Strategies for the prevention of maternal death from venous thromboembolism clinical recommendations based on current literature

Risk assessment

The first step is early recognition and comprehensive assessment of the individual risk factors for VTE at the first prenatal visit including the patient’s family and personal history and a careful physical examination (e.g. saphenous varicosis).

Women with previous VTE should be offered pre-pregnancy counselling and a prospective management plan for thromboprophylaxis in pregnancy made [20].

It is prudent to use a standardized check list of VTE risk factors readily available in every maternal unit, since it is challenging for the obstetrician in daily practice to keep all risk factors in mind [21].

The RCOG Guidelines No. 37a [22] include adjusted odds ratio estimates for common obstetric VTE risk factors based on literature review.

Standardized risk assessment should be repeated at any antepartum hospital admission, before and immediately after delivery and at the patient’s discharge from hospital, since the risk profile may change significantly in the course of pregnancy and the early postpartum period [12, 22]. Thus, women at increased risk of VTE can be identified timely and prophylaxis be adapted adequately.

Risk stratification

Appropriate risk stratification to decide who might benefit from pharmacological thromboprophylaxis is mandatory.

Risk stratification remains a matter of debate, since guideline recommendations vary considerably.

Nevertheless, VTE risk assessment tools for pregnant and postpartum women should be consistent with national guidance [6].

The RCOG Guidelines No. 37a [22] recommend a scoring system weighing different risk factors (1–4 points) for VTE, while other guidelines propose pharmacological thromboprophylaxis, if the risk threshold resulting from 1 or ≥2 minor risk factors exceeds 3% [23] and 1% [24], respectively. It is mandatory to implement one of these risk stratification tools to the protocol of every maternity unit [21].

However, there is clear evidence that doctors and midwives find existing risk scoring systems difficult to apply consistently in practice.

There is a need for development of a tool to make the current risk assessment systems simpler and more reproducible [9].

Risk-based thromboprophylaxis

The cornerstone in preventing VTE-related maternal deaths is a risk-based mechanical and pharmacological thromboprophylaxis antenatally and particularly in the postpartum period with the highest daily risk of VTE.

It should be ensured that women on prophylactic and treatment dose anticoagulation have a structured management plan to guide practitioners during the antenatal, intrapartum and postnatal period [6].

The following aspects should be considered

1. Keep in mind that strict antepartum immobilization for at least a week in women with an elevated body mass index at the first prenatal visit is associated with a 62-fold risk for antepartum VTE and a 40-fold risk for postpartum VTE [25].

2. Start antenatal pharmacological prophylaxis in high-risk patients (e.g. RCOG Scoring ≥4) as early in pregnancy as practicable, since more than 20% of PE occur already in the first trimester [22].

3. Consider body-weight adjusted dosage for prophylaxis and treatment when using low-molecular-weight heparin (LMWH) antenatally and in the postpartum period [22].

4. The recent key message from the UK Confidential Enquiries recommends reweighing women at 28 weeks and postpartum to more accurately determine their VTE risk score and the appropriate prophylactic dose of LMWH [6].

5. Adjust the LMWH dosage and the duration of prophylaxis to the individual patient’s risk for VTE, as recommended by guidelines [26]. Women at (very) high VTE risk (e.g. previous unprovoked VTE, high-risk thrombophilia) need intermediate or therapeutic dosages of LMWH from the beginning of pregnancy until 6 weeks postpartum or even longer [22].

6. Take into account that some VTE risk factors (e.g. heart disease, thrombophilia, saphenous varicosis) may by associated with an increased risk for VTE even beyond 42 days after the end of pregnancy [27]. It has been shown that there is a two-fold increase in the risk of VTE from 7 to 12 weeks postpartum compared with the same time period a year later [28].

Timing of pharmacological thromboprophylaxis

Concerning timing of pharmacological thromboprophylaxis the following aspects should be taken into account:

1. Minimize the time interval without LMWH prophylaxis while awaiting and undergoing induction of labour. In women at high risk LMWH should not be withheld until labour is established and discussion regarding the necessary 12 h window prior to regional anaesthesia should be individualized [6].

2. If there are no contraindications, start LMWH 4–6 h after vaginal delivery and 6–12 h after cesarean section [22, 29], taking into consideration current guidelines for regional anaesthesia [30].

Post-cesarean thromboprophylaxis

The absolute risk of VTE has been estimated 2.6 to 4.3/100.000 cesarean sections [31].

