Efficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage.

Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03-0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06-5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03-1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Prophylactic radiologic interventions to reduce postpartum hemorrhage in women with risk factors for placenta accreta spectrum disorder: a nationwide cohort study.

OBJECTIVE: To quantify the association between prophylactic radiologic interventions and perioperative blood loss in women with risk factors for placenta accreta spectrum disorder (PAS). METHODS: We conducted a retrospective nationwide cohort study of women with risk factors for placenta accreta spectrum disorder who underwent planned cesarean section in 69 Dutch hospitals between 2008 and 2013. All women had two risk factors for PAS: placenta previa/anterior low-lying placenta and a history of cesarean section(s). Women with and without ultrasonographic signs of PAS were studied as two separate groups. We compared the total blood loss of women with prophylactic radiologic interventions, defined as preoperative placement of balloon catheters or sheaths in the internal iliac or uterine arteries, with that of a control group consisting of women without prophylactic radiologic interventions using multivariable regression. We evaluated maternal morbidity by the number of red blood cell (RBC) units transfused within 24 h following childbirth (categories: 0, 1-3, >4), duration of hospital admission, and need for intensive care unit (ICU) admission. RESULTS: A total of 350 women with placenta previa/anterior low-lying placenta and history of cesarean section(s) were included: 289 with normal ultrasonography, of whom 21 received prophylactic radiologic intervention, and 61 had abnormal ultrasonography, of whom 22 received prophylactic intervention. Among women with normal ultrasonography without prophylactic intervention (n = 268), the median blood loss was 725 mL (interquartile range (IQR) 500-1500) vs. 1000 mL (IQR 550-1750) in women with intervention (n = 21); the adjusted difference in blood loss was 9 mL (95% confidence interval (CI) -315-513), p = .97). Among women with abnormal ultrasonography, those without prophylactic intervention (n = 39) had a median blood loss of 2500 mL (IQR 1200-5000) vs. 1750 mL (IQR 775-4000) in women with intervention (n = 22); the adjusted difference in blood loss was -1141 mL (95% CI -1694- -219, p = .02). Results of outcomes on maternal morbidity were comparable among women with and without prophylactic intervention. CONCLUSION: These findings suggest that prophylactic radiologic interventions prior to planned cesarean section may help to limit perioperative blood loss in women with clear signs of placenta accreta spectrum disorder on ultrasonography, but there was no evidence of a difference within the subgroup without such ultrasonographic signs. The use of these interventions should be discussed in a multidisciplinary shared decision-making process, including discussions of potential benefits and possible complications. TRIAL REGISTRATION: Netherlands Trial Registry, https://onderzoekmetmensen.nl/en/trial/28238, identifier NL4210 (NTR4363).

Clinical value of early assessment of hyperfibrinolysis by rotational thromboelastometry during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: Coagulopathy may be the result of hyperfibrinolysis and could exacerbate bleeding following childbirth. Timely recognition of hyperfibrinolysis during the earliest stages of postpartum hemorrhage could identify women at risk of more severe blood loss who may benefit from targeted anti-fibrinolytic therapy. Rotational thromboelastometry (ROTEM® ) is a point-of-care test that could detect hyperfibrinolysis. The aim of this study was to evaluate whether early assessment of hyperfibrinolysis by ROTEM during postpartum hemorrhage could predict progression to severe postpartum hemorrhage. MATERIAL AND METHODS: During a prospective cohort study in the Netherlands among women with postpartum hemorrhage (total blood loss at least 1000 ml within 24 h after childbirth) ROTEM measurements were performed following 800-1500 ml of blood loss. Hyperfibrinolysis was defined as an enzymatic fibrinolysis index (ROTEM EXTEM maximum clot lysis [ML] minus the ROTEM APTEM ML) above 15%. Severe postpartum hemorrhage was defined as a composite end point of total blood loss greater than 2000 ml, transfusion of four or more units of packed cells, and/or need for an invasive intervention. The predictive value of hyperfibrinolysis for progression to severe postpartum hemorrhage was assessed by area under the receiver operating curve (AUC) and positive and negative predictive values. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149472). RESULTS: Of 390 women included, 82 (21%) had severe postpartum hemorrhage. Four (1%) women had thromboelastometric evidence of hyperfibrinolysis, of whom two developed severe postpartum hemorrhage. The AUC for enzymatic fibrinolysis index more than 15% for progression to severe postpartum hemorrhage was 0.47 (95% CI 0.40-0.54). Positive and negative predictive values for this index were 50.0% (95% CI 6.8-93.2) and 79.3% (95% CI 74.9-83.2), respectively. CONCLUSIONS: Thromboelastometric evidence of hyperfibrinolysis was rare in women with postpartum hemorrhage when assessed between 800 and 1500 ml of blood loss. The clinical predictive value of viscoelastometric point-of-care testing for hyperfibrinolysis for progression to severe postpartum hemorrhage during early postpartum hemorrhage is limited.

