This editorial accompanies publication of “The National Partnership for Maternal Safety (NPMS): Consensus Bundle on Venous Thromboembolism” in Anesthesia & Analgesia. This bundle advocates for expanded risk-based assessment of obstetric patients with more frequent use of pharmacologic prophylaxis based on evidence of decreased maternal mortality with this approach in the United Kingdom. The study outlining the bundle is being copublished in Anesthesia & Analgesia and Obstetrics and Gynecology because leadership from, communication with, and cooperation of obstetric anesthesiologists will be critical if women are to receive high-quality and appropriate thromboprophylaxis and anesthetic care. Given that a larger proportion of women will be receiving pharmacologic prophylaxis both postpartum and during antepartum hospitalizations, obstetric anesthesiologists will play a leading role in designing institution-specific protocols and practices on a hospital-by-hospital basis. This editorial (1) reviews epidemiology of obstetric venous thromboembolism (VTE); (2) reviews leading guidelines including the new bundle recommendations; and (3) highlights the critical role of physician anesthesiologists in leading bundle implementation and ensuring thromboprophylaxis safety.
BACKGROUND AND EPIDEMIOLOGY
VTE is a perennially leading cause of severe obstetric morbidity and mortality in the United States.1,2 Reported estimates of risk are fairly consistent with approximately 1 to 2 cases of pulmonary embolism or deep vein thrombosis occurring per thousand pregnancies3–6 with the highest risk in the immediate postpartum period.7 Among survivors, the sequelae of VTE events include lung damage, cardiovascular changes, and postthrombotic syndrome including pain, edema, and ulcerations. Not all women survive. Mortality estimates from obstetric VTE in the United Kingdom and the United States range from 1 to 2 deaths per 100,000 pregnancies based on national surveillance systems.2,8 Data from the Centers for Disease Control and Prevention and Prevention Pregnancy Mortality Surveillance System found that thrombotic pulmonary embolism was responsible for 313 (9.3%) of 3358 maternal deaths from 2006 to 2010.2 Although cause-specific mortality rates for hemorrhage and hypertensive diseases of pregnancy have declined, the cause-specific mortality ratio for VTE has increased 50% since the Centers for Disease Control and Prevention first started reporting these metrics in 1987.2,9
Although obstetric thromboembolism poses a substantial burden on a population basis, prevention is challenging given that risk is broadly distributed across the millions of women who become pregnant each year and that the time period of elevated risk (ie, pregnancy and the postpartum period together) lasts more than 10 months. This diffusion in risk contrasts with other areas of medicine such as orthopedic surgery, in which patients are at particularly high risk over short time periods. Consequently, the evidence base to support guidelines for optimal thromboprophylaxis strategies has been substantially more difficult to construct.
In an attempt to reduce the incidence of maternal VTE in the United States, both the American College of Obstetricians and Gynecologists (ACOG) and the American Congress of Chest Physicians (ACCP) have released guidelines, which focus primarily on the following: (1) pharmacologic prophylaxis for women with prior VTE events or thrombophilias; and (2) perioperative mechanical prophylaxis for cesarean delivery.10–13 Despite widespread implementation of these guidelines, the maternal burden of obstetric thromboembolism in the United States continues to increase. Population-based administrative data have shown large increases in antepartum and postpartum admissions for women diagnosed with VTE.1,14 Further analysis correlates the increases in hospitalization for VTE with increasing population prevalence of risk factors such as diabetes, heart disease, hypertension, obesity, blood transfusion, hemorrhage, preeclampsia, and postpartum infection.1,14 Both the ACCP and ACOG make limited recommendations regarding risk factor-based prophylaxis apart from prior VTE events, thrombophilias, and cesarean delivery. Obesity, in particular, may be a critically important risk factor; maternal death reviews from the United Kingdom implicated obesity in half of thromboembolism deaths from 2003 to 2008.8
In contrast to US guidelines, recommendations in the United Kingdom from the Royal College of Obstetricians and Gynaecologists (RCOG) support broad, risk factor-based prophylaxis. RCOG’s algorithm recommends prophylaxis with low-molecular-weight heparin (LMWH) for antepartum hospitalizations, mostly patients who have undergone cesarean delivery, and a significant minority of women who have undergone vaginal birth based on risk factors such as obesity, parity ≥3, hemorrhage, infection, preeclampsia, advanced maternal age, medical conditions such as kidney disease, and other factors. The newest guidelines from 2015 recommend outpatient antepartum pharmacologic prophylaxis for patients with multiple risk factors apart from prior thromboembolism and thrombophilia.15 Since comprehensive, prescriptive, risk factor-based guidelines were first released in the United Kingdom in 2004, maternal risk from VTE decreased substantially from 1.94 deaths per 100,000 births between 2003 and 2005 to 0.79 deaths per 100,000 births between 2006 and 2008.8 The most recent death rate of 1.01 (2011–2013) is lower than any of the 7 triennial periods from 1985 to 2005.16
PROPHYLAXIS STRATEGIES AND GUIDELINE RECOMMENDATIONS
In creating the VTE bundle, the NPMS VTE working group reviewed guidelines from the ACOG, ACCP, and RCOG. These guideline recommendations and the core recommendations from the NPMS VTE bundle are outlined subsequently. A detailed review of ACOG, ACCP, and RCOG guidelines and NPMS recommendations are available in the bundle study. In short, RCOG recommends pharmacologic prophylaxis for the largest proportion of patients, ACCP has intermediate recommendations, and ACOG supports pharmacologic prophylaxis for the smallest proportion of women. The core concept underlying the NPMS recommendations is that the current burden sustained by obstetric patients from VTE in the United States is unacceptable and that to improve outcomes, VTE risk assessment should occur throughout pregnancy with use of pharmacologic prophylaxis as appropriate.
