Rates of transfusion during childbirth have increased in resource-rich countries.1 In the United States, the rate of severe postpartum hemorrhage (PPH) requiring transfusion increased from 30.4 to 96.4 per 10,000 delivery hospitalizations for the time periods between 1998 and 1999 to 2008 and 2009, respectively.2 Thus, there is an onus for anesthesiologists to familiarize themselves with current recommendations in Patient Blood Management (PBM) in the setting of PPH.
As defined by the Institute of Medicine, clinical guidelines are “systemically developed statements to assist providers and patient decisions about appropriate health care for specific clinical circumstances.”3 By providing a clear description and appraisal of scientific evidence, guidelines can enhance clinician and patient decision making. In recent years, there has been a surge in clinical practice guidelines, many giving inconsistent or opposing recommendations,4 which may negatively impact clinical care delivery.5 This is relevant to clinicians in the United States because government health care programs increasingly rely on guidelines to develop performance measures and quality metrics.6 In obstetrics, the presence of conflicting PBM guidelines may lead to important variations in clinical practice. For example, recommendations for fibrinogen supplementation differ across subspecialty societies. The European Society of Anaesthesiology recommends fibrinogen supplementation when fibrinogen levels are <200 mg/dL (in the setting of severe perioperative bleeding),7 whereas several obstetric societies recommend treatment for fibrinogen levels <100 mg/dL.8,9 Side-by-side comparison of PBM recommendations made by national obstetric societies would allow clinicians to assess the strengths and limitations of existing guidelines.
Guidelines for PPH management have been published by a number of obstetric societies, including the American College of Obstetricians and Gynecologists (ACOG); the Royal College of Obstetricians and Gynecologists (RCOG), United Kingdom; the Royal Australian and New Zealand College of Obstetricians and Gynecologists (RANZCOG); the Society of Obstetricians and Gynecologists of Canada (SOGC); and the French College of Gynaecologists and Obstetricians (CNGOF) in collaboration with the French Society of Anesthesiology and Intensive Care. In a recent review, Dahlke et al10 compared each society’s recommendations for PPH prevention and treatment, including uterotonic agents, interventional radiology procedures, and surgical interventions. However, in this review, PBM recommendations were not examined in detail.
In recent years, PBM has been developed as an evolving evidence-based approach with a number of key goals: (i) to identify, evaluate, and manage anemia; (ii) reduce iatrogenic blood loss; (iii) optimize hemostasis; and (iv) establish decision thresholds for transfusion.11 All these aspects of PBM are applicable to PPH prevention and management. Other strategies that may be applicable to PPH management include fixed ratios of plasma-to-red blood cells,12 massive transfusion and hemorrhage protocols,13,14 and pharmacological therapies such as prothrombotic and antifibrinolytic agents.15
The primary aims of this qualitative review were to assess PPH guidelines published by national obstetric societies, with a focus on recommendations for transfusion and PBM. Guidelines published by national anesthesiology, hematology, and transfusion societies were secondarily reviewed to assess transfusion and PBM recommendations applicable to obstetrics.
We conducted our appraisal between April 1, 2015, and April 30, 2016. During this interval, we reviewed the most recent PPH guidelines published by the following national obstetric societies (RCOG,8 SOGC,16 ACOG,17 RANZCOG,9 and CNGOF18), an interdisciplinary group of experts from Austria, Germany, and Switzerland (D-A-CH),19 and an international expert panel convened to develop consensus recommendations for PPH management (hereafter referred to as expert panel).20 The goal of D-A-CH was to develop a PPH algorithm by reviewing guidelines from national societies in Austria, Germany, Switzerland, and other international PPH algorithms. For each society, we searched Web sites to identify the most recently published guidelines. To confirm that we identified the most recent guidelines, we searched The National Guideline Clearinghouse (the Agency for Healthcare Research and Quality, US Government), MEDLINE, EMBASE, Ovid, Google Scholar, and Google. Last, we reviewed transfusion and PBM recommendations in the PPH bundle published by the National Partnership for Maternal Safety (NPMS) in 2015.*,21
Our review is intended to target anesthesia and obstetric providers from well-resourced countries. Therefore, we did not review PPH guidelines by the World Health Organization22 and the International Federation of Gynecology and Obstetrics,23 which are more clinically relevant to providers in low-resource settings. Four authors (R.S., C.F.W., N.A., A.J.B.) reviewed each English language document independently using a data extraction form, and discrepancies were resolved by consensus. A.T. reviewed D-A-CH guidelines.