Clinical value of early viscoelastometric point-of-care testing during postpartum hemorrhage for the prediction of severity of bleeding: A multicenter prospective cohort study in the Netherlands.

INTRODUCTION: To evaluate rotational fibrin-based thromboelastometry (ROTEM® FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to severe postpartum hemorrhage, and compare its predictive value with that of fibrinogen. MATERIAL AND METHODS: Prospective cohort study in the Netherlands including women with 800-1500 ml of blood loss within 24 h following birth. Blood loss was quantitatively measured by weighing blood-soaked items and using a fluid collector bag in the operating room. Both FIBTEM A5 values and fibrinogen concentrations (Clauss method) were measured between 800 and 1500  ml of blood loss. Predictive accuracy of both biomarkers for the progression to severe postpartum hemorrhage was measured by area under the receiver operating curves (AUC). Severe postpartum hemorrhage was defined as a composite endpoint of (1) total blood loss >2000 ml, (2) transfusion of ≥4 packed cells, and/or (3) need for an invasive intervention to cease bleeding. RESULTS: Of the 391 women included, 72 (18%) developed severe postpartum hemorrhage. Median (IQR) volume of blood loss at blood sampling was 1100 ml (1000-1300) with a median (interquartile range [IQR]) fibrinogen concentration of 3.9 g/L (3.4-4.6) and FIBTEM A5 value of 17 mm (13-20). The AUC for progression to severe postpartum hemorrhage was 0.53 (95% confidence interval [CI] 0.46-0.61) for FIBTEM A5 and 0.58 (95% CI 0.50-0.65) for fibrinogen. Positive predictive values for progression to severe postpartum hemorrhage for FIBTEM A5 ≤12 mm was 22.5% (95% CI 14-33) and 50% (95% CI 25-75) for fibrinogen ≤2 g/L. CONCLUSIONS: The predictive value of FIBTEM A5 compared to fibrinogen concentrations measured between 800 and 1500 ml of blood loss following childbirth was poor to discriminate between women with and without progression towards severe postpartum hemorrhage.

Association of Timing of Plasma Transfusion With Adverse Maternal Outcomes in Women With Persistent Postpartum Hemorrhage.

Importance: Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes. Objective: To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH. Design, Setting, and Participants: This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019. Exposures: Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion. Main Outcomes and Measures: Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization. Results: This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results. Conclusions and Relevance: In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH.

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study.

BACKGROUND: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. METHODS: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. RESULTS: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. CONCLUSION: The definition persistent postpartum haemorrhage identified women with severe postpartum haemorrhage at an early stage of haemorrhage, unlike definitions based on blood transfusion. It also captured a large majority of adverse maternal outcomes, almost as large as the definition of ≥1 L blood loss, which is commonly applied as a definition of postpartum haemorrhage rather than severe haemorrhage.

Comparison of outcome between intrauterine balloon tamponade and uterine artery embolization in the management of persistent postpartum hemorrhage: A propensity score-matched cohort study.

