Venous thromboembolism in pregnancy and the puerperium

• A clot in the leg veins or in the lung (VTE) is one of the leading causes of maternal death. In pregnancy and the weeks after delivery the chance of VTE is four to six times the usual background risk. ^[1][3]
• The absolute risk is still low, about 1 to 2 per 1,000 pregnancies, and about 80% of these clots are venous. ^[1][3]
• Every pregnant woman should have her VTE risk written down before booking, and again if she is admitted or anything changes, and again in labour or straight after delivery. ^[1]
• For a woman with enough risk factors, prevention is low-molecular-weight heparin (LMWH) by injection: either through pregnancy, or from 28 weeks, or for at least 10 days after delivery, depending on how many risk factors she has. ^[1]
• LMWH is also the first-line treatment of an acute clot in pregnancy, in doses calculated from her booking weight, continued for the rest of the pregnancy and for at least 6 weeks after birth and at least 3 months in total. ^[2]
• In pregnancy D-dimer is not used to diagnose VTE; diagnosis rests on compression ultrasound of the leg and, when a PE is suspected, a V/Q scan or CT pulmonary angiogram. ^[2]

By the end of this page you should be able to:

1. State how VTE risk changes in pregnancy and the puerperium and which risk factors RCOG lists.
2. Stratify a woman antenatally and postnatally and choose the timing and duration of LMWH prophylaxis.
3. Prescribe the prophylactic and therapeutic doses of LMWH used in pregnancy, including around delivery and in labour.
4. Investigate a suspected DVT or PE in pregnancy without using D-dimer.
5. Treat acute VTE in pregnancy, including massive PE and the postnatal plan.
6. Explain the typical timing of prophylaxis, the limits of evidence, and how to counsel a woman about breastfeeding, warfarin and NOACs.

A useful way to think about it is location rather than mechanism: the same condition can be a silent leg clot, an acutely painful swollen leg, or a sudden PE with breathlessness and collapse. The distinction matters for how we image it, because leg ultrasound answers the question for DVT while breathlessness or chest pain leads down the PE pathway below. ^[2]

VTE is a leading direct cause of maternal death in the United Kingdom and one of the leading causes of maternal death in the United States. ^[1][3]

• Overall incidence: about 1 to 2 per 1,000 pregnancies; roughly 107 per 100,000 person-years in the UK. ^[1] An antenatal PE is reported at about 1.3 per 10,000 maternities in the UK. ^[1]
• Increased risk: four to six times the background risk in pregnancy, and five times greater still in the puerperium than antepartum. ^[1][3]
• Timing: the risk rises with gestation, reaches its maximum just after delivery, and is concentrated in the first 3 weeks postpartum, when the absolute rate reached about 421 per 100,000 person-years (a 22-fold increase). ^[1]
• Where clots happen: about 80% of thromboembolic events in pregnancy are venous. ^[3]
• Severity: VTE accounts for 9.3% of all maternal deaths in the United States. ^[3]
• PE prevalence among suspects: in pregnant women with suspected PE, only 2 to 6% actually have a PE. ^[2]

Pregnancy is a prothrombotic state for three overlapping reasons, the classic triad of stasis, hypercoagulability and vascular injury:

1. Stasis: growing uterus compresses the pelvic veins, and venous capacitance rises.
2. Hypercoagulability: pregnancy raises several clotting factors and depresses natural anticoagulants, so the balance shifts towards clotting.
3. Vascular injury: delivery, especially instrumental delivery and caesarean section, can injure pelvic vessels.

RCOG lists the risk factors below and groups them as pre-existing, obstetric and new-onset or transient. ^[1] A woman is scored by how many current risk factors she has at that moment, because the transient ones come and go.

Counselling on smoking: women who smoke and are pregnant are counselled to stop, which also reduces VTE risk among other benefits. ^[1]

RCOG also makes risk assessment a repeating process rather than a single box-tick: it must be done prepregnancy or early pregnancy, again on every admission, and again intrapartum or immediately postpartum, because many risk factors are transient and appear late. ^[1]

Pregnancy-related clots can occur anywhere along the venous tree, but the distribution is distinctive: iliac and left femoral involvement is common, often with pelvic vein extension. That is why an ultrasound that only checks the calf can miss the problem, and why compression ultrasound in pregnancy covers the whole proximal leg and the iliac segment. ^[2]

A previous VTE is the dominant driver. It is described as having an odds ratio of about 24.8 for recurrence in a large retrospective study, and the risk in pregnancy is a temporary rise: one study found recurrence rates of 10.9% during pregnancy against 3.7% outside it, giving a relative risk during pregnancy of 3.5. ^[1] Recurrence is treated as a separate management problem from risk-factor counting, and it is addressed on its own below.