For each set of guidelines, we evaluated the following background information: year of publication, information about the members of each guideline committee, definitions for PPH, and the information sources used by each society for developing their guidelines.
We reviewed specific aspects of each society’s blood transfusion recommendations, including the indications for transfusion with red blood cells (RBCs), plasma, platelets (PLTs), and cryoprecipitate; and recommendations for fixed transfusion ratios and/or goal-directed transfusion therapy. We focused our review on the following key aspects of PBM: (i) transfusion therapy; (ii) pharmacological agents, such as recombinant factor VIIa (rFVIIa), tranexamic acid, fibrinogen concentrate; and (iii) other interventions, such as cell salvage. We also examined whether other approaches were recommended, such as autologous transfusion, coagulation monitoring using laboratory tests and point-of-care devices, such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM).
We also evaluated whether obstetric-specific blood transfusion recommendations are described in PBM guidelines published since 2010 by nationally or internationally recognized anesthesia societies and blood bank organizations, including the AABB (formerly the American Association of Blood Banks),24–26 American Society of Anesthesiologists (ASA),27 European Society of Anaesthesiology (ESA),7 British Committee for Standards in Haematology (BSCH),28 National Blood Authority (NBA) of Australia,29 and the Association of Anaesthetists of Great Britain and Ireland (AAGBI).30
Background information for these PPH guidelines is presented in Table 1. We observed a wide range for the year of publication (2006 to 2016). For each society, an interdisciplinary committee developed the PPH guideline; yet, no specific criteria were described for selecting committee members. The ACOG did not provide details of their committee members’ area of expertise. The other societies encompassed committee members from a number of disciplines, including obstetrics, gynecology, hematology, transfusion medicine, anesthesiology, family medicine, neonatology, nursing, and midwifery. Lay people were included on several committees, specifically a representative from the Jehovah’s Witness Organization (RCOG) and a patient representative (RANZCOG). The RCOG, D-A-CH, CNGOF, and the expert panel provided details of each committee member’s base institution and specialty.
The societies used different approaches to examine the literature. Five societies (ACOG, SOGC, RCOG, CNGOF, and the expert panel) provided details about the sources of information used to formulate their guidelines. In contrast, the RANZCOG, D-A-CH, and NPMS provided relatively limited information. The levels of evidence were graded differently by each society. The ACOG and the expert panel used the grading system method outlined by the US Preventative Services Task Force,† the SOGC used the Evaluation of Evidence criteria from the Canadian Task Force on Preventative Health Care,31 the RCOG used an internal grading system, the RANZCOG used a grading system endorsed by the Australian National Health and Medical Research Council,‡ and the CNGOF used a framework defined by the French Health Authority.§ Although the NPMS provided a resource listing for the bundle, no information was provided about how the quality of evidence was evaluated or how the strength of their recommendations was determined.
All societies used blood loss as a key determinant for classifying PPH (Table 1). Only the ACOG classified PPH according to mode of delivery: >500 mL for vaginal delivery versus >1000 mL for cesarean delivery.
Key aspects of the national obstetric societies’ transfusion recommendations are presented in Table 2. There were limited descriptions for blood ordering strategies by all societies. The RCOG and ACOG recommended preemptive ordering of blood products only for patients with suspected placenta accreta/percreta. The D-A-CH and RCOG recommended cross-matching and ordering blood as soon as PPH is recognized. Most societies based their indications for transfusion on the degree of blood loss. Target hematological indices were described by the RCOG, RANZCOG, CNGOF, and D-A-CH. For guiding resuscitation, the RANZCOG and D-A-CH described other physiologic indices, such as a pH >7.2. However, the frequency of laboratory testing was poorly described, with only the expert panel recommending testing of coagulation parameters every 45 to 60 minutes.
Broad consensus for plasma use was lacking. The RCOG and RANZCOG recommended fresh frozen plasma (FFP) in the setting of a prolonged prothrombin time (PT), or activated partial thromboplastin time (APTT). The D-A-CH stated that FFP should be considered for correcting a coagulation disorder. The CNGOF indicated that FFP can be administered without waiting for laboratory results, depending on hemorrhage severity. The majority of the societies did not describe fixed-ratio transfusion approaches, such as 1:1 of RBC:FFP. Only the RCOG suggested transfusing 4 units of FFP for every 6 units RBC.