INTRODUCTION: The aim of this study was to compare the outcomes of women who were initially managed by intrauterine balloon tamponade or uterine artery embolization because of persistent postpartum hemorrhage demanding an immediate intervention to control bleeding. MATERIAL AND METHODS: Propensity score-matched cohort study including women who had intrauterine balloon tamponade or uterine artery embolization as initial management strategy to control persistent postpartum hemorrhage, that is, refractory to first-line therapy combined with at least one uterotonic agent. The primary outcome measure was a composite of peripartum hysterectomy and/or maternal mortality. Secondary outcomes measures were total volume of blood loss and total number of packed red blood cells transfused. RESULTS: Our 1:1 propensity score-matched cohort comprised of 50 women who had intrauterine balloon tamponade and 50 women who underwent uterine artery embolization at a blood loss between 1000 and 7000 mL. There was no statistically significant difference in the hysterectomy risk between the two groups (n = 6 in each group, odds ratio [OR] 1.00, 95% confidence interval [CI] .30-3.34), in total volume of blood loss (median 4500 mL, interquartile range [IQR] 3600-5400) for balloon vs 4000 mL (IQR 3250-5000) for embolization, P = 0.382) or in total units of packed red blood cells transfused (median 7 (IQR 5-10) for balloon vs 6 [IQR 4-9] for embolization, P = 0.319). Fifteen women (30%) who were initially managed by an intrauterine balloon still underwent uterine artery embolization, of whom one had an embolization-related thrombo-embolic event. Maternal mortality occurred in neither of the intervention groups. CONCLUSIONS: No difference in the risk of peripartum hysterectomy and/or maternal death was observed between women who had intrauterine balloon tamponade and women who underwent uterine artery embolization as an initial management for persistent postpartum hemorrhage. Although this study was underpowered to demonstrate equivalence, our study design provides a framework for future research in which intrauterine balloon tamponade may prove to be a suitable intervention of first choice in the management of persistent postpartum hemorrhage.

Predictive value of a bleeding score for postpartum hemorrhage.

BACKGROUND: A reliable screening tool that could contribute to the identification of women with an increased risk of postpartum hemorrhage would be of great clinical significance. OBJECTIVES: The aim of this study was to examine the added predictive value of a bleeding assessment tool for postpartum hemorrhage exceeding 1000 mL. PATIENTS/METHODS: Prospective two-center cohort study among 1147 pregnant women visiting the outpatient clinic or the maternity ward who completed a bleeding assessment tool prior to birth. The condensed MCMDM-1VWD bleeding assessment tool was adjusted to a questionnaire that could be used as a self-assessment bleeding tool. A score of ≥4 was considered to be abnormal. RESULTS: In the 1147 pregnant women in our cohort, bleeding scores ranged from -3 to 13, with a median of 1 (IQR -1 to 3); 197 (17%) women developed postpartum hemorrhage. Among women with a history of postpartum hemorrhage 29% developed postpartum hemorrhage. Among 147 women with an abnormal bleeding score (≥4), 27 (18%) developed postpartum hemorrhage, whereas the remaining 170 cases of postpartum hemorrhage had a normal bleeding score. Despite the high incidence of postpartum hemorrhage, the ability of the bleeding score to predict postpartum hemorrhage was poor: area under receiver operating curve 0.53 (95% CI 0.49-0.58) for postpartum hemorrhage (PPH) ≥1000 mL. CONCLUSIONS: A history of significant postpartum hemorrhage was associated with an increased risk of subsequent postpartum hemorrhage. However, screening with a bleeding assessment tool did not help to discriminate women who will develop postpartum hemorrhage from women who will not.

Fluid resuscitation during persistent postpartum haemorrhage and maternal outcome: A nationwide cohort study.

OBJECTIVE: To determine the association between increasing volumes of crystalloids and colloids administered before transfusion of packed red blood cells in women with persistent postpartum haemorrhage and adverse maternal outcomes. STUDY DESIGN: Retrospective cohort study in the Netherlands. Women with persistent postpartum haemorrhage and known clear fluids volume for resuscitation were included. Women who received ≤2 L of clear fluids were the reference group. We determined the effect of every additional litre of clear fluids on total blood loss, severe maternal morbidity and mortality. Results were adjusted for patient and bleeding characteristics. RESULTS: Of the 883 included women, 199 received ≤2 L of clear fluids. Median blood loss for the reference group was 2.9 L (interquartile range 2.2-3.4). Adjusted mean difference in blood loss compared with the reference group was 0.2 L (95% confidence interval -0.1 to 0.5) for women in the >2 to ≤3 L, 0.4 L (0.1-0.7) for the >3 to ≤4 L category, 0.6 L (0.5-0.7) for the >4 to ≤5 L category, and 1.9 L (1.5-2.3) for the >5 to ≤7 L category. Adjusted odds ratios for adverse maternal outcomes were 1.0 (0.7-1.6), 1.2 (0.8-1.9), 1.8 (1.1-3.1) and 4.4 (2.6-7.5) for women in the 2 to ≤3 L category, >3 to ≤4 L, >4 to ≤5 L, and >5 to ≤7 L volume categories respectively. Results were similar in strata of different severities of bleeding. CONCLUSION: Clear fluids volume >4 L was independently associated with adverse maternal outcome in women with persistent postpartum haemorrhage.