Outpatient Antepartum Prophylaxis
Both the ACOG and ACCP support outpatient pharmacologic prophylaxis of the highest risk patients such as those with prior VTE events and with thrombophilias. The NPMS VTE bundle supports this approach with use of LMWH and unfractionated heparin (UFH) for patients based primarily on ACCP/ACOG criteria. In comparison, new recommendations from the RCOG specify outpatient antepartum prophylaxis based on risk factors for a larger proportion of patients beyond those with thrombophilias and prior VTE events.15
Antepartum Hospital Admissions
ACCP and ACOG guidelines can be interpreted to support pharmacologic prophylaxis with UFH or LMWH for antepartum admissions for the highest risk patients. In contrast, the RCOG supports use of pharmacologic prophylaxis for the majority of antepartum admissions in the absence of contraindications. Given the substantial increase in risk posed by inpatient bedrest, the NMPS VTE bundle aligns with RCOG and supports pharmacologic prophylaxis with LMWH or twice-daily UFH for all patients hospitalized at least 72 hours who are not at high risk for bleeding or imminent delivery.
Inpatient Cesarean Delivery Thromboprophylaxis
For cesarean delivery, the ACOG and ACCP support mechanical thromboprophylaxis with pneumatic compression devices.11,13 The ACCP specifies that prophylaxis with UFH/LMWH be utilized for a more limited set of indications,12 whereas the ACOG specifies pharmacologic prophylaxis for patients with prior VTE and thrombophilias. In comparison, the RCOG supports pharmacologic prophylaxis postcesarean for a range of relatively common risk factors including advanced maternal age, cesarean delivery in labor, obesity, parity ≥3, maternal age >35 years, hemorrhage more than 1 L, preeclampsia, and multiple gestation.15 To illustrate the practical implications of these varying guidelines, we reviewed a cohort of postcesarean patients at our medical center and found that 1%, 35%, and 85% of patients would receive pharmacologic prophylaxis under ACOG, ACCP, and RCOG criteria, respectively.17
With regard to postcesarean pharmacologic prophylaxis, the NPMS bundle supports two approaches: (1) offering empiric LMWH/UFH to all patients postcesarean on an opt-out basis; or (2) a risk factor-based approach. The NPMS bundle does not specify which risk factors should be used and acceptable options include RCOG criteria, ACCP criteria, or a version of the Caprini scoring system modified for obstetric patients that is presented in the bundle.
Inpatient Vaginal Delivery Thromboprophylaxis
The NMPS bundle supports prophylaxis recommendations from ACOG and ACCP for women hospitalized after a vaginal delivery. Patients who should receive prophylaxis primarily include those with thrombophilias, immobilization, prior events, and positive family histories.10–12 This approach differs from RCOG guidelines that support risk factor-based prophylaxis.
Outpatient Postpartum Thromboprophylaxis
The NMPS bundle supports extended pharmacologic prophylaxis on discharge from a delivery hospitalization based on ACOG and ACCP recommendations. Providing extended pharmacologic prophylaxis for 6 weeks postpartum to women with prior events and thrombophilias also aligns with RCOG recommendations.
The NPMS VTE bundle specifies that for inpatients receiving pharmacologic prophylaxis, the recommended dose and agent is 5000 U twice-daily UFH. For antepartum outpatients approaching term, the decision to use 5000 U twice daily versus the higher doses often recommended during late gestation should be based on consideration of the risks and benefits of a higher dose taking into account potential restrictions on neuraxial anesthesia whether urgent or emergent delivery is required. At the time of publication, preliminary new recommendations from the American Society for Regional Anesthesia and Pain Medicinea suggest that neuraxial procedures be delayed “4 hours (and ideally 6 hours)” after a 5000-U dose of subcutaneous UFH. Although it is unclear how these recommendations from American Society for Regional Anesthesia and Pain Medicine may change practice, well-coordinated management between obstetricians and obstetric anesthesiologists will be of increasing clinical importance. The Society for Obstetric Anesthesia and Perinatology is concurrently preparing an expert statement that includes guidance on neuraxial anesthesia in relation to pharmacologic prophylaxis recommendations to facilitate care coordination and delivery planning.