Most women who develop VTE in pregnancy have symptoms. ^[2] The picture depends on where the clot sits:

• Leg DVT: usually unilateral leg pain and swelling, and lower abdominal pain when the clot extends into the pelvic veins or a collateral circulation develops. ^[2]
• Pulmonary embolism: dyspnoea, chest pain, haemoptysis and collapse. A low-grade fever and a raised white cell count can occur and mimic infection. ^[2]

Because the pregnant body adapts (rising minute ventilation, faster heart rate, leg swelling in late pregnancy), the signs are notoriously unreliable: a pregnant woman's clinical assessment of DVT or PE is only correct a minority of the time, and many suspected PEs in pregnancy are not PE. ^[2]

The common look-alikes are worth keeping in front of you, because treatment with LMWH is started before the diagnosis is confirmed:

• Leg swelling from pregnancy or pelvic pressure: symmetric, no tenderness, often in late pregnancy.
• Muscle injury or Baker's cyst: usually one well-defined area, no systemic symptoms.
• Cellulitis or venous thrombophlebitis: hot, red, with infection markers.
• Breathlessness from pregnancy, anaemia, cardiac or lung disease rather than PE.
• Pneumonia, pneumothorax, musculoskeletal chest pain.
• Aortic dissection in the chest-pain category; it can also widen the mediastinum on chest X-ray. ^[2]

The guiding rule from RCOG is simple: if VTE is suspected, start LMWH straight away, in parallel with organising objective testing, unless there is a strong reason not to (active bleeding or major bleeding risk). Do not wait for a test result before giving the first dose. ^[2]

D-dimer is not used in pregnancy. RCOG states explicitly that D-dimer testing should not be performed in the investigation of acute VTE in pregnancy. ^[2] The reason is that D-dimer rises physiologically through pregnancy and is high fairly early, so a raised value means nothing and a normal value does not exclude a clot. Studies quoted in the guideline show D-dimer levels rising with gestational week and differing between singleton and multiple pregnancy. ^[2] In short, there is no D-dimer cut-off that safely excludes VTE in pregnancy, and both RCOG and the studies it cites treat D-dimer as unhelpful here. ^[2]

Compression duplex ultrasound is the first test for a suspected DVT. ^[2]

• If it is positive, treat and carry on.
• If it is negative and clinical suspicion is low, LMWH can be stopped.
• If it is negative but clinical suspicion is high, LMWH is stopped and the ultrasound repeated on days 3 and 7; a negative repeat excludes DVT in that group, with a negative predictive value of 99.5%. ^{[2] [1]}

A normal leg ultrasound cannot exclude a PE, but iliac vein and pelvic extension should be considered when the presentation is back or buttock pain with whole-limb swelling. ^[2]

A pregnant woman with suspected PE should have an electrocardiogram and chest X-ray first. ^[2]

• If she also has symptoms or signs of a DVT, do compression duplex ultrasound; if it is positive, treat and no further imaging is needed. ^[2]
• If there are no DVT symptoms or signs, a V/Q scan or a CT pulmonary angiogram (CTPA) is performed. ^[2]
• If the chest X-ray is abnormal and PE is still suspected, prefer CTPA. ^[2]
• If either test is normal but suspicion remains high, alternative or repeat testing is carried out, and treatment is continued in the meantime. ^[2]

The choice between V/Q and CTPA is a balance of radiation risks. V/Q scanning is generally favoured as first line in pregnancy because of its high negative predictive value and lower radiation dose to the breasts; CTPA uses more breast radiation but less fetal radiation. The fetal dose is of the order of 0.1 milli-gray for CTPA and 0.5 milli-gray for V/Q scanning, well below levels associated with teratogenicity. ^[2]

Women should be told plainly that V/Q scanning may carry a slightly higher risk of childhood cancer while CTPA carries a higher risk of maternal breast cancer, but that both absolute risks are very small, and should be involved in the choice where that is feasible. ^[2]

There is no validated pre-test probability score for VTE in pregnancy, so scoring systems validated in non-pregnant patients are not relied on, and RCOG is explicit that there is no evidence to support their use here. ^[2]

For women without previous VTE or thrombophilia, RCOG bases prophylaxis on the count of current risk factors. ^[1]

