Pulmonary embolus in pregnancy

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Available online at www.sciencedirect.com

www.elsevier.com/locate/semperi

Pulmonary embolus in pregnancy Jennifer C. Donnelly, MDn, and Mary E. D'Alton, MD Department of OB/GYN, Columbia University Medical Center, 622 West 168th St, PH 12-32, New York, NY 10032

AR T IC LE INFO

abstra ct Venous thromboembolism remains in the top three leading causes of maternal death in

Keywords:

the US, representing 10.2% of pregnancy-related deaths. Risk of developing a pulmonary

Venous thromboembolism

embolus appears to increase throughout pregnancy, with a peak in incidence in the early

Low molecular weight heparin

postpartum period. Overall the incidence of VTE is 0.6–1.8 VTEs per 1000 deliveries.

Antocoagulation

Diagnosis and management of pulmonary embolus can prove challenging, but the aim should be to optimize maternal outcome while minimizing hemorrhagic complications. Low-molecular-weight heparin is a safe and effective treatment for the majority of cases of pregnancy-related pulmonary embolus. & 2013 Elsevier Inc. All rights reserved.

Venous thromboembolism (VTE), which is comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), remains one of the leading causes of maternal death in the developed world.1 It is represented in the leading causes of maternal death in both the US and the UK.2,3 A nationwide review of death certificates carried out by the Pregnancy Mortality Surveillance System showed that VTE increased as a cause of death in the US between 1998 and 2005 represented 10.2% of pregnancy-related deaths.2 Thromboembolism was the leading cause of direct maternal death in the United Kingdom in the 1990s and despite a reduction in overall numbers, it still appears as a major cause of maternal death according to the Confidential Enquiry into Maternal Deaths in the UK.3 VTE risk increases significantly during pregnancy and in the postpartum period. Virchow's triad of hypercoagulability, hemodynamic changes, and endothelial injury represents three main factors that when present give the ideal environment for development of thrombosis. Pregnancy provides a good example of when all these factors are physiologically present. Diagnosis of PE can be challenging during pregnancy, as symptoms of pregnancy can mimic those of either PE or DVT. Consequently, it is critical that all clinicians remain vigilant to the possibility of VTE arising in this patient population. Prevention, diagnosis, and management of VTE n

in pregnancy have been the subject of several recent guidelines and consensus statements.4–8 Local guidelines should address ways in which VTE risk in pregnant women can be minimized. Specialized obstetric and hematological advice should be sought early to guide management of pregnant women with VTE.

1.

Incidence

Precise and consistent estimates of absolute risk of VTE in the antepartum and postpartum periods vary in the literature. Four studies that compared pregnancy risk to non-pregnant risk9–12 confirmed a significantly increased risk of venous thromboembolism related to pregnancy compared to that outside of the antepartum and postpartum period with an approximate incidence of 0.6–1.8 VTEs per 1000 deliveries (Table 1). Further refinement of risk is of great importance in order to identify those who would benefit most from thromboprophylaxis and to avoid unnecessary use of anticoagulation in low-risk periods. Earlier studies focused on the differences in rates of VTE that occurred antepartum compared to postpartum and the influence that the type of thromboembolic event (either PE or DVT) had on their frequencies.10,13–16 Different authors have used different

Corresponding author. E-mail address: [email protected] (J.C. Donnelly).

0146-0005/13/$ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.semperi.2013.04.002

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Table 1 – Summary of study characteristics and inclusion criteria. References

Date range

Database used

ICD Classification

Inclusion gestation

Included miscarriage/ TOP

Postpartum follow-up

Andersen et al.13

1984–1994

ICD 8 and 10

All

Yes

8 weeks

Gherman et al.14

1978–1996

None

All

N/A

6 weeks

Lindqvist et al.15

1990–1993

ICD 9

All

N/A

6 weeks

Salonen Ros et al.10

1987–1995

ICD 9

427 weeks

No

1 year

Simpson et al.16

1988–1997

ICD 9

424 weeks

No

Until discharge

Heit et al.9

1966–1995

None

412 weeks

412 weeks

12 weeks

James et al.1

2000–2001

ICD 9

All

N/A

Yes - NOS

Jacobsen et al.17 Liu et al.18

1990–2003 1991–2006

ICD 9 and 10 ICD 9 and 10

423 weeks N/A

no N/A

12 weeks Yes–NOS

Virkus et al.12 Sultan et al.11

1995–2005 1987–2004

County based Hospital Discharge Registry Single institution Hospital Discharge Registry Swedish National Birth Registry Swedish National Birth Registry and inpatient register Single institution Maternity Information System County based medical records linkage system National inpatient sample National patient register National hospital discharge register National person registry National general practice registry