Societies’ recommendations for PLT transfusion were similar. In the setting of PPH, the RCOG, RANZCOG, CNGOF, and D-A-CH recommended PLT transfusion if the PLT count is <50 × 109/L. Recommendations for fibrinogen supplementation (with cryoprecipitate or fibrinogen concentrate) were less consistent. Two societies (RCOG, and RANZCOG) recommended supplementation for a fibrinogen concentration <100 mg/dL. A higher threshold (200 mg/dL) was recommended by the expert panel and the CNGOF.
Three societies—the RANZCOG, NPMS, and the expert panel—made reference to a massive transfusion protocol (MTP). The RANZCOG guidelines contained an MTP algorithm, with criteria for activating the MTP (actual or anticipated transfusion of 4 units RBC in <4 hours). No society provided indications for discontinuing or deactivating an MTP.
Recommendations for using pharmacologic agents are presented in Table 2. Among the societies, there was no consensus for administering rFVIIa. The RCOG, RANZCOG, D-A-CH, CNGOF, and the expert panel recommended rFVIIa for treating life-threatening or uncontrolled hemorrhage. Neither the ACOG nor the SOGC recommended rFVIIa. Both societies cite lack of evidence for efficacy; furthermore, ACOG expressed concern for potential thromboembolic events and cost implications.
Recommendations for using antifibrinolytic agents were also inconsistent. The RANZCOG, D-A-CH, and the expert panel recommended tranexamic acid. The CNGOF recommended that the use of tranexamic acid be at the clinician’s discretion, despite stating that its use is not suitable for routine PPH management and that evidence is lacking to support its role. The RCOG recommended against using antifibrinolytics, stating that “there is a consensus view that fibrinolytics seldom, if ever, have a place in” (PPH management). No society recommended using TEG or ROTEM to detect hyperfibrinolysis before administering tranexamic acid. No other antifibrinolytics were discussed by the societies.
We found few recommendations for other PBM strategies in the PPH guidelines, such as point-of-care testing and cell salvage. Only the D-A-CH and the expert panel included recommendations for point-of-care testing with TEG or ROTEM. Only ACOG and the RANZCOG made reference to cell salvage. The ACOG recommended autologous transfusion for women with rare antibodies. Although no society strongly endorsed colloids for volume replacement, the D-A-CH stated that colloids can falsely elevate fibrinogen levels.
Transfusion Recommendations From Other Societies
Table 3 summarizes the main recommendations from guidelines published since 2010 by anesthesiology societies (the ASA, the ESA, and the AAGBI) and transfusion societies (the AABB, the NBA, and BSCH). The aims of each society’s guidelines differed (Table 3). Guidelines were geared to different patient populations: surgical patients (ESA and ASA), stable hospitalized patients (AABB), and patients with hemorrhage (BSCH). The NBA published several modules for PBM.‖ In Table 3, we summarized the NBA recommendations specific to pregnancy and maternity (from module 5). The ESA, BSCH, NBA, and AAGBI guidelines included a specific section for obstetric hemorrhage. Because the AABB PLT guidelines did not include recommendations related to hemorrhage, they are excluded from our review.
Recommendations for transfusing RBC and plasma were inconsistent across the societies (Table 3). For example, both the ESA and the BCSH recommended fixed ratios of RBC:FFP, the BCSH recommended a FFP:RBC ratio of at least 1:2, and the AAGBI recommended fixed ratios only in the face of continued hemorrhage. In contrast, the ASA did not stipulate using fixed ratios. In their module on critical bleeding and massive transfusion,¶ the NBA state that there is insufficient evidence to support or refute the use of specific ratios of RBCs to other blood components.
The use of laboratory indices for guiding PLT transfusion or fibrinogen supplementation was described by most of the societies. For fibrinogen supplementation, the ESA recommended fibrinogen concentrate over cryoprecipitate for treating hypofibrinogenemia.
The AAGBI and NBA suggested tranexamic acid for managing women with severe PPH. The ESA and BSCH recommended tranexamic acid for adult trauma patients and in adult patients with nontraumatic major hemorrhage. However, the ASA was more reserved in their recommendations, highlighting the lack of safety data in obstetrics. The ASA, ESA, and NBA recommended that rFVIIa be considered as a rescue therapy, whereas the BCSH recommended against the use of rFVIIa. None of the AABB guidelines included adjuncts to transfusion management.