Guideline recommendations differ significantly to whether women should receive post-cesarean heparin prophylaxis while hospitalized, which may lead to large differences in clinical practice [32].

Comparing guidelines, 1% of patients would receive heparin prophylaxis based on American College of Obstetricians and Gynecologists (ACOG) criteria. 35% based on American College of Clinical Pharmacy (ACCP) criteria and 85% based on Royal College of Obstetricians and Gynecologists (RCOG) criteria [16].

A further problem is that there is insufficient evidence on the benefit of post-cesarean LMWH prophylaxis from randomized, controlled trials [33].

Considering the great variety of VTE risk factors, the immanent risk not recognizing all risk factors timely and the low incidence of significant LMWH side effects we and others advocate universal heparin (LMWH) prophylaxis rather than a selective [12, 15, 34]. The National Partnership for Maternal Safety is compatible with the RCOG recommendations [22], supporting heparin prophylaxis for most post-cesarean patients based on scoring, and additionally propose empiric post-cesarean heparin prophylaxis withheld on an opt-out basis [12]. The arguments for broader use of heparin prophylaxis have recently been highlighted by Friedman and D’Alton [15].

According to a nation-wide survey, 93% of the German obstetricians prefer universal post-cesarean LMWH prophylaxis [35].

It has to be acknowledged that universal LMWH prophylaxis is associated with significantly higher costs, which may be a limiting factor in low-resource settings.

Mechanical thromboprophylaxis

Although the benefits of graduated compression stockings and pneumatic compression devices have never been validated by randomized controlled trials in obstetric populations, a policy of universal thromboprophylaxis using pneumatic compression devices during and after cesarean delivery has shown to reduce maternal deaths from post-cesarean thromboembolism by 86% [36], which is in line with the reported efficacy for other types of abdominal-pelvic surgery.

ACOG recommends universal perioperative use of pneumatic compression devices for all women not already receiving pharmacological thromboprophylaxis [29].

However, poor device compliance is a major problem with mechanical prophylaxis outside the immediate perioperative setting [32].

In a German-wide survey only 66% of the obstetric units routinely used graduated compression stockings during and after cesarean delivery [35].

Mechanical prophylaxis should be provided to patients with contraindications for heparin prophylaxis [23, 29].

Early mobilization and avoidance of dehydration in the early postpartum period may also contribute to a reduction of VTE events, however, the evidence for these measures is insufficient.

Postnatal thromboprophylaxis

In the light of steadily decreasing length of hospital stay after vaginal and cesarean deliveries, it can be assumed, that the majority of VTE today occur after patient’s discharge from hospital.

Therefore, it is urgently necessary to avoid gaps in the postpartum prescription of LMWH, when the patient is at home [21].

The hospital should timely inform the physician (obstetrician) in practice on the individual patient’s risk for postpartum VTE after her discharge from hospital and should provide a management plan for postpartum heparin prophylaxis. It should be ensured that the patient receives a full postnatal course of LMWH [8].

Good communication between hospital and community midwifery staff is also required, since midwives can check that the patient is actually administering the injections, understands the indication and is reminded of the red flags for VTE [6].

Early recognition of pulmonary embolism

Obstetricians and midwives should be aware that acute chest pain, sudden breathlessness and episodes of collapse/loss of consciousness can be symptoms of PE even in the absence of signs of DVT [37].

VTE can develop despite the use of thromboprophylaxis or treatment doses of heparin, so patients taking heparin who present with clinical features suggestive of a PE should be immediately investigated [8].

Any patient with symptoms and/or signs suggestive of PE should receive intravenous unfractionated heparin (e.g. 80 IE/kg as a bolus, followed by 18 IE/kg continuously) immediately until the diagnosis is excluded by objective testing, unless treatment is strongly contraindicated [20].

Of note, PE may be fatal in almost 15% of patients, and 66% of these deaths will occur within 30 min after the embolic event [20].

All hospitals should have a protocol for the diagnosis and management of suspected VTE in pregnancy and the puerperium, which may require multidisciplinary team involvement [20].

Audits

Every maternal unit should review all thromboembolism events carefully for system issues and compliance with protocols [12].

To learn from failures and realize, if and where improvement is needed are further crucial points to prevent VTE-related maternal deaths [21].

Universal maternal audit instruments may help to assign cause of death in maternal deaths review process [38].