ICD 10 None

N/A All

N/A No

12 weeks 12 weeks

ICD ¼ International Classification of Disease; TOP ¼ termination of pregnancy; N/A ¼ not available; NOS ¼ not otherwise specified.

descriptors to report their results, some using risk per pregnancy16–18 or delivery,1,10,13–15,19,20 and others reporting risk per person years9,11 (Table 2). Different methods have been used to ascertain data, with some groups using ICD coding1,10,12,13,15–18 and others using population databases9,11,14,19 making direct comparisons difficult (Table 1). However, despite differing ranges, they provide a useful framework to calculate risk, with an approximate incidence of 0.6–1.8 VTEs per 1000 deliveries. Some previous studies reported a highest incidence rate of VTE in the antepartum period13,20 while others reported an increased rate around the time of delivery including the early postpartum period.9,17 The majority of studies classified by gestational age show a clustering of risk around the puerperium.10–12 A recent population-based Danish study classified the incidence of VTE according to weeks of gestation and showed a significant rise in incidence in the third trimester, a peak following delivery and a steep decline to a pre-pregnancy incidence at 12 weeks postpartum.12 Accurate assessment of the risk in early pregnancy is difficult as many studies exclude early pregnancy losses or only report outcomes from 24 weeks onwards.10,16,17,19 Sultan reported that women in their third trimester of pregnancy were at 6.1-fold (95% confidence interval 4.7–7.9) increased risk of first VTE compared to those outside of pregnancy.11 They found that the risk in the first and second trimesters conferred little increased risk (1.6 and 2.1 respectively). They reported that the first 6 weeks postpartum was associated with a 22-fold increase in risk, with the peak occurring within the first 3 weeks.11 In the United Kingdom, the Centre for Maternal and Child Enquires' (CMACE) confidential report of maternal death for

2006–2008 reported a maternal mortality rate of 0.79 per 100,000 maternities due to VTE.3 This figure calculated based on 18 reported deaths, 16 of which were due to pulmonary embolism.3 A large American population study reported a case fatality rate of 2.4% related to PE. They reported 73 deaths among the 3009 women with a PE in a population of over 8 million.1 This is comparable to the maternal mortality rate reported in the UK. Pulmonary embolus was also reportedly the cause of 10.2% of pregnancy-related mortality in the United States between 1998 and 2005, as reported by the CDC's Division of Reproductive Health, Pregnancy Mortality Surveillance System.2

2.

Risk factors

The Royal College of Obstetricians and Gynecologists (RCOG) in the United Kingdom (UK) recommends that all women should undergo a risk assessment of risk factors for venous thromboembolism in early pregnancy.21 Women at high risk, such as those with a previous VTE, should be offered prepregnancy counseling in order to formulate a plan for thromboprophylaxis during pregnancy. Low-molecularweight heparins (LMWHs) are the agents of choice for antenatal thromboprophylaxis.8,21 The RCOG recommend that all women with 3 or more current or persisting risk factors, as outlined in Table 3, should be considered for antenatal thromboprophylaxis (Table 4). Risk should be risk stratified into low, moderate, and high. All women should be reassessed again following delivery and those with two or more persisting risk factors should be considered for LMWH

– 40% – – 24 4/24 – 0.06 – – – 2 38 90 – 42 24 3009 – 2144 – – Andersen et al. Gherman et al.14 Lindqvist et al.15 Salonen Ros et al.10 Simpson et al.16 Heit et al.9 James et al.1 Jacobsen et al.17 Liu et al.18 Virkus et al.12 Sultan et al.11

63,319 268,525 479,422 1,003,489 395,335 50,080 8,330,927 613,232 3,852,569 819,751 972,683

s 165 608 – 359 100 14,335 615 6821 727 220

– – – 0.17 – – 0.36 0.27 0.54 – –

– 60% – – 18 20/24 – 0.22 – – –

Incidence VTE PE PN PE AN Incidence PE/1000 VTE (n) PE (n) Population

13

References

Table 2 – Summary of reported incidence of pregnancy associated venous thromboembolism.