In general, guidelines published by the nonobstetric societies (ASA, ESA, AABB, and BSCH) contained more contemporary approaches to transfusion management and PBM compared with those published by obstetric societies. These approaches include an MTP, goal-directed therapy using point-of-care testing, and early treatment of hypofibrinogenemia.11,13,15,32,33 However, the evidence base that supports the use of these approaches in obstetrics is limited. It is likely that consensus of expert opinions fills gaps in areas lacking scientific evidence. To improve the quality of PBM guidelines in obstetrics, prospective clinical studies and cost-effectiveness studies are urgently needed for women with severe PPH.
Among the obstetric societies, reasons for the variation in the transfusion and PBM recommendations are uncertain. It is possible that different dates of publication, methods for guideline development and literature review, and different compositions of guideline review committees may account for some of this variation. Other factors include variation in the willingness of guideline committees to include evidence from the nonobstetric setting, and differences in expert opinion when evidence is lacking. Also, it is unclear whether societies took into account the cost-effectiveness of individual interventions, patient preferences and opinions, and the potential influence of outside agencies with special interests, such as pharmaceutical and device companies. These are important factors to consider when reviewing clinical practice guidelines.4,34 In particular, the involvement of patients and the public, including Jehovah’s witnesses, in clinical practice guideline development has been endorsed by the Institute of Medicine.35 Patient and public involvement is important for a number of reasons: to examine whether special interests are present; to determine whether guidelines can be easily understood by patients; and to provide safeguards against conflict of interests that skew judgment of the guideline committee members.35
In addition to scientific evidence and expert opinions, clinical practice guidelines should account for both the resource implications and the feasibility of the recommended interventions.36 These have important implications for low-volume birth facilities in geographically remote locations that may have limited access to prothrombotic drugs or a sufficient blood bank inventory. It is unrealistic for national societies to account for all types and locations of birth facility, and as highlighted by the NMPS, an emergency hemorrhage action plan should be tailored according to the individual capabilities of each hospital. With data suggesting that hospital-level factors explain a large portion of the variability in transfusion rates in obstetrics,37 more research is needed to determine the most clinically and cost-effective patient blood management approaches according to specific hospital characteristics.
Transfusion Criteria During Active Blood Loss
It is well-recognized that peripartum blood loss is inaccurately measured, with accuracy worsening at larger volumes of blood loss.38–41 Determining whether and how blood loss measurements influence clinical practice is challenging. In a high-quality systematic review of studies that evaluated methods of blood loss assessment, Hancock et al42 concluded that improved accuracy of blood loss measurement does not facilitate earlier recognition of PPH or prevent progression to more severe PPH. In contrast, data from an impact study from a large US health care system suggested that the introduction of a standardized approach to hemorrhage management, including immediate release of blood products from blood bank, may reduce the overall blood product use.43 Despite the challenges faced in accurately quantifying blood loss, the magnitude and rate of blood loss will likely remain an inherent component of clinicians’ transfusion decision-making.
Some of the societies recommended transfusion if unstable vital signs accompany blood loss. However, the strength of the associations between volume of blood loss with maternal heart rate and blood pressure is uncertain. In a systematic review, Pacagnella et al44 observed that heart rate and blood pressure were associated with blood loss in 22 of 24 studies and 17 of 23 studies, respectively. However, values for area under the receiver-operating characteristics curve varied (heart rate = 0.56–0.79 and systolic blood pressure = 0.77–0.84, respectively). In trauma patients with shock, systolic blood pressure has been shown to correlate poorly with base deficit (r = 0.28).45 Although marked heterogeneity may exist in patients’ hemodynamic responses to early severe postpartum bleeding, clinicians will likely continue to account for vital signs when assessing clinical indications for transfusion. A survey of transfusion practice among ASA members provides some support for this assertion; 46% respondents indicated that the decision to transfuse is based on a number of factors: intraoperative hemodynamic status, medical condition of the patient, and age of the patient.46 Technologies, including echocardiography and cardiac ultrasound, can provide more detailed information about patients’ volume status and hemodynamic responses to resuscitation and transfusion. Fuller evaluation of these technologies is needed in the setting of PPH.47,48 Similarly, noninvasive hemoglobin monitors are commercially available, but concerns about accuracy and precision may limit their clinical utility in the obstetric setting.49
Preemptive Blood Ordering
Excluding patients with suspected abnormal placentation, obstetric societies’ guidelines lacked information about preemptive or predelivery blood ordering. The California Maternal Quality Care Collaborative (CMQCC) published a bundle describing care practices for patients with obstetric hemorrhage, with an approach for risk-stratifying patients for PPH and pretransfusion testing.50 The CMQCC assigned patients as low-, medium-, or high-risk category based on the presence/absence of selected risk factors. For each group, recommendations were as follows: no prenatal pretransfusion testing, type and screen testing, or type and cross-match for 2 units RBC, respectively. Two retrospective studies examined the accuracy of CMQCC risk stratification at single US obstetric centers. Wu et al51 reported transfusion rates of 2.1%, 4.5%, and 22.6% among low-, medium-, and high-risk women, respectively. In contrast, Dilla et al52 observed lower rates of transfusion in each group (0.8%, 2%, and 7.3%, respectively). Given that a wide variation in obstetric transfusion rates has previously been reported,37 between-hospital differences in transfusion rates for each at-risk group are not unexpected. Nonetheless, the low transfusion rates reported in each low- and medium-risk group suggest that pretransfusion testing for these women may not be warranted.