Comparison of thromboelastometry by ROTEM® Delta and ROTEM® Sigma in women with postpartum haemorrhage.

Haemostatic treatment in women experiencing postpartum haemorrhage is increasingly based on point-of-care devices such as ROTEM® thromboelastometry. Recently, a fully automated successor of the ROTEM® Delta device, the ROTEM® Sigma was introduced. To determine whether these devices provide similar results, we compared ROTEM® parameters using the ROTEM® Delta and Sigma devices in women experiencing postpartum haemorrhage. Prospective observational cohort study of 23 women experiencing postpartum haemorrhage. ROTEM® INTEM, EXTEM, FIBTEM and APTEM measurements handled by the ROTEM® Delta and Sigma devices were compared. ROTEM® FIBTEM values were also related to Clauss fibrinogen values. A correlation of Spearman's r (rs) varying between 0.76 and 0.95 was displayed between clot firmness measured in millimeters at 5 (A5), 10 (A10) and 20 (A20) minutes after start of clot formation measured by EXTEM, INTEM and APTEM assays executed on both devices; A5, A10 and A20 of FIBTEM correlated less well (rS between 0.71 and 0.74), especially after five and ten minutes. Correlation between both devices regarding clotting time (CT) was poor. The observed correlation between levels of Clauss fibrinogen and FIBTEM A5 was rs = 0.70, (95% confidence interval (CI): 0.38 to 0.87) for Delta and rs = 0.85, (CI 0.65 to 0.94) for Sigma. A5, A10 and A20 measured in EXTEM, INTEM and APTEM obtained from ROTEM® Delta and Sigma devices were similar. EXTEM, FIBTEM and APTEM CT values from both devices showed no correlation. Substantial variation was found between FIBTEM assays of the devices. Consequently, results of FIBTEM assays should always be interpreted in the context of device-specific reference values. Correlation with Clauss fibrinogen was better in the ROTEM® Sigma device.

Women receiving massive transfusion due to postpartum hemorrhage: A comparison over time between two nationwide cohort studies.

INTRODUCTION: Incidence of massive transfusion after birth was high in the Netherlands between 2004 and 2006 compared with other high-income countries. This study investigated incidence, causes, management and outcome of women receiving massive transfusion due to postpartum hemorrhage in the Netherlands in more recent years. MATERIAL AND METHODS: Data for all pregnant women who received eight or more units of packed red blood cells from a gestational age of 20 weeks and within the first 24 hours after childbirth, during 2011 and 2012, were obtained from a nationwide retrospective cohort study, including 61 hospitals with a maternity unit in the Netherlands. RESULTS: Incidence of massive transfusion due to postpartum hemorrhage decreased to 65 per 100 000 births (95% CI 56-75) between 2011 and 2012, from 91 per 100 000 births (95% CI 81-101) between 2004 and 2006, while median blood loss increased from 4500 mL (interquartile range 3250-6000) to 6000 mL (interquartile range 4500-8000). Uterine atony remained the leading cause of hemorrhage. Thirty percent (53/176) underwent peripartum hysterectomy between 2011 and 2012, compared with 25% (83/327) between 2004 and 2006. Case fatality rate for women who received massive transfusion due to postpartum hemorrhage was 2.3% (4/176) between 2011 and 2012, compared with 0.9% (3/327) between 2004 and 2006. CONCLUSIONS: The incidence of postpartum hemorrhage with massive transfusion decreased in the Netherlands between both time frames, but remained an important cause of maternal mortality and morbidity, including peripartum hysterectomy. National surveillance of maternal morbidity and mortality due to postpartum hemorrhage through an improved and continuous registration with confidential enquiries may lead to the identification of clear improvements of maternal care.

Association between fluid management and dilutional coagulopathy in severe postpartum haemorrhage: a nationwide retrospective cohort study.