• Four or more current risk factors: consider prophylactic LMWH throughout pregnancy; these women usually continue it for 6 weeks postnatally, with a postnatal reassessment. ^[1]
• Three current risk factors: consider prophylactic LMWH from 28 weeks; again usually 6 weeks postnatally, with reassessment. ^[1]
• Two current risk factors: consider prophylactic LMWH for at least 10 days after delivery. ^[1]
• Admitted to hospital while pregnant (including for hyperemesis or ovarian hyperstimulation syndrome): usually offer LMWH while in hospital unless there is a reason not to, such as risk of delivery or active bleeding. ^[1]

Risk assessment is repeated at any admission, if the woman develops new problems, and intrapartum or immediately postpartum. ^[1]

First-trimester risks: hyperemesis is treated with LMWH while it lasts; ovarian hyperstimulation syndrome in the first trimester is treated with LMWH; and an IVF pregnancy with three other risk factors starts LMWH in the first trimester. ^[1]

LMWHs are the agents of choice for both antenatal and postnatal prophylaxis. ^[1]

• Dose by weight: the booking or most recent weight is used. ^[1]
• No platelet count monitoring is needed unless the woman has had prior exposure to unfractionated heparin. ^[1]
• No anti-Xa monitoring is needed for prophylaxis. ^[1]
• Reduce the dose in renal impairment: lower doses if creatinine clearance is under 30 ml per minute for enoxaparin and dalteparin, or under 20 ml per minute for tinzaparin. A creatinine clearance of 30 ml per minute corresponds to a serum creatinine of about 200 micromol per litre in a 30-year-old woman weighing 70 kg. ^[1][2]
• LMWH is safe in breastfeeding. ^[1]
• NOACs and warfarin are avoided in pregnancy; after delivery LMWH is converted to warfarin only after the risk of haemorrhage is reduced, usually 5 to 7 days. ^[1]
• Aspirin is not recommended for thromboprophylaxis in obstetric patients. ^[1]

High prophylactic, that is twice-daily, dosing is used only in the situations in which RCOG separates it out (for example with intrapartum or treatment contexts in 37b); for routine prophylaxis the once-daily row above is used. ^[1]

This is the highest-risk group and it is handled as its own problem rather than folded into the simple count. ^[1]

• One previous VTE: offer LMWH prophylaxis throughout pregnancy for any previous VTE except one provoked by major surgery with no other risk factors. All women with previous VTE still receive at least 6 weeks of postpartum prophylaxis. ^[1]
• Provoked by major surgery only, fully recovered, no other factors: LMWH can be withheld until 28 weeks, with careful surveillance for new factors. ^[1]
• Unprovoked, or related to oestrogen (contraception or pregnancy), or related to a non-surgical transient factor, or with other risk factors: LMWH throughout pregnancy. ^[1]
• Previous recurrent VTE, or VTE with antithrombin deficiency or antiphospholipid syndrome: higher-dose LMWH (50%, 75% or full treatment dose) antenatally and for at least 6 weeks postpartum or until returned to oral anticoagulation, under specialist care. ^[1]
• Antithrombin deficiency on LMWH: aim for 4-hour peak anti-Xa levels of 0.5 to 1.0 IU per mL with an assay that does not use exogenous antithrombin. ^[1]
• Long-term warfarin or NOAC at conception: stop oral anticoagulants and convert to LMWH as soon as pregnancy is confirmed, ideally within 2 weeks of the missed period and before 6 weeks of gestation; or start LMWH as soon as a pregnancy test is positive if not on warfarin. ^[1]
• Asymptomatic heritable thrombophilia: treated by stratum. Antithrombin, protein C or protein S deficiency, or more than one thrombophilic defect (homozygous factor V Leiden, homozygous prothrombin mutation, compound heterozygotes), are higher risk and referred for antenatal prophylaxis and 6 weeks' postnatal prophylaxis. Heterozygous factor V Leiden or prothrombin mutation, or antiphospholipid antibodies, count as risk factors: with three other factors prophylaxis throughout pregnancy, with two other factors from 28 weeks, and with one other factor 10 days postnatal prophylaxis. ^[1]

Previous VTE carries a recurrence rate in pregnancy of 2 to 11% and a relative risk during pregnancy of 3.5, so LMWH is continued even when the patient feels well. ^[1]

The points that matter at the bedside are these: ^[1]