In the nonobstetric setting, historical blood utilization data from anesthesia information systems have been used to determine preoperative blood orders for specific surgical procedures, referred to as the maximum surgical blood ordering schedule.53–55 To optimize blood ordering practices in obstetrics, investigations are needed of predelivery maximum blood ordering schedules coupled with blood component utilization relevant to the peripartum and postpartum periods.
Massive Transfusion Protocol
The majority of obstetric guidelines lacked detailed information about the availability of a MTP. Only 3 obstetric societies (RANZCOG, NPMS, and the expert panel) mentioned the use of a MTP, with limited information about the benefits of implementing a MTP. An institutional MTP can be vital for physicians managing severe and ongoing postpartum bleeding.56–58 An MTP provides a structured, systemwide process for the delivery of sufficient types and volumes of blood products, with short turnaround times from ordering to receipt of blood products. In addition, processes for MTP activation and deactivation are standardized. These attributes are important because the Confidential Enquiry into Maternal and Child Health (CEMACH: United Kingdom) have indicated that time delays in receiving blood products may contribute toward severe obstetric morbidity and mortality.59 Futhermore, evidence suggests that rates of massive transfusion in obstetrics are increasing. In a study using administrative data from New York State, Mhyre et al60 reported that the rate of massive transfusion during delivery hospitalizations increased from 6.2 per 10,000 deliveries between 1998 and 2002 to 7.3 per 10,000 deliveries between 2003 and 2007. Although no studies have compared maternal outcomes between those managed with a MTP versus nonprotocol-based transfusion strategies, there have been calls for hospitals to implement a MTP as a key systemwide process for managing severe PPH.14,61 On the basis of a recent survey of directors of US academic obstetric anesthesia units, 93% units have a MTP in place.62 The median number of units of RBC, plasma, cryoprecipitate, and PLTs in the MTPs were 6, 4, 1, and 1, respectively.62 We are not aware of any studies that have examined the availability of a MTP in nonacademic units.
Fixed-Ratio Transfusion Approaches
Recommendations for using fixed ratios of plasma:RBC in obstetrics originate from the nonobstetric setting. In recent years, experts in obstetric hemostasis have questioned whether the use of fixed-ratio transfusions from nonobstetric settings is applicable to the management of PPH.15,20,32 These concerns were highlighted by the D-A-CH and the expert panel. However, no alternative approaches were discussed by these societies. In the trauma setting, the use of ratio-based transfusion with coagulation test-guided care has been advocated.63 In the obstetric setting, there have been calls for comparative effectiveness studies to compare maternal outcomes for women managed with fixed ratios of plasma:RBC versus goal-directed approaches using laboratory and/or point-of-care measurement of coagulation parameters.64
Decision to Transfuse in Patients With Acute Anemia After PPH
Several societies (RCOG, D-A-CH, ASA, and AABB) recommend RBC transfusion according to a threshold or nadir hemoglobin value. It is uncertain whether this guidance applies to the period of active blood loss or after arrest of bleeding. Among nonobstetric, nonbleeding (“stable”) anemic patients, liberal transfusion approaches do not reduce rates of mortality or morbidity compared with restrictive approaches.65,66 Furthermore, evidence suggests that adopting a restrictive transfusion approach either within single institutions or health care systems can decrease the number of RBCs transfused per patient and potentially improve patient outcomes (by reducing mortality rate and length of hospital stay).67–70 These results have not been confirmed in the obstetric setting. In a randomized, nonblinded study to assess the effect of RBC transfusion versus no intervention on the maternal quality of life among women with PPH and early postpartum anemia (Hb 4.8–7.9 g/dL 12- to 24-hours postpartum), Prick et al71 did not demonstrate non-inferiority with the non-RBC-based approach. However, on postpartum day 3, the authors noted that women in the no intervention group only had a 0.78 higher mean physical fatigue score compared with those receiving RBC (physical fatigue scores range from 4 to 20; higher