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thromboprophylaxis.21 Some risk factors carry a higher risk of thromboembolism than others as discussed below and demonstrated in Table 2. PE ¼ pulmonary embolus; AN ¼ antenatal; PN ¼ postnatal; VTE ¼ venous thromboembolism. a Maternities represent all pregnancies including miscarriages and terminations. b Deliveries represent livebirths and stillbirths after 24 weeks. c Pregnancy years/puerpural years/postpartum years represent all years that were during pregnancy/first 4 weeks postpartum/first 3 months postpartum in a national registry study.

0.85/1000 deliveries 0.6/1000/1000 deliveriesb 1.3/1000 deliveriesb – 0.85/1000 maternitiesa – 1.72/1000 deliveriesb 1/1000 deliveriesb – – –

0.52 – 0.65 – 0.28/1000 – – – – 1.07/1000 pregnancy yearsc 0.65/1000 pregnancy yearsc

0.33/1000 – 0.65 – 0.65/1000 – – – – 1.75/1000 puerpural yearsc 2.28/1000 postpartum yearsc

E M I N A R S I N

b

VTE ante

VTE post

S

2.1.

Previous thrombosis

The most important risk factor for thrombosis in pregnancy is a previous history of a thromboembolic event.22 The relative risk of recurrent thrombotic events in pregnancy has been calculated as 3.5 (95% CI 1.6, 7.8).23 The use of anticoagulants in this at-risk population appears to reduce the risk of recurrent events, with rates of 2.4–12.2% in pregnant women who did not receive anticoagulants,24,25 compared to 0–2.4% in those who have.25–27 Women who have had an estrogenprovoked VTE (one related to use of the oral contraceptive pill) are at a higher risk of pregnancy-related VTE than those who have had an unprovoked VTE.23,24 Women who have had a single previous VTE associated with a transient risk factor, such as a fracture related VTE, may be considered at lower risk of recurrence antenatally and therefore may be considered for postpartum prophylaxis only.

2.2.

Thrombophilia

The other main significant risk factor for pregnancy-related VTE is thrombophilia. Inherited thrombophilia is found in between 20% and 50% of cases of pregnancy-related VTE.20,28 The American College of Obstetricians and Gynecologists recommend that women with a previous thrombotic event who have not had complete evaluation of possible underlying etiologies should be tested for antiphospholipid antibodies and inherited thrombophilias.7 The type of thrombophilia has an influence on the risk. Women heterozygous for factor V Leiden (FVL) or the prothrombin gene mutation (Prothrombin G20210A) have a roughly 5-fold increased risk of VTE in the general population and in pregnancy,29–31 with an additive risk if there is a positive family history.32 A recent systematic review of prospective studies found that factor V Leiden (FVL) also slightly increased the risk of recurrent VTE (OR 1.39, 95% CI 1.15–1.67).33 Antithrombin, protein C, and protein S deficiency have a higher background risk for thrombosis, which can be as high as 15–50% lifetime risk with antithrombin deficiency.34 Both previous thrombosis and thrombophilia are risk factors that are identifiable prior to pregnancy, allowing risk reduction strategies to be planned prior to and in early pregnancy. Most deaths that occurred in the CMACE report had identifiable risk factors, highlighting the need to apply the evidence that is available in clinical practice.3

2.3.

Age

Age is an important risk factor in the development of VTE in the postpartum period and in the non-pregnant state, but not during the antepartum period.11 Women aged 35 years and over have been shown to have an absolute excess rate of VTE of about 1.6 per 1000 compared to women aged 25–34 years (a 70% relative increase).11

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Table 3 – Risk factors for venous thromboembolism in pregnancy. (Adapted from RCOG Green Top Guideline 37a, Reducing the risk of thrombosis and embolism during pregnancy and the puerperium.21) Onset

Factors

Risk score

Pre-existing

Prior venous thromboembolism Recurrent/unprovoked/estrogen related Previous VTE provoked Thrombophilia Heritable (Antithrombin deficiency, Protein C deficiency, Protein S deficiency; Factor V Leiden, prothrombin gene G20210A) Acquired Persistent lupus anticoagulant, persistent high titer anticardiolipin/ beta2glycoprotein1 antibodies Medical co-morbidities (eg heart or lung disease, SLE, cancer, sickle cell disease, and inflammatory conditions) Age 4 35 Pre/early pregnancy BMI 430 kg/m2 Parity ≥3 Smoking Gross varicose veins Paraplegia

High Moderate Moderate Moderate Low Low Low/moderate Low Low Low Low

Obstetric

Multiple pregnancy, assisted reproductive therapy Pre-eclampsia Cesarean delivery Postpartum hemorrhage 41000 ml Prolonged labor

Low Low Low/moderate Low Low

New onset/ transient

Surgical procedure (e.g., postpartum sterilization, appendicectomy, dilation, and curettage) Hyperemesis, dehydration Ovarian hyperstimulation syndrome Immobility (e.g., ≥3 days bed rest) Systemic infection Long distance travel (≥4 h)

Moderate Low Low Low Low Low

2.4.