• A woman on LMWH should not inject once labour starts or if there is any vaginal bleeding; she should be reassessed on admission.
• Regional techniques should be avoided until at least 12 hours after the last prophylactic LMWH dose, 24 hours after a therapeutic dose. ^[1]
• LMWH is not given for 4 hours after spinal anaesthesia or after the epidural catheter is removed; the catheter is not removed within 12 hours of the most recent injection. ^[1][2]
• For elective caesarean on prophylactic LMWH: give a dose the day before, omit the morning dose on the day, and do the operation that morning; restart as soon as possible after delivery if there is no postpartum haemorrhage and regional analgesia was not used. ^[1]
• If haemorrhage risk is high, use anti-embolism stockings, foot impulse devices or intermittent pneumatic compression, and consider unfractionated heparin (UFH).
• If bleeding develops on LMWH, stop it and obtain specialist haematological advice.

• Class 3 obesity (BMI 40 kg/m2 or more): prophylactic LMWH, weight-adjusted, for 10 days after delivery for all women in that category. ^[1]
• Two or more persisting risk factors after delivery: prophylactic LMWH for 10 days. ^[1]
• Any woman who has had a caesarean section: LMWH for 10 days after delivery, except after an elective caesarean section, where 10 days is offered only if additional risk factors are present. ^[1]
• High-risk women: LMWH for 6 weeks; intermediate-risk women: 10 days. ^[1]
• Risk that persists beyond 10 days postpartum (prolonged admission, wound infection, surgery in the puerperium) extends prophylaxis up to 6 weeks or until the extra risk factor has resolved. ^[1]

When VTE is diagnosed, or strongly suspected pending testing, LMWH is the treatment. ^[2]

• Start immediately: treat first, test in parallel.
• Table below gives doses by booking or early pregnancy weight, once daily or in two divided doses; decide according to local protocol. There is insufficient evidence to recommend one schedule over the other. ^[2]
• Around delivery, UFH or induction may be used to shorten the gap off anticoagulation because the half-life is shorter. ^[2]

• Routine peak anti-Xa is not recommended except at extremes of weight (under 50 kg or 90 kg or more) or with complicating factors (renal impairment or recurrent VTE). ^[2]
• Where monitoring is used, the target peak anti-Xa 3 hours post-injection is 0.5 to 1.2 IU per mL (0.5 to 1.0 IU per mL if 4 hours post-dose in antithrombin deficiency). ^[2]
• Routine platelet counts are not carried out. ^[2]
• Baseline bloods before starting: full blood count, coagulation screen, urea and electrolytes, liver function tests. ^[2]

LMWH is continued at therapeutic doses for the rest of the pregnancy and for at least 6 weeks after delivery and until at least 3 months of treatment have been given in total. ^[2] She is taught to self-inject; adherence falls a little postnatally, so reinforce it at follow-up. ^[2]

• Vitamin K antagonists such as warfarin are not used antenatally because they cross the placenta. ^[2]
• LMWH or an oral anticoagulant may be used postnatally, with a choice discussed. ^[2]
• Postpartum warfarin is avoided until at least day 5, and longer if the woman is at increased risk of postpartum haemorrhage. ^[2]
• Heparin (unfractionated or LMWH) and warfarin are not contraindicated in breastfeeding. ^[2]
• Newer oral agents have not been studied in pregnancy and are avoided; fondaparinux, argatroban or recombinant hirudin are considered only when heparin or danaparoid cannot be used. ^[2]

Massive PE is a medical emergency. ^[2]

• Immediate multidisciplinary assessment including the on-call consultant obstetrician.
• Intravenous unfractionated heparin is the preferred initial treatment for massive PE with cardiovascular compromise, starting at 80 units per kg, then 18 units per kg per hour, with APTT target 1.5 to 2.5 times the control value, or anti-Xa 0.35 to 0.7 units per mL (0.5 to 1.0 units per mL in life-threatening PE). ^[2]
• Thrombolysis should be considered; in one analysis of massive PE, thrombolysis reduced the rate of recurrent PE or death from 19.0% with heparin alone to 9.4% (OR 0.45, 95% CI 0.22 to 0.90). Reported maternal bleeding with thrombolysis is about 2.9% and fetal loss about 1.7%, with no maternal deaths reported. ^[2]
• If none of these are suitable, cardiothoracic surgery for surgical embolectomy is considered.
• Cardiac arrest in pregnancy: resuscitate with the woman in a left lateral tilt and, if resuscitation is unsuccessful by 5 minutes and the pregnancy is over 20 weeks, perform perimortem caesarean section. ^[2]
• An urgent echocardiogram or CTPA is arranged within 1 hour of presentation when massive PE is suspected. ^[2]