BACKGROUND: The view that 2 l of crystalloid and 1.5 l of colloid can be infused while awaiting compatible blood for patients with major postpartum haemorrhage is based on expert opinion documents. We describe real-world changes in levels of coagulation parameters after the administration of different volumes of clear fluids to women suffering from major postpartum haemorrhage. METHODS: We performed a nationwide retrospective cohort study in the Netherlands among 1038 women experiencing severe postpartum haemorrhage who had received at least four units of red cells or fresh frozen plasma or platelets in addition to red cells. The volume of clear fluids administered before the time of blood sampling was classified into three fluid administration strategies, based on the RCOG guideline: < 2 L, 2-3.5 L and > 3.5 L. Outcomes included haemoglobin, haematocrit, platelet count, fibrinogen, aPTT and PT levels. RESULTS: Haemoglobin, haematocrit, platelet count, fibrinogen and aPTT were associated with volumes of clear fluids, which was most pronounced early during the course of postpartum haemorrhage. During the earliest phases of postpartum haemorrhage median haemoglobin level was 10.1 g/dl (IQR 8.5-11.6) among the women who received < 2 L clear fluids and 8.1 g/dl (IQR 7.1-8.4) among women who received > 3.5 L of clear fluids; similarly median platelet counts were 181 × 109/litre (IQR 131-239) and 89 × 109/litre (IQR 84-135), aPTT 29 s (IQR 27-33) and 38 s (IQR 35-55) and fibrinogen 3.9 g/L (IQR 2.5-5.2) and 1.6 g/L (IQR 1.3-2.1). CONCLUSIONS: In this large cohort of women with severe postpartum haemorrhage, administration of larger volumes of clear fluids was associated with more severe deterioration of coagulation parameters corresponding to dilution. Our findings provide thus far the best available evidence to support expert opinion-based guidelines recommending restrictive fluid resuscitation in women experiencing postpartum haemorrhage. TRIAL REGISTRATION: Netherlands Trial Register ( NTR4079 ), registration date July 17, 2013.

Coagulation parameters during the course of severe postpartum hemorrhage: a nationwide retrospective cohort study.

We describe the pattern of change in coagulation parameters during the course of severe postpartum hemorrhage in a retrospective cohort study among 1312 women experiencing severe postpartum hemorrhage necessitating blood transfusion. Levels of hemoglobin, hematocrit, platelet count, fibrinogen, activated partial thromboplastin time (aPTT) and prothrombin time (PT) per categorized volume of blood loss during severe postpartum hemorrhage were described and compared between women with and without the composite adverse outcome. Need for surgical intervention, severe acute maternal morbidity, and maternal mortality were jointly considered the composite adverse outcome. Of the 1312 women, 463 (35%) developed the composite adverse outcome. The incidence of a fibrinogen level <2 g/L was 26% (342 per 1312). Low fibrinogen and prolonged aPTT during the first 2 L of hemorrhage were associated with a subsequent composite adverse outcome; median fibrinogen and aPTT among women with and without the composite end point after 1.5 to 2 L of hemorrhage were 1.5 g/L (interquartile range [IQR], 1.0-1.9) vs 2.7 g/L (IQR, 1.9-3.4) and 39 s (IQR, 30-47) vs 32 s (IQR, 28-36), respectively. PT and platelet count as assessed during the first 2 L of hemorrhage were not associated with morbidity or mortality. Our results suggest that detection of low levels of fibrinogen and elevated aPTT levels during early postpartum hemorrhage can contribute to the identification of women that may benefit from targeted hemostatic treatment. Essential in this identification process is the moment of reaching a level of fibrinogen of <2 g/L during the course of postpartum hemorrhage.

The effect of tranexamic acid on blood loss and maternal outcome in the treatment of persistent postpartum hemorrhage: A nationwide retrospective cohort study.