Cesarean section

Elective cesarean delivery doubles the risk of VTE, although in a patient with no risk factors, the overall risk is low. Women who have an emergency cesarean delivery have twice the risk compared to elective cesarean deliveries.35 Different guidelines base their recommendations for postpartum thromboprophylaxis on risk factor identification with more aggressive and prolonged treatment for women at higher risk.6–8

2.5.

Obesity

Fourteen out of 18 women who died from thromboembolism in the 2006–2008 CMACE report were overweight.3 Although obesity itself is only a moderate risk factor for the development of VTE, its increasing prevalence in the pregnant population specifically warrants particular attention. Although the data in pregnancy are limited, the risk of VTE appears to increase further with increasing obesity.36

3.

Diagnosis of pulmonary embolus

Clinical suspicion is vital for the diagnosis of pulmonary embolism in pregnancy. Many of the signs and symptoms suggestive of PE are present during normal pregnancy, such

pregnancy, this drops to less than 10%.37 However, if there is a strong suspicion of a thrombus, objective testing should be carried out to confirm or refute the diagnosis and treatment should be started pending the results being available, unless treatment is strongly contraindicated.6,8 Where there is clinical suspicion of a PE, initially, bilateral lower limb Doppler should be performed38 (Fig. 1). The role of Doppler in investigation of PE in pregnancy has not been validated, but there have been several studies that have shown its role in nonpregnant women.39,40 As a diagnosis of deep venous thrombosis (DVT) may indirectly confirm a diagnosis of PE, and as anticoagulant therapy is the same for both conditions, this strategy would limit the amount of radiation doses given to the mother and the fetus. If the Dopplers are negative or non-diagnostic, the second test should be a chest X-ray (CXR). The risk to the fetus from radiation from a CXR is negligible at any stage of pregnancy.41 Chest X-ray may identify other pulmonary diseases such as pneumonia or pneumothorax. While the CXR may be normal in 50% of pregnant women with objectively proven PE, abnormal features may include atelectasis, effusion, focal opacities or pulmonary edema.42 If the CXR is abnormal, a computed tomography pulmonary angiogram (CTPA) should be performed. If the CXR is normal, either CTPA or ventilation perfusion (V/Q) scanning should be performed.6 In nonpregnant patients, CTPA is recommended as the first line

as shortness of breath, tachycardia, and swollen lower limbs.

investigation as it has a better sensitivity and specificity, it

Among nonpregnant women, PE is confirmed in 25% of patients in whom the diagnosis is suspected; however in

can identify other pathology, such as aortic dissection, and provides a lower dose of radiation to the fetus.43 V/Q

E R I N A T O L O G Y

175 units/kg/d 200 units/kg/daily 1.5 mg/kg/daily Postpartum

LMWH ¼ low-molecular-weight heparin; aPTT ¼ activated partial thromboplastin time; INR ¼ international normalized ratio. *= May be given in 2 divided doses.

Target INR 2.0–3.0

– 175 units/kg/d 1 mg/kg/12 hourly Treatment dose Antepartum

100 units/kg/12 hourly

40 mg 12 hourly Intermediate dose

5000 units 12 hourly

4500 units 12 hourly

All trimesters

Gestation based First trimester Second trimester Third trimester 3500 units daily 4500 units daily 7000 units dailyn 9000 units daily 75 units/kg/d 2500 units daily 5000 units daily 7500 units dailyn 10,000 units dailyn 75 units/kg/d 20 mg daily 40 mg daily 60 mg dailyn 80 mg dailyn 0.6 mg/kg/dayn Prophylaxis Weight based (kg) o50 50–90 91–130 131–170 4170

Tinzaparin Dalteparin Enoxaparin

P

10,000 units or more 12 hourly adjusted to mid interval target aPTT (1.5–2.5)

–

E M I N A R S I N

5000–7500 units 12 hourly 7500–10,000 units 12 hourly 10,000 units 12 hourly

– – – – –

Warfarin (postpartum) Unfractionated heparin LMWH Agent

Table 4 – Anticoagulation regimens for prophylaxis and treatment of venous thromboembolism; weight adjusted for LMWH and trimester adjusted for unfractionated heparin. (Adapted from ACOG Practice Guideline,5 ACCP Guideline,6 RCOG Green Top Guideline 37a.21)