scores indicating more fatigue). These data should not discount the need to consider treatment for postpartum anemia, especially as important maternal morbidities are associated with this condition, including depression,72–74 fatigue,75 and impaired cognition.76 These morbidities can negatively impact maternal-child bonding and the mother’s ability to provide newborn care.77 There is also an underappreciation of the high prevalence of postpartum anemia. In the United States, Bodnar et al78 reported that 19% women in low-income groups had a hemoglobin <12 g/dL between 4 and 26 weeks postpartum. Iron replacement therapy has been recommended for the treatment of mild to moderate iron deficiency anemia.79 With anemia detection, diagnosis, and treatment recognized a key facet of PBM,80 obstetric societies may need to consider whether postpartum anemia screening should be incorporated into PBM guidelines.
Laboratory Indices and Point-of-Care Testing
Many societies included laboratory indices (PT, APTT, international normalized ratio [INR], fibrinogen) as transfusion triggers or “therapeutic goals.” However, the usefulness of PT, APTT, and INR as triggers for transfusion therapy has been called into question.32,81 There is a lack of high-quality evidence to substantiate whether a trigger of ≥1.5-fold prolongation of APTT/PT or INR is helpful for diagnosing coagulopathic bleeding or to indicate whether supportive therapy should be given.81 It is worth noting that the PT and APTT can often remain normal in the face of severe obstetric bleeding.32,82–84 Furthermore, the onset and severity of coagulopathy may vary according to the etiology of obstetric hemorrhage. In contrast, recent evidence suggests that, during the early stage of bleeding, a low fibrinogen level (<200 mg/dL) can be an important marker for severe PPH and the need for advanced surgical/medical intervention for PPH management.85–87 In general, obstetric societies’ recommendations did not account for new data on fibrinogen changes during PPH. The expert panel was the only obstetric group recommending supplementation if fibrinogen <200 mg/dL, whereas other obstetric societies recommended a lower threshold (100 mg/dL).
Several societies recommended using point-of-care devices (TEG, ROTEM) to assess the maternal coagulation profile. The application of these technologies in the obstetric setting has been promoted by experts in obstetric hemostasis.33,88 Benefits of these devices include quicker turnaround times compared with standard laboratory tests, and identification of specific coagulation defects, including functional fibrinogen deficiency and fibrinolysis. Point-of-care testing and laboratory tests of coagulation can be incorporated into an integrated, goal-directed approach for transfusion decision making.32,89 However, these tests are not available in most labor and delivery units. In addition to equipment costs, these devices require regular calibration, and TEG/ROTEM data interpretation requires education.
Pharmacological Treatment: Antifibrinolytics, rFVIIa, and Fibrinogen Concentrate
Three obstetric societies provided recommendations for antifibrinolytics, whereas 1 society (RCOG) recommended against its use. Several meta-analyses90,91 and a systematic review92 suggest that tranexamic acid, given either prophylactically or therapeutically, results only in modest, nonclinically significant reductions in blood loss (149 mL and 92 mL, respectively) compared with standard approaches. Of note, the majority of studies assessed the effect of tranexamic acid on patients undergoing elective cesarean delivery. The authors of these systematic reviews expressed concern about the methodological quality of investigations assessing tranexamic acid efficacy. The results of the World Maternal Antifibrinolytic Trial (WOMAN) study, an international study randomizing 20,000 women who experience PPH after vaginal or cesarean delivery to 1 to 2 g tranexamic acid versus placebo, may provide new data on whether tranexamic acid reduces severe hemorrhage-related morbidity or death.93
Because of the dearth of high-quality evidence on rFVIIa, societies’ recommendations are predominantly based on expert opinion. This may explain the variation in recommendations for rFVIIa across obstetric societies. Anecdotal obstetric reports or registry data suggest that rFVIIa may be a viable therapeutic option for patients with severe refractory obstetric hemorrhage,94–97 but have also described severe thrombotic complications.