ROLE OF OBSTETRIC ANESTHESIOLOGISTS
Obstetric anesthesiologists will play a critical role in providing safe, effective VTE prophylaxis both through hospital-level implementation leadership and through sound decision-making and care planning for individual patients. For hospitalized antepartum patients who may require emergency delivery anesthesia, the benefits of VTE risk reduction from pharmacologic compared with mechanical prophylaxis may be outweighed by risks from unplanned general anesthesia or complications such as spinal hematoma. Active involvement in counseling and planning on the part of obstetric anesthesiologists will be critical for patients and families to receive full disclosure of competing risks and be able to participate in shared decision-making.
In considering implementation, both resources and patient populations served vary significantly by institution. On a hospital-by-hospital basis, anesthesiology leadership will be required to determine how to best provide care that optimizes both VTE pharmacologic prophylaxis and the likelihood of safe neuraxial blockade, even for high-risk patients, while ensuring that those carefully constructed care plans can be carried forward by anesthesiologists covering out of hours and appropriately adapted as clinical circumstances change. The degree to which care can be directed by universal protocols and systems will depend on a combination of patient, hospital, and obstetric anesthesia provider factors. For complicated, high-risk patients, low-risk delivery centers can consider transfer or referral to a tertiary center with a system of regionalized maternal care. Although centers may vary in their use of risk factor criteria, prophylaxis regimens, and protocols, we believe that clear, prescriptive management recommendations from obstetric anesthesiologists are the only means by which patients can receive safe, standardized, high-quality care.
VTE will continue to be a leading cause of maternal mortality unless prophylaxis is expanded to a larger proportion of patients given the increased population-based risk for events. Guidelines from the RCOG, which support risk-factor-based prophylaxis, have been associated with decreased maternal risk, and the VTE bundle from the NPMS supports broader prophylaxis strategies than major US guidelines from the ACCP and ACOG. Optimizing prophylaxis strategies will require obstetric anesthesiologists to play a critical leadership role both on a hospital level in terms of formulating safe guidelines and practices and in terms of creating individualized care plans.
Name: Alexander M. Friedman, MD.
Contribution: This author helped write the manuscript.
Name: Richard M. Smiley, MD, PhD.
Contribution: This author helped write the manuscript.
This manuscript was handled by: Jill Mhyre, MD.
a The ASRA coagulation “app,” available at https://itunes.apple.com/us/app/asra-coags/id858796572?mt=8. Accessed June 30, 2016.
1. Callaghan WM, Creanga AA, Kuklina EV. Severe maternal morbidity among delivery and postpartum hospitalizations in the United States. Obstet Gynecol. 2012;120:1029–1036.
2. Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM. Pregnancy-related mortality in the United States, 2006-2010. Obstet Gynecol. 2015;125:5–12.
3. Simpson EL, Lawrenson RA, Nightingale AL, Farmer RD. Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. BJOG. 2001;108:56–60.
4. Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ 3rd. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med. 2005;143:697–706.
5. McColl MD, Ramsay JE, Tait RC, et al. Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost. 1997;78:1183–1188.
6. James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol. 2006;194:1311–1315.
7. Sultan AA, West J, Tata LJ, Fleming KM, Nelson-Piercy C, Grainge MJ. Risk of first venous thromboembolism in and around pregnancy: a population-based cohort study. Br J Haematol. 2012;156:366–373.
8. Cantwell R, Clutton-Brock T, Cooper G, et al. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The eighth report of the confidential enquiries into maternal deaths in the United Kingdom. BJOG. 2011;118 (Suppl 1):1–203.
9. Berg CJ, Callaghan WM, Syverson C, Henderson Z. Pregnancy-related mortality in the United States, 1998 to 2005. Obstet Gynecol. 2010;116:1302–1309.
10. American College of O, Gynecologists Women’s Health Care P. ACOG Practice Bulletin No. 138: Inherited thrombophilias in pregnancy. Obstet Gynecol. 2013;122:706–717.
11. James A. Committee on practice bulletins—obstetrics. Practice bulletin no. 123: thromboembolism in pregnancy. Obstet Gynecol. 2011;118:718–729.
12. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e691S–e736S.
13. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e227S–e77S.
14. Ghaji N, Boulet SL, Tepper N, Hooper WC. Trends in venous thromboembolism among pregnancy-related hospitalizations, United States, 1994-2009. Am J Obstet Gynecol. 2013;209:433.e1–8.
15. The Royal College of Obstetricians and Gynaecologists. Thrombosis and Embolism During Pregnancy and the Puerperium, Reducing the Risk. London, UK: The Royal College of Obstetricians and Gynaecologists. Green-Top Guideline No. 37a. 2015.
16. Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006;367:1066–1074.
17. Palmerola KL, D’Alton ME, Brock CO, Friedman AM. A comparison of recommendations for pharmacologic thromboembolism prophylaxis after caesarean delivery from three major guidelines. BJOG. 2015;[epub ahead of print].