Venous thromboembolism in pregnancy

• Overall incidence is low at approximately 2 per 1000 pregnancies (0.2%)
• Risk doubles after conception and rises to 8 to 10 times baseline at term and postpartum
• Thrombosis and thromboembolism is the leading direct cause of maternal death in the UK
• MBRRACE 2021-2023:
• Responsible for 16% of maternal deaths
• Mortality 2.1 per 100,000
• Rate has nearly doubled since the 2009 - 2011 report
• Black women died of VTE at more than twice the rate of white women

• One third to one half of events occur postpartum, mostly in the first 6 weeks; the risk per day is highest in the early postpartum period
• Approximately half of antenatal events occur in the first or second trimester
• A quarter of VTE deaths in recent MBRRACE reports occurred in the first trimester: this is the rationale for early risk assessment before booking

• Rising maternal age, obesity and caesarean section rates
• More women with pre-existing medical conditions

• Hormonally-induced dilatation of capacitance veins reduces linear flow velocity in the lower limb veins despite increased blood volume
• Compression of the IVC and iliac veins by the gravid uterus
• Relative immobility
• Approximately 90% of DVTs in pregnancy are left sided: the left iliac vein is compressed where the right iliac artery crosses it
• Thrombi tend to be proximal (iliofemoral) rather than distal calf vein thrombi as in non-pregnant patients

• Placental separation at delivery initiates and accelerates the clotting cascade
• Amplified by instrumental or caesarean delivery

• ↑ clotting factors I (fibrinogen), V, VII, VIII, IX, X, XII and von Willebrand factor; ↑ thrombin generation
• ↓ natural anticoagulants: protein S falls and there is acquired resistance to activated protein C
• ↑ platelet aggregation after the first trimester; platelet count is unchanged or falls
• Fibrinolytic activity falls in the 48 h after delivery, stabilising clot in the early postpartum period
• The hypercoagulable state takes several weeks to resolve after delivery

• In decreasing order of risk: antithrombin deficiency, factor V Leiden, protein C deficiency, protein S deficiency
• High risk thrombophilia: antithrombin, protein C or S deficiency, or homozygous/compound low risk thrombophilias
• Low risk thrombophilia: heterozygous factor V Leiden or prothrombin G20210A
• Risk increases markedly when combined with a family history of VTE

• Obesity is a consistent risk factor and a recurrent feature in maternal deaths from PE
• Compared with vaginal delivery, risk is roughly doubled with elective and quadrupled with emergency caesarean section

• Assess at the earliest opportunity (ideally pre-conception for high risk women), at booking, and reassess at every admission or change in clinical condition, and on delivery suite
• Risk factors are often unrecognised or untreated, leading to preventable deaths
• The RCOG Green-top Guideline 37a provides a scoring tool for the antenatal and postnatal periods

• Aims to reduce thrombotic events in early pregnancy by risk assessing all pregnant women before antenatal booking and providing rapid access to thromboprophylaxis
• It complements, rather than replaces, the RCOG approach from booking onwards
• Full implementation by NHS trusts and ICBs is expected by March 2027

• A national self-assessment VTE questionnaire (developed with Thrombosis UK) is offered at the first NHS care contact with a positive pregnancy test: e.g. maternity self-referral, GP, ED, early pregnancy unit, fertility clinic, abortion services
• High risk women should be offered LMWH and receive it within 72 hours
• A 4-week prescription is issued, with a follow-up consultation in secondary care within 4 weeks to re-evaluate risk
• ICBs must have prescribing arrangements in place before booking, e.g. primary care prescribing to a community pharmacy

• No routine viability scan is needed before prescribing, unless there is ongoing bleeding or suspected ectopic pregnancy
• After miscarriage or abortion: LMWH for 1 week (restart 6 h after surgical abortion, or after expulsion for medical abortion)
• Not aimed at women on long term anticoagulation: they need an urgent medication review by their usual team
• A maternity exemption (FW8) certificate is issued so the prescription is free of charge

• Mobilisation and avoidance of dehydration for all women

• Graduated compression stockings or intermittent pneumatic compression
• Used in hospitalised women when LMWH is contraindicated, alongside LMWH in some high risk inpatients, and for long distance travel >4 h

• Peripheral arterial disease or bypass grafting
• Peripheral neuropathy or other causes of sensory impairment
• Fragile skin, dermatitis, recent skin graft
• Severe leg oedema or cardiac failure
• Leg deformity or unusual leg size preventing correct fit
• Known allergy to the material

• LMWH is the agent of choice for both prophylaxis and treatment
• Dosed on booking (or most recent) weight; no routine monitoring required
• Reduce dose if creatinine clearance <30 ml/min (enoxaparin, dalteparin) or <20 ml/min (tinzaparin)
• Heparins do not cross the placenta and are safe in breastfeeding

RCOG prophylactic once daily doses; * may be given in two divided doses

• Warfarin: crosses the placenta; embryopathy in early pregnancy, fetal bleeding (including intracranial haemorrhage) later on. Reserved for very high risk women e.g. mechanical heart valves after specialist discussion. Safe in breastfeeding and may be started postnatally
• DOACs (dabigatran, rivaroxaban, apixaban): cross the placenta and lack safety data; may be used postnatally but not if breastfeeding
• Low dose aspirin is not recommended for VTE prophylaxis