Data on the efficacy of fibrinogen concentrate are relatively limited. In a multicenter, randomized study, administration of fibrinogen concentrate in the early stage of PPH did not reduce RBC requirements compared with placebo.98 However, only 2.2% patients had a fibrinogen level <200 mg/dL at the time of study enrollment. Data from ongoing studies will provide important information for determining whether fibrinogen concentrate improves outcomes for women with severe PPH.99,100
We acknowledge that our review has limitations. We did not review PBM recommendations published by all obstetric, anesthetic, hematology societies, nor national agencies and consensus groups. For example, the Subcommittee on Women’s Health Issues of the International Society of Thrombosis and Hemostasis recently published guidelines on the management of coagulopathy associated with PPH.101 We elected to exclude these guidelines because PBM guidelines for patients without coagulopathy were not discussed. Although a bundle of care is a structured approach for improving processes of care and patient outcomes,102 the content of a bundle and clinical practice guidelines comprise evidence-based practices. Therefore, we believe that the PBM recommendations in the NMPS bundle were worthy of comparison with those of national obstetric societies. We cannot determine the extent to which clinicians follow PBM and transfusion guidelines for PPH management. In the IOM report (Clinical Practice Guidelines We Can Trust),35 it is possible that easy access to clinical practice guidelines may be out of reach for some clinicians. In addition, there may be large gaps between recommended care and delivered care. Clinical decision support systems, embedded in anesthesia or electronic medical record systems, may provide a vehicle for improving rates of clinician adherence to clinical practice guidelines.103 Last, we acknowledge that we did not perform a quantitative assessment of guideline quality using validated instruments, such as The Appraisal of Guidelines for Research & Evaluation (AGREE II).104 These tools can be used by policy makers and health care providers to help make decisions about which guidelines should be recommended for clinical use. Our goal was to present PBM and transfusion recommendations, sourced from obstetric and nonobstetric societies’ guidelines, to allow side-by-side comparisons of content material.
In this review of current professional society guidelines, we observed inconsistencies in obstetric and nonobstetric societies’ PBM and transfusion recommendations for PPH management. These inconsistencies may hinder how clinicians provide quality care to patients with severe PPH. We advise obstetric, anesthesiology, and transfusion societies to form interdisciplinary partnerships to achieve better consensus for these recommendations. Applying IOM standards may also improve how future PBM guidelines are developed.35 These include standardizing (i) how evidence is evaluated (including relative benefit/harm and cost-effectiveness of individual interventions), and (ii) the strength of recommendations and how these recommendations are articulated. Evidence that is extrapolated from nonobstetric populations should be clearly identified, with the goal to develop a robust context-specific evidence base for obstetric hemorrhage. Last, societies should fully disclose conflicts of interest for guideline authors, obtain greater patient and public involvement, perform external review, and more regularly update guidelines as new practice-changing evidence emerges.
Name: Ruth Shaylor, BMBS, BMedSci.
Contribution: This author helped with the acquisition, analysis, and interpretation of data, helped draft the work and revise it critically, and approved the final version of the manuscript.
Name: Carolyn F. Weiniger, MBChB.
Contribution: This author helped design the work, helped with the acquisition, analysis, and interpretation of data, helped draft the work and revise it critically, and approved the final version of the manuscript.
Name: Naola Austin, MD.
Contribution: This author helped with the acquisition and analysis of data, helped draft the manuscript and revise it critically, and approved the final version of the manuscript.
Name: Alexander Tzabazis, MD.
Contribution: This author helped with the acquisition, analysis, and interpretation of data, helped revise the draft critically, and approved the final manuscript.
Name: Aryeh Shander, MD, FCCM, FCCP.
Contribution: This author helped with the interpretation of data, helped revise the draft critically, and approved the final manuscript.
Name: Lawrence T. Goodnough, MD.
Contribution: This author helped with the interpretation of data, helped revise the draft critically, and approved the final manuscript.
Name: Alexander J. Butwick, MBBS, FRCA, MS.
Contribution: This author helped with the conception of the work and acquisition, analysis, and interpretation of data, helped draft the work and revise it critically, and approved the final manuscript.
This manuscript was handled by: Jill Mhyre, MD.
The authors acknowledge the input of Ms Neachama Rothschild, BSc, who assisted in reviewing the D-A-CH guidelines.
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