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scanning delivers a higher dose of radiation than CTPA, but this can be reduced if perfusion scanning is used alone. V/Q scanning carries a higher lifetime risk of cancer in the offspring than CTPA (1 in 280,000 vs o1 in 1 million) but carries a lower risk of maternal breast cancer.44,45 There is no validated clinical probability scoring system for the diagnosis of VTE in pregnancy.38 Outside of pregnancy, the Wells scoring criteria is used to direct clinical investigation of VTE.46 D-dimers, the smallest degradation product of cross-linked fibrin, are useful for their negative predictive values.19 D-dimer levels increase with the progression of pregnancy due to physiological changes. A low D-dimer level (o250 mcg/l) in pregnancy is likely to suggest that there is no PE, and may provide additional reassurance in the presence of negative compression Doppler studies. However, a positive 37 D-dimer test requires additional testing.

4. Treatment of pulmonary embolus during pregnancy In clinically suspected pulmonary embolus, treatment should be instituted prior to confirmation of the diagnosis. In pregnancy, safety issues for the mother and fetus should be considered. The standard treatment for VTE outside of pregnancy is low-molecular-weight heparin (LMWH) in the acute phase accompanied by warfarin for 3–6 months.38 Warfarin crosses the placenta and is a known teratogen causing a classic embryopathy in 5% of exposed fetuses between 6 and 9 weeks of gestation.47 This is manifested as midface hypoplasia, stippled chondral calcifications, and short proximal limbs. Later in pregnancy, warfarin has been associated with fetal intracranial hemorrhage and schizencephaly. Therefore the use of warfarin is contraindicated in pregnancy in most cases. Neither unfractionated heparin nor LMWH cross the placenta so there is no risk of fetal bleeding or teratogenicity with the use of these treatments. Treatment with LMWH has emerged as the medical treatment of choice for acute PE in pregnant patients and this has been recommended by many guidelines (Table 4).6,8 This is due to the substantial accumulating evidence as to the safety and efficacy of LMWH in pregnant women for the prevention and treatment of VTE.48–51 For many years, unfractionated heparin (UFH) was the standard treatment. The benefits of LMWH include its more predictable pharmacokinetics allowing weight-based dosing without the need for monitoring, a reduced risk of heparin-induced thrombocytopenia and a reduced risk of heparin-induced osteoporotic fractures compared to UFH.51 LMWH should be given in two divided doses with dosages titrated against the woman's most recent weight.52,53 Anti-Xa activity measurement is not required routinely except on women at extremes of body weight or with complicating factors such as renal impairment.51 Treatment with therapeutic doses of subcutaneous LMWH should be continued for the remainder of the pregnancy. In massive life-threatening PE, intravenous unfractionated heparin is the treatment of choice due to its rapid effect and the experience in its use. Where there is hemodynamic compromise, there is a case for considering therapy with a

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Suspected pulmonary embolus Begin LMWH Bilateral compression ultrasonography Positive

Negative

Connue LMWH

Chest X-Ray

Normal CTPA/V/Q scan

Normal Clinical follow up

Positive Connue LMWH

Abnormal CTPA

Non-diagnostic Pulmonary angiogram/ serial compression ultrasonography/ MRI

Fig. 1 – Diagnostic algorithm for suspected pulmonary embolism in pregnancy. Adapted from Marik and Plante37 and Arya38. LMWH ¼ low-molecular-weight heparin; CTPA ¼ computerized tomography pulmonary angiography; V/Q ventilation/ perfusion; MRI ¼ magnetic resonance imaging. thrombolytic agent.6,37 Several randomized studies in the nonpregnant population have shown that thrombolysis is more effective than heparin in reducing the clot burden and improving hemodynamics. There does not appear to be any long-term survival benefit,54,55 but in the short term its use may be lifesaving.37 Problems reported due to treatment include maternal bleeding complications in 2.9% at catheter and puncture sites, with no intracranial bleeds reported.55 Fetal deaths were reported in 1.9%, but none were due to abruption.55 If thrombolysis is deemed unsuitable or the mother is moribund, thoracotomy with embolectomy could be discussed with the cardiothoracic surgeons, if this service is available locally. Massive pulmonary embolus causes sufficient obstruction in flow to result in severe hemodynamic instability, right ventricular failure, and hypoxemia. In this unstable situation, extracorporeal membrane oxygenation (ECMO) has been gaining a place in the stabilization of these patients prior to embolectomy.56 With advances in ECMO technology increasing the speed of onset of therapy, they have been reported as an alternative treatment to embolectomy, restoring hemodynamic instability and oxygenation and allowing anticoagulant therapy to work.57 ECMO has been reported for postpartum management of pulmonary embolus58 and experience of ECMO in pregnancy in other settings is increasing worldwide.59,60 Late in pregnancy, if a patient presents with a DVT or a PE, placement of a vena caval filter should be considered once the diagnosis has been confirmed and treatment with UFH should be commenced.8,61 No gestational age cutoff is