• Danaparoid (does not cross the placenta)
• Fondaparinux: longer half-life than LMWH, which matters when planning delivery and neuraxial blockade

• Symptoms and signs are non-specific and mimic normal pregnancy (leg swelling, cramps, breathlessness)
• DVT: unilateral (usually left) leg pain and swelling; may present with lower abdominal, buttock or back pain if iliac
• PE: dyspnoea, pleuritic chest pain, palpitations, cough, syncope, cyanosis, through to shock or cardiac arrest
• Clinical assessment alone is not sufficient: objective imaging is required
• Wells and Geneva scores are not validated in pregnancy

• If VTE is suspected, start treatment dose LMWH before investigations unless delivery is imminent or there is a contraindication; continue until the diagnosis is excluded
• Discuss with a senior clinician
• Baseline bloods before anticoagulation: FBC, coagulation screen, U&E and LFTs
• Thrombophilia screening is not indicated acutely; results are altered by pregnancy and acute thrombosis and do not change management

• D-dimer is not recommended: it rises with advancing gestation
• Suspected DVT: compression duplex ultrasound; if negative but suspicion remains, repeat or consider alternative imaging (lower sensitivity for iliac thrombus)
• Suspected PE: ECG and chest X-ray first
• If there are also leg signs, perform compression duplex first; a confirmed DVT removes the need for further imaging
• If no leg signs: V/Q scan or CTPA depending on local availability and preference
• An abnormal chest X-ray favours CTPA
• If suspicion persists despite normal imaging, repeat or use alternative imaging

Fetal radiation dose from either test is well below the 50 mGy threshold for adverse effects

• DVT: cellulitis, superficial thrombophlebitis, Baker's cyst, haematoma, muscle tear, lymphoedema
• PE: peripartum cardiomyopathy, heart failure, pneumonia, pneumothorax, aortic dissection, amniotic fluid embolism

• Treatment of choice; dosed on booking weight, once or twice daily
• Enoxaparin 1 mg/kg BD or 1.5 mg/kg OD; dalteparin 100 IU/kg BD or 200 IU/kg OD; tinzaparin 175 IU/kg OD
• Increased renal clearance in pregnancy leads some to favour twice daily dosing
• Continue for the remainder of pregnancy and into the postnatal period
• Fully anticoagulated women should be managed in a consultant led clinic with obstetric medicine or haematology input

• IV infusion is preferred if delivery may occur within 24 h, if the woman is acutely unwell or at high risk of bleeding, or with severe renal impairment
• APTT 6 h after the loading dose then at least daily; target ratio 1.5 to 2.5

• Active bleeding or high bleeding risk e.g. placenta praevia
• Bleeding diathesis or acquired coagulopathy
• Thrombocytopenia (platelets <75 x10⁹/L) or HIT
• Acute stroke within 4 weeks
• Severe liver disease with prolonged PT
• Uncontrolled hypertension (>200 mmHg systolic or >120 mmHg diastolic)
• Allergy

• Reserved for women who cannot be anticoagulated or who have recurrent VTE despite adequate anticoagulation
• Significant risks: mortality 0.12 to 0.3%, filter migration in >20%, fracture or IVC perforation in 5%

• May present with shock or cardiac arrest: resuscitate with left lateral uterine displacement and modified ALS
• Consultant led MDT decision (obstetrics, anaesthesia, haematology) on IV UFH versus thrombolysis
• IV UFH is the anticoagulant of choice due to its rapid onset
• Thrombolysis is indicated for life-threatening PE with haemodynamic compromise; start IV UFH promptly afterwards
• Maternal and fetal bleeding risk with thrombolysis is approximately 2 to 3%, similar to non-pregnant patients
• Convert to LMWH once stable

• ↑ plasma volume: ↑ volume of distribution of water soluble drugs; ↓ peak and steady state concentrations
• ↑ renal blood flow and GFR by the second trimester: faster clearance of renally excreted drugs (including LMWH)
• ↓ albumin: ↑ free fraction of protein bound drugs

• Enoxaparin volume of distribution and clearance each increase by approximately 50%
• Peak anti-Xa activity and overall exposure are lower than in non-pregnant women
• Anti-Xa activity 6 to 8 h after a dose in pregnancy may be comparable to 12 h after a dose outside pregnancy; this is reassuring but current timing recommendations are not shortened on this basis

• Lower and earlier peak plasma heparin concentrations than in non-pregnant women
• Blunted APTT response at term due to ↑ factor VIII, ↑ fibrinogen and ↑ binding to non-specific proteins: the APTT may underestimate heparin effect

• No test reliably predicts the risk of vertebral canal haematoma
• APTT: widely available and used for UFH, but insensitive to LMWH and reference ranges vary
• Anti-Xa: an undetectable level is reassuring, but the safe threshold is unknown and it is not always available 24/7
• TEG/ROTEM: rapid, but safe ranges for neuraxial blockade on thromboprophylaxis are not established
• For LMWH, decisions are therefore based on time since the last dose rather than laboratory tests
• Check platelets before neuraxial blockade if UFH has been given for >4 days (HIT)