When a woman receiving treatment-dose LMWH goes into labour or has a planned delivery: ^[2]

• Once labour begins, she should not inject any further heparin.
• For an elective delivery LMWH is discontinued 24 hours beforehand, UFH 12 hours beforehand if subcutaneous or 6 hours if intravenous. ^[2]
• Regional anaesthesia is not used until at least 24 hours after the last therapeutic LMWH dose. ^[2]
• LMWH is not given for 4 hours after spinal anaesthesia or after the epidural catheter is removed, and the catheter is not removed within 12 hours of the most recent injection.
• At elective caesarean, omit treatment doses for 24 hours, give a prophylactic LMWH dose 4 hours post-operatively, and restart the treatment dose 8 to 12 hours later. ^[2]
• Wound drains (abdominal and rectus sheath) and interrupted skin sutures are considered at caesarean to allow drainage of any haematoma.
• A woman at high bleeding risk who still needs anticoagulation receives intravenous UFH until the bleeding risk settles.

• Recurrence: the risk of a further clot in pregnancy or the postpartum period after a first VTE is raised (2 to 11% quoted), so full therapeutic treatment is maintained. ^[1][2]
• Post-thrombotic syndrome: reported in about 42% after DVT in pregnancy; prolonged LMWH (over 12 weeks) is associated with a lower rate, and graduated compression stockings with ankle pressure over 23 mmHg are advised on the affected leg. ^[2]
• Heparin allergy: cross-reactivity between LMWH preparations is about 33%; danaparoid may be used in such women. ^[2]
• Skin reactions: heparin-induced delayed-type hypersensitivity in about 20% of treated women in one prospective study. ^[2]
• Osteoporosis: very much less with LMWH than with UFH (0.04% versus about 2%). ^[2]
• Heparin-induced thrombocytopenia: rare with LMWH, and far commoner with UFH; routine platelet monitoring is not required with LMWH alone. ^[2]

Primary prevention amounts to identifying women at risk and acting before the clot happens. Because many VTEs occur before the routine antenatal booking visit, and 40 to 50% of antenatal clots occur before 15 weeks, the first risk assessment should be prepregnancy if at all possible. ^[1]

• Screen everyone at least once, and again on admission, in labour or immediately postpartum. ^[1]
• Combine the count-based rule (four, three or two risk factors) with the separate, more intensive rules for previous VTE and thrombophilia. ^[1]
• Use LMWH rather than aspirin, warfarin or NOACs for prophylaxis. ^[1]
• Consider anti-embolism stockings (graduated compression with a calf pressure of 14 to 15 mmHg) and mechanical devices for women in whom LMWH is contraindicated. ^[1]
• Consider a temporary inferior vena cava filter in the peripartum period for iliac vein thrombosis or for recurrent PE despite adequate anticoagulation. ^[2]

For women who have had a VTE in a previous pregnancy, general advice for future pregnancies and other high-risk times is given at postnatal review; thrombophilia testing is only done once anticoagulation has stopped and only if the result would change future management. ^[2]

• The diagnosis is clinical plus ultrasound: a whole-leg and iliac ultrasound is more important than any blood test, and D-dimer is unhelpful in pregnancy. ^[2]
• Compression ultrasound, and V/Q or CTPA, may not be available everywhere; if diagnosis is suspected strongly, start LMWH while arranging referral. ^[2]
• Unfractionated heparin can be used where LMWH is not available or where its shorter half-life is needed; it should be given intravenously for massive PE, and with APTT monitoring 4 to 6 hours after the loading dose. ^[2]
• Mechanical prophylaxis (anti-embolism stockings, foot pumps, intermittent pneumatic compression) is the practical alternative where LMWH is contraindicated or unavailable, and is cheap relative to its benefit. ^[1]
• Warfarin is inexpensive and useful postpartum once bleeding risk has settled, though not for just 10 days of prophylaxis; it requires monitoring and drug interactions. ^[1][2]
• Postnatal follow-up matters: a clot managed in hospital may be followed by weeks of self-injection; community support for injection technique and safe disposal of sharps is part of the treatment. ^[2]

Pulmonary embolism, deep vein thrombosis, normal pregnancy physiology, gestational hypertension and pre-eclampsia, caesarean section, postpartum haemorrhage, thrombophilia, anticoagulant and antiplatelet drugs, and maternal collapse should be read alongside this page.