BACKGROUND: Recent results show a protective effect of tranexamic acid on death due to bleeding in patients with postpartum hemorrhage in low- and middle-resource countries. We quantify the association between early administration of tranexamic acid compared to late or no administration and severe acute maternal morbidity and blood loss among women suffering from persistent severe postpartum hemorrhage in a high-income country. METHODS AND FINDINGS: We performed a nationwide retrospective cohort study in 61 hospitals in the Netherlands. The study population consisted of 1260 women with persistent postpartum hemorrhage who had received at least four units of red cells, or fresh frozen plasma or platelets in addition to red cells. A review of medical records was performed and cross-referenced with blood bank data. The composite endpoint comprised maternal morbidity (hysterectomy, ligation of the uterine arteries, emergency B-Lynch suture, arterial embolization or admission into an intensive care unit) and mortality. RESULTS: 247 women received early tranexamic acid treatment. After adjustment for confounding, odds ratio for the composite endpoint for early tranexamic acid (n = 247) versus no/late tranexamic acid (n = 984) was 0.92 (95% confidence interval (CI) 0.66 to 1.27). Propensity matched analysis confirmed the absence of a difference between women with and without tranexamic acid. Blood loss after administration of first line therapy did not differ significantly between the two groups (adjusted difference -177 mL, CI -509.4 to +155.0). CONCLUSIONS: Our findings suggest that in a high-resource country the effect of tranexamic acid on both blood loss and the combined endpoint of maternal mortality and morbidity may be disappointing.

Incidence, management and outcome of women requiring massive transfusion after childbirth in the Netherlands: secondary analysis of a nationwide cohort study between 2004 and 2006.

BACKGROUND: Postpartum hemorrhage remains the leading cause of maternal morbidity and mortality worldwide. Few population-based studies have examined the epidemiology of massive transfusion for postpartum hemorrhage. The aim of this study was to determine the incidence, management, and outcomes of women with postpartum hemorrhage who required massive transfusion in the Netherlands between 2004 and 2006. METHODS: Data for all women from a gestational age of 20 weeks onwards who had postpartum hemorrhage requiring eight or more red blood cell concentrates were obtained from a nationwide population-based cohort study including all 98 hospitals with a maternity unit in the Netherlands. RESULTS: Three hundred twenty-seven women who had postpartum hemorrhage requiring massive transfusion were identified (massive transfusion rate 91 per 100,000 deliveries (95% confidence interval: 81-101)). The median blood loss was 4500 mL (interquartile range 3250-6000 mL) and the median number of red blood cell concentrates transfused was 11 units (interquartile range 9-16 units). Among women receiving massive transfusion, the most common cause of hemorrhage was uterine atony. Eighty-three women (25%) underwent hysterectomy, 227 (69%) were admitted to an intensive care unit, and three women died (case fatality rate 0,9%). CONCLUSION: The number of women in the Netherlands who had postpartum hemorrhage treated with massive transfusion was relatively high compared to other comparable settings. Evidence-based uniform management guidelines are necessary.

Polypectomy in premenopausal women with abnormal uterine bleeding: effectiveness of hysteroscopic removal.

STUDY OBJECTIVE: To estimate the effectiveness of hysteroscopic polypectomy in premenopausal women with abnormal uterine bleeding and to identify prognostic factors for persistence or recurrence of symptoms after polypectomy. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: University teaching hospital. PATIENTS: Premenopausal women with abnormal uterine bleeding. INTERVENTION: Hysteroscopic polypectomy, regardless of whether combined with endometrial ablation or insertion of a levonorgestrel-releasing intrauterine device. MEASUREMENTS AND MAIN RESULTS: Seventy-eight consecutive patients met the inclusion criteria and were followed over time. Data were retrieved from medical records or from additional questionnaires sent to the patients. Failure of treatment was defined as persistence or recurrence of abnormal uterine bleeding after polypectomy, requiring further treatment. The mean age was 44.2 years (SD 5.2, 95% CI 33.9-54.4 years). Intervention-free survival after polypectomy, as calculated by Kaplan-Meier survival analysis, was 41.1% (SE 8.3%, 95% CI 24.8%-57.4%) after 4 years for patients who underwent only hysteroscopic polypectomy and 54.7% (SE 13.6%, 95% CI 28.0%-81.4%) for patients who underwent a polypectomy combined with endometrial ablation or insertion of a levonorgestrel-releasing intrauterine device (p = .08). Cox regression analyses revealed no statistically significant predictors for persistence or recurrence of symptoms after polypectomy. CONCLUSION: Nearly 60% of patients required further treatment for persistence or recurrence of abnormal uterine bleeding 4 years after hysteroscopic polypectomy. Although not significant, outcome of treatment tended to improve by combining polypectomy with either an endometrial ablation or insertion of a levonorgestrel-releasing intrauterine device.