recommended but experts suggest that it should be considered when delivery is no more than two weeks away.38 This may reduce the risk of a recurrent PE. However, experience with these devices in pregnancy is limited.62

5. Anticoagulant therapy during labor and delivery Management of anticoagulation therapy at the end of pregnancy poses a challenge as the onset of labor is not predictable, vaginal delivery and cesarean delivery are associated with blood loss and the use of neuraxial anesthesia can be associated with risk. Because of these factors, some obstetricians are reluctant to treat women with LMWH throughout pregnancy and change to UFH for the last few weeks of pregnancy. This approach requires meticulous monitoring of activated partial thromboplastin time (APTT).7 However, the pharmacokinetics of UFH are quite similar to LMWH and due to safety concerns regarding the use of UFH, this management strategy has limited benefit.63,64 Cesarean delivery should not be performed while the patient is fully anticoagulated as it can lead to uncontrolled bleeding and maternal death. If spontaneous labor occurs in a woman receiving therapeutic doses of subcutaneous UFH with a markedly prolonged APTT, protamine sulfate may be required to reduce the risk of bleeding. Women who are taking LMWH should be advised to not inject any further LMWH if she thinks she may be in

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established labor. Guidelines of the American Society of regional Anesthesia and Pain Medicine suggest that spinal anesthesia may be performed 24 h after the last dose of therapeutic LMWH.65 Intravenous UFH should be stopped 6 h before placement and the patient should have a normal APTT. For delivery by elective cesarean, the treatment dose should be held for 24 h prior to surgery. Treatment with LMWH may be resumed within 12 h after vaginal delivery in the absence of persistent bleeding, 12 h after removal of the epidural catheter, or 24 h following neuraxial anesthesia.65,66 There is a 2% risk of wound hematoma following cesarean with both UFH and LMWH.7

6.

Postpartum management of anticoagulation

Women who have experienced a PE outside of pregnancy should be treated for a minimum of 3 months or up to six months when the cause of the event was undetermined.6,8 Due to continuing risk factors and the safety of LMWH, guidelines recommend treatment for the duration of the pregnancy and at least 6 weeks postpartum, for a total of at least 3–6 months.6–8 Neither heparin nor warfarin is contraindicated in breastfeeding. Heparin is not orally active and no problems would be anticipated in the neonate, which is borne out by published reports.6 Warfarin administration should be delayed for at least 3 days following delivery or longer if the risk of postpartum hemorrhage remains high. Heparin treatment should be continued until the warfarin dose is stable for more than 2 days. If LMWH is continued for the duration of the postpartum treatment, the antenatal dosage can be continued or the non-pregnant manufacturers recommendations can be instituted. Patients should be counseled about acceptable forms of contraception during this time. Thrombophilia testing is not recommended while they are on treatment, but should be performed subsequently. Patients should be counseled regarding the need for thromboprophylaxis in other high-risk situations and for future pregnancies, where prophylactic anticoagulation is recommended.

7.

Conclusion

Better recognition of at-risk women and widespread, targeted thromboprophylaxis is key in reducing morbidity and mortality related to pulmonary embolism. This is supported by a statistically significant decrease in VTE-related deaths related to vaginal deliveries3 in the UK following publication of RCOG guidelines in 2004. Careful risk assessment of all women should take place as early as possible in pregnancy and continuing reassessment of risk during and after pregnancy should be ongoing. Despite the increased risk, most women will not require anticoagulation during pregnancy. In those who do require treatment, LMWH has replaced UFH as the treatment of choice for PE in most situations. Careful planning of delivery must be carried out to minimize the risk of bleeding and thrombosis and communication of these risks to the patient and all caregivers is important. Guidelines are effective only when there is a widespread awareness of the

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risks for VTE and reduction in risk and morbidity can only occur with careful application of the recommended advice.

8.

Disclosure

The authors report no proprietary or commercial interest in any product or concept discussed in this article.

refere nces

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