• 1 mg neutralises 100 U of heparin; half-life approximately 7 min, so SC heparin may need repeated doses
• Fully reverses UFH; only 60 to 80% reversal of LMWH
• Use to facilitate neuraxial blockade has not been studied; consider only when UFH must be urgently reversed

• Hypotension from histamine release; anaphylaxis
• Pulmonary hypertension; non-cardiogenic pulmonary oedema
• Anticoagulant effect in excess (thrombocytopenia, platelet dysfunction, reduced thrombin effect)

• The most feared complication; may cause permanent paralysis if not diagnosed and decompressed within approximately 12 h
• Obstetric incidence is very low (approximately 1 in 200,000 to 250,000) compared with 1 in 3,600 in elderly female orthopaedic patients
• NAP3: permanent harm from vertebral canal haematoma 1 in 140,000; no obstetric cases
• Systematic review found no obstetric cases after neuraxial blockade in women receiving thromboprophylaxis, although the denominator is unknown
• Most reported cases involve abnormal coagulation at the time of insertion or catheter removal: both carry risk

• Guidelines are largely extrapolated from non-obstetric patients and do not account for the hypercoagulable state of pregnancy
• The Association of Anaesthetists/OAA/RA-UK guidance stratifies the risk of neuraxial blockade and asks the anaesthetist to weigh it against the risk of the alternative, usually GA
• Decisions should be individualised and shared with the woman

Time from last dose to neuraxial insertion; adapted from the Association of Anaesthetists 2013 guideline

• Anaesthetic review of women on antenatal LMWH, ideally by 36 weeks (earlier if delivery is likely)
• Plan agreed between obstetrics, anaesthesia, haematology/obstetric medicine and the woman, and documented in the notes with an alert on the record
• The plan should cover when to stop anticoagulation, timing and mode of delivery, analgesic and anaesthetic options, and when to restart
• Accept that some women will need to deliver at short notice despite planning

• Indication for anticoagulation, agent, dose (prophylactic or therapeutic) and timing of the last dose
• Airway assessment and other comorbidities: these alter the balance between neuraxial and general anaesthesia
• Renal function and weight

• FBC (platelets if on UFH >4 days), coagulation screen, renal function
• Group and save

• Advise the woman to omit her next LMWH dose if she thinks she is in labour, has ruptured membranes or has vaginal bleeding, and to contact the unit
• Planned induction or caesarean section can be timed around dosing: e.g. omit the evening dose of prophylactic LMWH before a morning procedure
• Therapeutic LMWH: stop 24 to 36 h before planned induction; very high risk women may be converted to IV UFH, which can be stopped 4 to 6 h before delivery
• SOAP (US) guidance suggests considering a switch to low dose UFH at around 36 weeks in women at high risk of urgent delivery or with a difficult airway; this is less common in UK practice

• Prophylactic LMWH: ≥12 h from last dose to insertion or catheter removal
• Therapeutic LMWH: ≥24 h from last dose
• Prophylactic SC UFH: ≥4 h (some guidance 4 to 6 h)
• IV UFH: stop for ≥4 to 6 h and confirm a normal APTT
• Warfarin: INR ≤1.4


• The same intervals apply to removal of an epidural catheter

• Weigh the risk of neuraxial blockade against that of GA for the individual woman, considering urgency, risks of general anaesthesia (e.g. airway difficulties) and timing/dose of last anticoagulant
• Single shot spinal is generally considered lower risk than an epidural catheter
• Protamine can reverse UFH if needed; it only partially reverses LMWH

• Avoid leaving an epidural catheter in women who will need therapeutic anticoagulation while it is in place
• Mechanical thromboprophylaxis intraoperatively
• Anticipate higher blood loss and wound haematoma risk; ensure uterotonics and blood products are available

• Prophylactic LMWH
• First dose can be given >4hrs after neuraxial blockade/epidural catheter removal provided there is no ongoing bleeding; most units use 6hrs
• Can be given with an epidural catheter in situ BUT the catheter should only be removed >12hrs following the last dose of LMWH
• Should only be given at least 4hrs after epidural catheter removal


• Therapeutic LMWH
• Typically wait 24hrs to reduce risk of PPH and wound haematoma
• Not suitable to give if epidural catheter in situ


• Timing should be agreed with the obstetric team, balancing risks of haemorrhage against thrombosis
• Warfarin can be started from day 5 to 7 postnatally in women needing long term anticoagulation; heparins and warfarin are safe in breastfeeding

• Intermediate risk: at least 10 days
• High risk: 6 weeks

• A failure to straight leg raise 4hrs after a spinal or last epidural dose, or during labour with epidural analgesia, is concerning for evolving neuraxial haematoma
• Other signs include new/severe back pain, progressive numbness/weakness, bladder/bowel dysfunction
• Treat as an emergency: urgent MRI and neurosurgical referral via a defined pathway
• Inform women of warning signs and who to contact

• Check anticoagulant timing before postpartum procedures such as an epidural blood patch or tubal ligation