require routine anticoagulant thromboprophylaxis antenatally but should be offered anticoagulant prophylaxis following delivery. The risk of thrombosis should be discussed with the patient antenatally, and GECS considered (see section 9.2). If LMWH thromboprophylaxis is requested, the patient should be treated with LMWH in prophylactic doses (as in section 9.3.2).⁶¹

9.4 Antiphospholipid syndrome

Women with antiphospholipid syndrome (lupus anticoagulants or anticardiolipin antibodies) and recurrent miscarriage should receive thromboprophylaxis with LMWH and low-dose aspirin from the point of diagnosis of pregnancy.^187,188,189 Although such therapy is aimed at preventing pregnancy loss, which is related to placental thrombosis, these women are likely to be at risk of other thromboembolic events and pregnancy complications. Similar prophylaxis should be given to women with antiphospholipid syndrome and a previous thrombotic event.

Women with antiphospholipid syndrome and no previous thrombotic event or recurrent miscarriage should be considered for low dose aspirin (75 mg/day), to reduce the risk of pregnancy complications and postpartum heparin thromboprophylaxis.¹⁷⁸

Women with antiphospholipid syndrome and recurrent miscarriage should receive thromboprophylaxis from the diagnosis of pregnancy with LMWH (e.g. enoxaparin 40 mg daily or dalteparin 5,000 IU daily) and low dose aspirin (75 mg/day).

Women with antiphospholipid syndrome who have already had a thrombotic event should receive low dose aspirin (75 mg/day) and LMWH (e.g. enoxaparin 40mg daily or dalteparin 5,000 IU daily) from the diagnosis of pregnancy.

Other women with antiphospholipid syndrome should receive low dose aspirin (75 mg/day) antenatally to reduce the risk of pregnancy complications, and postpartum heparin prophylaxis (see section 9.5).

9.5 Delivery and the puerperium

9.5.1 MANAGEMENT OF DELIVERY

Patients on LMWH antenatally and who wish epidural anaesthesia in labour, or epidural or spinal anaesthesia for caesarean section, should stop pharmacological prophylaxis when labour starts. In general terms, an epidural or spinal block should not be given for 10-12 hours after LMWH administration (see section 7). However, the risk benefit ratio must be taken into account in the decision regarding timing of epidural or spinal anaesthesia. LMWH should not be given within two hours of epidural or spinal anaesthesia or of catheter removal.

In pregnant women who have requested epidural anaesthesia during labour, stop the administration of LMWH when labour starts.

LMWH can be administered or readministered three hours after atraumatic epidural or spinal anaesthesia, or removal of an epidural catheter.

Patients should be warned to discontinue self-injections of LMWH as soon as they believe themselves to be in labour, and not restart until evaluation in hospital.

9.5.2 MANAGEMENT OF THE PUERPERIUM

In addition to previous VTE and thrombophilias, other risk factors that merit consideration of postpartum prophylaxis include:

• age >35 years
• caesarean section (particularly if carried out as an emergency procedure during labour)
• operative vaginal delivery
• obesity (BMI >30 kg/m²) either pre-pregnancy or in early pregnancy
• parity >=4
• labour >12 hours
• gross varicose veins
• pre-eclampsia
• lower limb paralysis
• immobilisation (>4 days bed rest)
• current infection
• extended major pelvic or abdominal surgery
• major current medical conditions.

Postpartum thromboprophylaxis is recommended in women with: previous VTE (or family history) known thrombophilias other thrombotic risk factors.

Postpartum, the first dose of subcutaneous LMWH (enoxaparin 40mg daily or dalteparin 5,000 u daily) should be given 3-6 hours after delivery.

Postpartum anticoagulation should be continued for a minimum of six weeks in patients with previous VTE or thrombophilias. In other patients, prophylaxis should continue until discharge from hospital; review need for prophylaxis if hospital stay continues beyond five days.

Where the patient does not wish to continue self-injecting, LMWH can be replaced by warfarin starting on the first or second postpartum day. The LMWH can be withdrawn when the INR has been within the target range (usually 2.0 - 3.0) for two consecutive days.

There is no contraindication to breast feeding when the mother is being treated with LMWH, warfarin or other coumarins.

GECS can be added to LMWH in high risk patients and should be used where LMWH is contraindicated.

9.6 Heparin contraindications in pregnancy and puerperium

9.6.1 SKIN REACTIONS

Where LMWH is contraindicated because of skin reactions, consider changing:

• to another LMWH
• to danaparoid if cross-reactivity is excluded
• to low dose aspirin plus GECS.

9.6.2 HEPARIN ALLERGY

In patients with heparin allergy warfarin may be used during pregnancy. However, it must be replaced with LMWH at least four weeks ahead of the expected delivery date. If possible the gestation period 6-12 weeks and post 36 weeks should also be avoided.

9.6.3 HEPARIN ASSOCIATED THROMBOCYTOPENIA

A LMWH or danaparoid may be considered in patients who have heparin associated thrombocytopenia if cross-reactivity has been excluded. Warfarin may be considered in those at high thrombotic risk. Postpartum, warfarin or recombinant hirudin may be considered.

9.6.4 HAEMORRHAGE

Patients with antepartum or postpartum haemorrhage may be at considerable risk of deep venous thrombosis. Clearly while there is a coagulation defect, it would be inappropriate to prescribe UFH or LMWH. These patients should be treated with GECS. Pharmacological thromboprophylaxis can be employed once any coagulation defect has subsided and the haemorrhagic complication has resolved.

Where anticoagulants are contraindicated, GECS should be worn for at least six weeks following delivery. This may be combined with low dose aspirin (75 mg/day).